Lyme disease, or borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia.[1] Borrelia burgdorferi is the predominant cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii are implicated in most European cases.
Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Borrelia is transmitted to humans by the bite of infected hard ticks belonging to several species of the genus Ixodes.[2] Early manifestations of infection may include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. Left untreated, late manifestations involving the joints, heart, and nervous system can occur. In a majority of cases, symptoms can be eliminated with antibiotics, especially if diagnosis and treatment occur early in the course of illness. Late, delayed, or inadequate treatment can lead to late manifestations of Lyme disease which can be disabling and difficult to treat.
Some groups have argued that "chronic" Lyme disease is responsible for a range of medically unexplained symptoms beyond the objectively recognized manifestations of late Lyme disease, and that long-term antibiotic treatment is warranted in such cases.[3] However, a series of randomized controlled trials found no significant benefit from prolonged antibiotic treatment in such patients,[4][5][6] and most expert groups including the Infectious Diseases Society of America and the American Academy of Neurology have found that existing scientific evidence does not support a role for Borrelia nor ongoing antibiotic treatment in such cases.[7][8]
Symptoms
Lyme disease can affect multiple body systems, producing a range of potential symptoms. Not all patients with Lyme disease will have all symptoms, and many of the symptoms are not specific to Lyme disease but can occur in other diseases as well. The incubation period from infection to the onset of symptoms is usually 1–2 weeks, but can be much shorter (days), or much longer (months to years). Symptoms most often occur from May through September because the nymphal stage of the tick is responsible for most cases.[9] Asymptomatic infection exists but is found in less than 7% of infected individuals in the United States.[10] Asymptomatic infection may be much more common among those infected in Europe.[11]
Stage 1 – Early localized infection
Common bullseye rash pattern associated with Lyme Disease.
Common bullseye rash pattern associated with Lyme Disease.
Characteristic "bulls-eye"-like rash caused by Lyme disease.
Characteristic "bulls-eye"-like rash caused by Lyme disease.
The classic sign of early local infection is a circular, outwardly expanding rash called erythema chronicum migrans (also erythema migrans or EM), which occurs at the site of the tick bite 3 to 32 days after being bitten.[12] The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated; the outer edge remains red; and the portion in between clears – giving the appearance of a bullseye. However, the partial clearing is uncommon, and thus a true bullseye occurs in as few as 9% of cases.[13]
Erythema migrans is thought to occur in about 80% of infected patients.[12]
Lyme disease can progress to later stages even in patients who do not develop a rash.[14]
Stage 2 – Early disseminated infection
Within days to weeks after the onset of local infection, the borrelia bacteria may begin to spread through the bloodstream. Erythema migrans may develop at sites across the body that bear no relation to the original tick bite.[15] Other discrete symptoms include loss of muscle tone on one or both sides of the face (called facial or Bell's palsy), severe headaches and neck stiffness, shooting pains that may interfere with sleep, heart palpitations and dizziness caused by changes in heartbeat, and migrating joint pains. Some of these symptoms may resolve, even without treatment.[citation needed]
Stage 3 – Late persistent infection
After several months, untreated or inadequately treated patients may go on to develop severe and chronic symptoms affecting many organs of the body including the brain, nerves, eyes, joints and heart. Shooting pains, numbness or tingling in the hands or feet, problems with concentration and short term memory, severe weakness, vision problems, intolerance to sound and touch, Vertigo, back pain, heart block, psychiatric disorders, and swelling of joints are just some of the myriad disabling symptoms that can occur.
Other less common findings in acute Lyme disease include cardiac manifestations (up to 10% of patients may have cardiac manifestations including heart block and palpitations[16]), and neurologic symptoms (neuroborreliosis may occur in up to 18%[16]). In addition, simple altered mental status as the sole presenting symptom has been reported in early neuroborreliosis.[17] Patients have been known to get Baker's cysts.
Chronic symptoms
Cases may progress to a chronic form most commonly characterized by meningoencephalitis, cardiac inflammation (myocarditis), frank arthritis, and fatigue.[1] Chronic Lyme disease can have a multitude of symptoms affecting numerous physiological systems: the symptoms appear heterogeneous in the affected population, which may be caused by innate immunity or variations in Borrelia bacteria. Late symptoms of Lyme disease can appear months or years after initial infection and often progress in cumulative fashion over time. Neuropsychiatric symptoms often develop much later in the disease progression, much like tertiary neurosyphilis.
In addition to the acute symptoms, chronic Lyme disease can be manifested by a wide-range of neurological disorders, either central or peripheral, including encephalitis or encephalomyelitis, muscle twitching, heightened sensitivity to touch, sound and light, paralysis[18] polyneuropathy or paresthesia, and vestibular symptoms or other otolaryngologic symptoms,[19][20] among others. Neuropsychiatric disturbances can occur (possibly from a low-level encephalitis), which may lead to symptoms of memory loss, sleep disturbances, or changes in mood or affect.[1] In rare cases, frank psychosis has been attributed to chronic Lyme disease effects, including mis-diagnoses of schizophrenia and bipolar disorder. Panic attack and anxiety can occur, also delusional behavior, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome similar to what was seen in the past in the prodromal or early stages of general paresis.[21][22]
Cause
Main article: Lyme disease microbiology
Borrelia bacteria, the causative agent of Lyme disease. Magnified 400 times.
Borrelia bacteria, the causative agent of Lyme disease. Magnified 400 times.
Ixodes scapularis, the primary vector of Lyme disease in eastern North America.
Ixodes scapularis, the primary vector of Lyme disease in eastern North America.
Lyme disease is caused by Gram-negative spirochetal bacteria from the genus Borrelia. At least 11 Borrelia species have been described, 3 of which are Lyme related.[23][24] The Borrelia species known to cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato, and have been found to have greater strain diversity than previously estimated.[25]
Three closely-related species of spirochetes are well-established as causing Lyme disease and are probably responsible for the large majority of cases: B. burgdorferi sensu stricto (predominant in North America, but also in Europe), B. afzelii, and B. garinii (both predominant in Eurasia).[23] Some studies have also proposed that B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease.[citation needed]
Transmission
Hard-bodied ticks of the genus Ixodes are the primary vectors of Lyme disease.[1] The majority of infections are caused by ticks in the nymph stage, since adult ticks are more easily detected and removed as a consequence of their relatively large size.[citation needed]
In Europe, the sheep tick, castor bean tick, or European castor bean tick (Ixodes ricinus) is the transmitter.[citation needed]
In North America, the black-legged tick or deer tick (Ixodes scapularis) has been identified as the key to the disease's spread on the east coast. Only about 20% of people infected with Lyme disease by the deer tick are aware of having had any tick bite,[26] making early detection difficult in the absence of a rash. Tick bites often go unnoticed because of the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite. The lone star tick (Amblyomma americanum), which is found throughout the Southeastern United States as far west as Texas, has been ruled out as a vector of the Lyme disease spirochete Borrelia burgdorferi,[citation needed] though it may be implicated with a clinical syndrome southern tick associated rash illness (STARI), which resembles the skin lesions of Lyme disease.[27]
On the West Coast, the primary vector is the western black-legged tick (Ixodes pacificus).[28] The tendency of this tick species to feed predominantly on host species that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West.[29][30]
While Lyme spirochetes have been found in insects other than ticks,[31] reports of actual infectious transmission appear to be rare.[32] Sexual transmission has been anecdotally reported; Lyme spirochetes have been found in semen[33] and breast milk,[34] however transmission of the spirochete by these routes is not known to occur.[35]
Congenital transmission of Lyme disease can occur from an infected mother to fetus through the placenta during pregnancy, however prompt antibiotic treatment appears to prevent fetal harm.[36]
Tick borne co-infections
Ticks that transmit B. burgorferi to humans can also carry and transmit several other parasites such as Babesia microti and Anaplasma phagocytophilum, which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively. Among early Lyme disease patients, depending on their location, 2-12% will also have HGA and 2-40% will have babesiosis.[37] Cat scratch fever is another common co-infection, although there is debate among experts on this topic on tick-to-human transmission.[citation needed]
Co-infections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the co-infections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control (CDC)'s emerging infections diseases department did a study in rural New Jersey of 100 ticks and found that 55% of the ticks were infected with at least one of the pathogens.[38]
Diagnosis
Lyme disease is diagnosed clinically based on symptoms, objective physical findings (such as erythema migrans, facial palsy, or arthritis), a history of possible exposure to infected ticks, as well as serological tests.
When making a diagnosis of Lyme disease, health care providers should consider other diseases that may cause similar illness. Not all patients with Lyme disease will develop the characteristic bulls-eye rash, and many may not recall a tick bite. Laboratory testing is not recommended for persons who do not have symptoms of Lyme disease.
Because of the difficulty in culturing Borrelia bacteria in the laboratory, diagnosis of Lyme disease is typically based on the clinical exam findings and a history of exposure to endemic Lyme areas.[1] The EM rash, which does not occur in all cases, is considered sufficient to establish a diagnosis of Lyme disease even when serologies are negative.[39][40] Serological testing can be used to support a clinically suspected case but is not diagnostic.[1] Clinicians who diagnose strictly based on the CDC Case Definition for Lyme may be in error, since the CDC explicitly states that this definition is intended for surveillance purposes only and is "not intended to be used in clinical diagnosis."[41][42]
Diagnosis of late-stage Lyme disease is often difficult because of the multi-faceted appearance which can mimic symptoms of many other diseases. For this reason, Lyme has often been called the new "great imitator".[43] Lyme disease may be misdiagnosed as multiple sclerosis, rheumatoid arthritis, fibromyalgia, chronic fatigue syndrome (CFS), lupus, or other autoimmune and neurodegenerative diseases.
Laboratory testing
Several forms of laboratory testing for Lyme disease are available, some of which have not been adequately validated. Most recommended tests are blood tests that measure antibodies made in response to the infection. These tests may be falsely negative in patients with early disease, but they are quite reliable for diagnosing later stages of disease.
The serological laboratory tests most widely available and employed are the Western blot and ELISA. A two-tiered protocol is recommended by the CDC: the more sensitive ELISA is performed first, if it is positive or equivocal, the more specific Western blot is run. The reliability of testing in diagnosis remains controversial,[1] however studies show the Western blot IgM has a specificity of 94–96% for patients with clinical symptoms of early Lyme disease.[44][45]
Erroneous test results have been widely reported in both early and late stages of the disease. These errors can be caused by several factors, including antibody cross-reactions from other infections including Epstein-Barr virus and cytomegalovirus,[46] as well as herpes simplex virus.[47]
Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA) of the Lyme disease spirochete. PCR tests are susceptible to false-positive results from poor laboratory technique.[48] Even when properly performed, PCR often shows false-negative results with blood and CSF specimens.[49] Hence PCR is not widely performed for diagnosis of Lyme disease. However PCR may have a role in diagnosis of Lyme arthritis because it is highly sensitive in detecting ospA DNA in synovial fluid.[50] With the exception of PCR, there is no currently practical means for detection of the presence of the organism, as serologic studies only test for antibodies of Borrelia. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading. The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years.[51]
Western blot, ELISA and PCR can be performed by either blood test via venipuncture or cerebrospinal fluid (CSF) via lumbar puncture. Though lumbar puncture is more definitive of diagnosis, antigen capture in the CSF is much more elusive; reportedly CSF yields positive results in only 10–30% of patients cultured. The diagnosis of neurologic infection by Borrelia should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.[52]
New techniques for clinical testing of Borrelia infection have been developed, such as LTT-MELISA,[53] which is capable of identifying the active form of Borrelia infection (Lyme disease). Others, such as focus floating microscopy, are under investigation.[54] New research indicates chemokine CXCL13 may also be a possible marker for neuroborreliosis.[55]
Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall-deficient forms of Borrelia burgdorferi, and lymphocyte transformation tests. In general, CDC does not recommend these tests.
Imaging
Single photon emission computed tomography (SPECT) imaging has been used to look for cerebral hypoperfusion indicative of Lyme encephalitis in the patient.[56] Although SPECT is not a diagnostic tool itself, it may be a useful method of determining brain function.
In Lyme disease patients, cerebral hypoperfusion of frontal subcortical and cortical structures has been reported.[57] In about 70% of chronic Lyme disease patients with cognitive symptoms, brain SPECT scans typically reveal a pattern of global hypoperfusion in a heterogeneous distribution through the white matter.[58] This pattern is not specific for Lyme disease, since it can also be seen in other central nervous system (CNS) syndromes such as HIV encephalopathy, viral encephalopathy, chronic cocaine use, and vasculitides. However, most of these syndromes can be ruled out easily through standard serologic testing and careful patient history taking.
The presence of global cerebral hypoperfusion deficits on SPECT in the presence of characteristic neuropsychiatric features should dramatically raise suspicion for Lyme encephalopathy among patients who inhabit or have traveled to endemic areas, regardless of patient recall of tick bites.[citation needed] Late disease can occur many years after initial infection. The average time from symptom onset to diagnosis in these patients is about 4 years. Because seronegative disease can occur, and because CSF testing is often normal, Lyme encephalopathy often becomes a diagnosis of exclusion: once all other possibilities are ruled out, Lyme encephalopathy becomes ruled in. Although the aberrant SPECT patterns are caused by cerebral vasculitis, a vasculitide, brain biopsy is not commonly performed for these cases as opposed to other types of cerebral vasculitis.
Abnormal magnetic resonance imaging (MRI) findings are often seen in both early and late Lyme disease.[citation needed] MRI scans of patients with neurologic Lyme disease may demonstrate punctuated white matter lesions on T2-weighted images, similar to those seen in demyelinating or inflammatory disorders such as multiple sclerosis, systemic lupus erythematosus (SLE), or cerebrovascular disease.[59] Cerebral atrophy and brainstem neoplasm has been indicated with Lyme infection as well.[60]
Diffuse white matter pathology can disrupt these ubiquitous gray matter connections and could account for deficits in attention, memory, visuospatial ability, complex cognition, and emotional status. White matter disease may have a greater potential for recovery than gray matter disease, perhaps because neuronal loss is less common. Spontaneous remission can occur in multiple sclerosis, and resolution of MRI white matter hyper-intensities, after antibiotic treatment, has been observed in Lyme disease.[61]
Prevention
Attached ticks should be removed promptly.[62] Protective clothing includes a hat and long-sleeved shirts and long pants that are tucked into socks or boots. Light-colored clothing makes the tick more easily visible before it attaches itself. People should use special care in handling and allowing outdoor pets inside homes because they can bring ticks into the house.
A more effective, community wide method of preventing Lyme disease is to reduce the numbers of primary hosts on which the deer tick depends such as rodents, other small mammals, and deer. Reduction of the deer population may over time help break the reproductive cycle of the deer ticks and their ability to flourish in suburban and rural areas.[63]
Management of host animals
Lyme and all other deer-tick-borne diseases can be prevented on a regional level by reducing the deer population that the ticks depend on for reproductive success. This has been demonstrated in the communities of Monhegan, Maine[64] and in Mumford Cove, Connecticut.[65] The black-legged or deer tick (Ixodes scapularis) depends on the white-tailed deer for successful reproduction.
For example, in the US, it is suggested that by reducing the deer population back to healthy levels of 8 to 10 per square mile (from the current levels of 60 or more deer per square mile in the areas of the country with the highest Lyme disease rates), the tick numbers can be brought down to levels too low to spread Lyme and other tick-borne diseases.[66]
Vaccination
A recombinant vaccine against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi, was developed by GlaxoSmithKline. In clinical trials involving more than 10,000 people, the vaccine, called LYMErix, was found to confer protective immunity to Borrelia in 76% of adults and 100% of children with only mild or moderate and transient adverse effects.[67] LYMErix was approved on the basis of these trials by the U.S. Food and Drug Administration (FDA) on December 21, 1998.
Following approval of the vaccine, its entry in clinical practice was slower than expected for a variety of reasons including its cost, which was often not reimbursed by insurance companies.[68] Subsequently, hundreds of vaccine recipients reported that they had developed autoimmune side effects. Supported by some patient advocacy groups, a number of class-action lawsuits were filed against GlaxoSmithKline alleging that the vaccine had caused these health problems. These claims were investigated by the FDA and the U.S. Centers for Disease Control (CDC), who found no connection between the vaccine and the autoimmune complaints.[69]
Despite the lack of evidence that the complaints were caused by the vaccine, sales plummeted and LYMErix was withdrawn from the U.S. market by GlaxoSmithKline in February 2002[70] in the setting of negative media coverage and fears of vaccine side effects.[71][69] The fate of LYMErix was described in the medical literature as a "cautionary tale";[71] an editorial in Nature cited the withdrawal of LYMErix as an instance in which "unfounded public fears place pressures on vaccine developers that go beyond reasonable safety considerations,"[72] while the original developer of the OspA vaccine at the Max Planck Institute told Nature: "This just shows how irrational the world can be... There was no scientific justification for the first OspA vaccine [LYMErix] being pulled."[69]
New vaccines are being researched using outer surface protein C (OspC) and glycolipoprotein as methods of immunization.[73][74]
Tick removal
Many urban legends exist about the proper and effective method to remove a tick, however it is generally agreed that the most effective method is to pull it straight out with tweezers.[75] Data have demonstrated that prompt removal of an infected tick, within approximately 36 hours, reduces the risk of transmission to nearly zero; however the small size of the tick, especially in the nymph stage, may make detection difficult.[62]
Treatment
Antibiotics are the primary treatment for Lyme disease; the most appropriate antibiotic treatment depends upon the patient and the stage of the disease.[1] The antibiotics of choice are doxycycline (in adults), amoxicillin (in children), and ceftriaxone. Alternative choices are cefuroxime and cefotaxime.[1] Macrolide antibiotics have limited efficacy when used alone. Physicians who treat chronic Lyme disease have noted that combining a macrolide antibiotic such as clarithromycin (biaxin) with hydroxychloroquine (plaquenil) is especially effective in treatment of chronic Lyme disease.[76] It is thought that the hydroxychloroquine raises the pH of intracellular acidic vacuoles in which B. burgdorferi may reside; raising the pH is thought to activate the macrolide antibiotic, allowing it to inhibit protein synthesis by the spirochete.[76]
Results of a recent double blind, randomized, placebo-controlled multicenter clinical study, done in Finland, indicated that oral adjunct antibiotics were not justified in the treatment of patients with disseminated Lyme borreliosis who initially received intravenous antibiotics for three weeks. The researchers noted the clinical outcome of said patients should not be evaluated at the completion of intravenous antibiotic treatment but rather 6–12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies did not seem to provide any useful information for further care of the patient.[77]
In later stages, the bacteria disseminate throughout the body and may cross the blood-brain barrier, making the infection more difficult to treat. Late diagnosed Lyme is treated with oral or IV antibiotics, frequently ceftriaxone, 2 grams per day, for a minimum of four weeks. Minocycline is also indicated for neuroborreliosis for its ability to cross the blood-brain barrier.[78]
"Post-Lyme syndrome" and "chronic Lyme disease"
Further information: Lyme disease controversy
Some Lyme disease patients who have completed a course of antibiotic treatment continue to have symptoms such as severe fatigue, sleep disturbance, and cognitive difficulties. Some groups have attributed these symptoms to persistent infection with Borrelia and have advocated long-term antibiotic treatment in such cases.[79] However, three randomized controlled trials showed no benefit from long-term antibiotic treatment in such patients.[4][5][6] A fourth randomized trial, published in 2008 by a group which advocates long-term antibiotic treatment, reported a short-term and statistically insignificant improvement in cognition with the antibiotic ceftriaxone, but this improvement was not maintained in the long-term.[80] These trials identified significant side effects and risks of prolonged antibiotic therapy, and at least one death has been reported from complications of a 27-month course of intravenous antibiotics for an unsubstantiated diagnosis of "chronic Lyme disease".[81]
Thus, most medical authorities, including the Infectious Diseases Society of America and the American Academy of Neurology, have found that there is no convincing evidence that Borrelia is implicated in the various syndromes of "chronic Lyme disease", and recommend against long-term antibiotic treatment as ineffective and possibly harmful.[82][83][7]
Antibiotic-resistant therapies
Antibiotic treatment is the central pillar in the management of Lyme disease. In the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment.[84][85] Lyme arthritis which is antibiotic resistant may be treated with hydroxychloroquine or methotrexate.[86] Experimental data are consensual on the deleterious consequences of systemic corticosteroid therapy. Corticosteroids are not indicated in Lyme disease.[87]
Antibiotic refractory patients with neuropathic pain responded well to gabapentin monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study.[88] The immunomodulating, neuroprotective and anti-inflammatory potential of minocycline may be helpful in late/chronic Lyme disease with neurological or other inflammatory manifestations. Minocycline is used in other neurodegenerative and inflammatory disorders such as multiple sclerosis, Parkinson's disease, Huntington's disease, rheumatoid arthritis (RA) and ALS.[89]
Alternative therapies
A number of other alternative therapies have been suggested, though clinical trials have not been conducted. For example, the use of hyperbaric oxygen therapy (which is used conventionally to treat a number of other conditions), as an adjunct to antibiotics for Lyme has been discussed.[90] Though there are no published data from clinical trials to support its use, preliminary results using a mouse model suggest its effectiveness against B. burgdorferi both in vitro and in vivo.[91] Anecdotal clinical research has shown potential for the antifungal azole medications such as diflucan in the treatment of Lyme, but has yet to be repeated in a controlled study or postulated a developed hypothetical model for its use.[92]
Alternative medicine approaches include bee venom because it contains the peptide melittin, which has been shown to exert inhibitory effects on Lyme bacteria in vitro;[93] no clinical trials of this treatment have been carried out, however.
Prognosis
For early cases, prompt treatment is usually curative.[94] However, the severity and treatment of Lyme disease may be complicated due to late diagnosis, failure of antibiotic treatment, and simultaneous infection with other tick-borne diseases (co-infections) including ehrlichiosis, babesiosis, and bartonella, and immune suppression in the patient.
A meta-analysis published in 2005 found that some patients with Lyme disease have fatigue, joint or muscle pain, and neurocognitive symptoms persisting for years despite antibiotic treatment.[95] Patients with late stage Lyme disease have been shown to experience a level of physical disability equivalent to that seen in congestive heart failure.[96] In rare cases, Lyme disease can be fatal.[97]
Ecology
Urbanization and other anthropogenic factors can be implicated in the spread of Lyme disease to humans. In many areas, expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increasing border contact between humans and tick-dense areas. Human expansion has also resulted in a gradual reduction of the predators that normally hunt deer as well as mice, chipmunks and other small rodents – the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector, the likelihood of transmission to Lyme residents has greatly increased.[98][99] Researchers are also investigating possible links between global warming and the spread of vector-borne diseases including Lyme disease.[100]
The deer tick (Ixodes scapularis, the primary vector in the northeastern U.S.) has a two-year life cycle, first progressing from larva to nymph, and then from nymph to adult. The tick feeds only once at each stage. In the fall, large acorn forests attract deer as well as mice, chipmunks and other small rodents infected with B. burgdorferi. During the following spring, the ticks lay their eggs. The rodent population then "booms". Tick eggs hatch into larvae, which feed on the rodents; thus the larvae acquire infection from the rodents. At this stage, tick infestation may be controlled using acaricides (miticides).
Adult ticks may also transmit disease to humans. After feeding, female adult ticks lay their eggs on the ground, and the cycle is complete. On the West Coast of the United States, Lyme disease is spread by the western black-legged tick (Ixodes pacificus), which has a different life cycle.
The risk of acquiring Lyme disease does not depend on the existence of a local deer population, as is commonly assumed. New research suggests that eliminating deer from smaller areas (less than 2.5 ha or 6 acres) may in fact lead to an increase in tick density and the rise of "tick-borne disease hotspots".[101]
Epidemiology
Lyme disease is the most common tick-borne disease in North America and Europe and one of the fastest-growing infectious diseases in the United States. Of cases reported to the United States CDC, the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.[102]
Although Lyme disease has been reported in 49 of 50 states in the U.S, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central).[103] New 2008 CDC Lyme case definition guidelines are used to determine confirmed CDC surveillance cases.[104] Effective January 2008, the CDC gives equal weight to laboratory evidence from 1) a positive culture for B. burgdorferi; 2) two-tier testing (ELISA screening and Western Blot confirming); or 3) single-tier IgG (old infection) Western Blot. Previously, the CDC only included laboratory evidence based on (1) and (2) in their surveillance case definition. The case definition now includes the use of Western Blot without prior ELISA screen.
The number of reported cases of the disease have been increasing, as are endemic regions in North America. For example, it had previously been thought that B. burgdorferi sensu lato was hindered in its ability to be maintained in an enzootic cycle in California because it was assumed the large lizard population would dilute the prevalence of B. burgdorferi in local tick populations, but this has since been brought into question as some evidence has suggested that lizards can become infected.[105] Except for one study in Europe,[106] much of the data implicating lizards is based on DNA detection of the spirochete and has not demonstrated that lizards are able to infect naive ticks feeding upon them.[107][108][109][110] As some experiments suggest lizards are refractory to infection with Borrelia, it appears likely their involvement in the enzootic cycle is more complex and species-specific.[30]
While B. burgdorferi is most associated with ticks hosted by white-tailed deer and white-footed mice, Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, Borrelia garinii and Borrelia valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for B. burgdorferi sensu stricto. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association.
In Europe, cases of B. burgdorferi sensu lato infected ticks are found predominantly in Norway, Netherlands, Germany, France, Italy, Slovenia and Poland, but have been isolated in almost every country on the continent.[111]
B. burgdorferi sensu lato infested ticks are being found more frequently in Japan, as well as in Northwest China and far eastern Russia.[112][113] Borrelia has been isolated in Mongolia as well.[114]
In South America tick-borne disease recognition and occurrence is rising. Ticks carrying B. burgdorferi sensu lato, as well as canine and human tick-borne disease, have been reported widely in Brazil, but the subspecies of Borrelia has not yet been defined.[115] The first reported case of Lyme disease in Brazil was made in 1993 in Sao Paulo.[116] B. burgdorferi sensu stricto antigens in patients have been identified in Colombia and Bolivia.
In Northern Africa B. burgdorferi sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia.[117][118][119]
Lyme disease in sub-Saharan is presently unknown, but evidence indicates that Lyme disease may occur in humans in this region. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa.[120] In East Africa, two cases of Lyme disease have been reported in Kenya.[121]
In Australia there is no definitive evidence for the existence of B. burgdorferi or for any other tick-borne spirochete that may be responsible for a local syndrome being reported as Lyme disease.[122] Cases of neuroborreliosis have been documented in Australia but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.
Northern hemisphere temperate regions are most endemic for Lyme disease.[123][124]
Controversy and politics
Main article: Lyme disease controversy
While there is general agreement on the optimal treatment of early Lyme disease, considerable controversy has attached to the existence, prevalence, diagnostic criteria, and treatment of "chronic" Lyme disease. Most medical authorities—including the Infectious Diseases Society of America (IDSA), the American Academy of Neurology, and the Centers for Disease Control—do not recommend long-term antibiotic treatment for "chronic" Lyme disease, based on evidence that such treatment is ineffective and potentially harmful.
Groups of patients, patient advocates, and physicians who support the concept of chronic Lyme disease have organized to lobby for insurance coverage of long-term antibiotic therapy, which most insurers deny given medical opinion that it is ineffective and potentially harmful.[125] As part of this controversy, Connecticut Attorney General Richard Blumenthal opened an antitrust investigation against the IDSA, accusing the IDSA panel of undisclosed conflicts of interest and of unduly dismissing alternative therapies. This investigation was closed on May 1, 2008 without formal charges; the IDSA agreed to a review of its guidelines by a panel of independent scientists and physicians.[126] Blumenthal's corresponding press release announcing the agreement focused on alleged wrongdoing by the IDSA,[127] while the IDSA's press release focused on the fact that the medical validity of the IDSA guidelines was not challenged.[128] Paul G. Auwaerter, director of infectious disease at Johns Hopkins School of Medicine, cited this political controversy as an example of the "poisonous atmosphere" surrounding Lyme disease research which has led younger researchers to avoid the field.[126]
In 2001, the New York Times Magazine reported that Allen Steere, chief of immunology and rheumatology at New England Medical Center and a leading expert on Lyme disease, had been harassed, stalked, and threatened by patients and patient advocacy groups angry at his refusal to substantiate their diagnoses of "chronic" Lyme disease and endorse long-term antibiotic therapy.[129] Because of death threats, security guards were assigned to Steere.[69]
A significant amount of inaccurate information on Lyme disease exists on the Internet. A 2004 study found that 9 of 19 websites surveyed contained major inaccuracies. Sites found to be good sources of accurate information in this study included those of the American College of Physicians, the Centers for Disease Control, the Food and Drug Administration, and Johns Hopkins University (www.hopkins-arthritis.org).[130]
Pathophysiology
Borrelia burgdorferi has the ability to disseminate to numerous organs during the course of disease. The spirochete has been found in many tissues, including the skin, heart, joint, peripheral nervous system, and central nervous system.[131][132] Many of the signs and symptoms of Lyme disease are a consequence of the inflammatory response to the presence of the spirochete in those tissues. [133]
B. burgdorferi is injected into the skin by the bite of an infected Ixodes tick. Tick saliva, which accompanies the spirchete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite. [134] This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the dermis. The host inflammatory response to the bacteria in the skin is associated with the appearance of the characteristic EM lesion.[131] However neutrophils, which are necessary to eliminate the spirochetes from the skin, fail to appear in the developing EM lesion thereby permitting the bacteria to survive and eventually spread throughout the body.[135]
Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of clinical manifestations of disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete. [136] The bacteria may persist at these sites for months or even years despite active production of anti-B. burgdorferi antibodies by the immune response. The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by the immune response, antigenic variation of the VlsE surface protein, inactivating key immune components such as complement, and hiding in the extracellular matrix, which may interfere with the function of immune factors. [137][138]
In the brain B. burgdorferi may induce astrocytes to undergo astrogliosis (proliferation followed by apoptosis), which may contribute to neurodysfunction.[139] The spirochetes may also induce host cells to secrete products toxic to nerve cells, including quinolinic acid and the cytokines IL-6 and TNF-alpha, which can produce fatigue and malaise.[140][141][142] Both microglia and astrocytes secrete IL-6 and TNF-alpha in the presence of the spirochete.[139][143] IL-6 is also significantly indicated in cognitive impairment.[144]
A developing hypothesis is that the chronic secretion of stress hormones as a result of Borrelia infection may reduce the effect of neurotransmitters, or other receptors in the brain by cell-mediated pro-inflammatory pathways, thereby leading to the dysregulation of neurohormones, specifically glucocorticoids and catecholamines, the major stress hormones.[145][146] This process is mediated via the hypothalamic-pituitary-adrenal axis. Additionally tryptophan, a precursor to serotonin appears to be reduced within the central nervous system (CNS) in a number of infectious diseases that affect the brain, including Lyme.[147] Researchers are investigating if this neurohormone secretion is the cause of neuropsychiatric disorders developing in some patients with borreliosis.[148]
Antidepressants acting on serotonin, norepinephrine and dopamine receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psycho-neuroimmunological process.[149] Antidepressants have also been shown to suppress Th1 upregulation.[150]
Immunological studies
Research has found that chronic Lyme patients have higher amounts of Borrelia-specific forkhead box P3 (FoxP3) than healthy controls, indicating that regulatory T cells might also play a role, by immunosuppression, in the development of chronic Lyme disease. FoxP3 are a specific marker of regulatory T cells.[151] The signaling pathway P38 mitogen-activated protein kinases (p38 MAP kinase) has also been identified as promoting expression of pro-inflammatory cytokines from Borrelia.[152]
These immunological studies suggest that cell-mediated immune disruption in the Lyme patient amplifies the inflammatory process, often rendering it chronic and self-perpetuating, regardless of whether the Borrelia bacterium is still present in the host. This would be a form of pathogen-induced autoimmune disease.[153] It is therefore possible that chronic symptoms could come from an autoimmune reaction, even after the spirochetes have been eliminated from the body. This hypothesis may explain chronic arthritis that persists after antibiotic therapy, but the wider application of this hypothesis is controversial.[154][155]
History
The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in Wrocław, Poland (then known as Breslau, Germany) where physician Alfred Buchwald described a man who had suffered for 16 years with a degenerative skin disorder now known as acrodermatitis chronica atrophicans. At a 1909 research conference, Swedish dermatologist Arvid Afzelius presented a study about an expanding, ring-like lesion he had observed in an older woman following the bite of a sheep tick. He named the lesion erythema migrans.[156] The skin condition now known as borrelial lymphocytoma was first described in 1911.[157]
Neurological problems following tick bites were recognized starting in the 1920s. French physicians Garin and Bujadoux described a farmer with a painful sensory radiculitis accompanied by mild meningitis following a tick bite. A large ring-shaped rash was also noted, although the doctors did not relate it to the meningoradiculitis. In 1930, the Swedish dermatologist Sven Hellerstrom was the first to propose that EM and neurological symptoms following a tick bite were related.[158] In the 1940s, German neurologist Alfred Bannwarth described several cases of chronic lymphocytic meningitis and polyradiculoneuritis, some of which were accompanied by erythematous skin lesions.
Carl Lennhoff, who worked at the Karolinska Institute in Sweden, believed that many skin conditions were caused by spirochetes. In 1948, he used a special stain to microscopically observe what he believed were spirochetes in various types of skin lesions, including EM.[159] Although his conclusions were later shown to be erroneous, interest in the study of spirochetes was sparked. In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin.[160] In the 1950s, the relationship among tick bite, lymphocytoma, EM and Bannwarth's syndrome was recognized throughout Europe leading to the widespread use of penicillin for treatment in Europe.[161][162]
In 1970 a dermatologist in Wisconsin named Rudolph Scrimenti recognized an EM lesion in a patient after recalling a paper by Hellerstrom that had been reprinted in an American science journal in 1950. This was the first documented case of EM in the United States. Based on the European literature, he treated the patient with penicillin.[163]
The full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1975, including the towns Lyme and Old Lyme, which gave the disease its popular name.[164] This was investigated by physicians David Snydman and Allen Steere of the Epidemic Intelligence Service, and by others from Yale University. The recognition that the patients in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe.[165]
Before 1976, elements of B. burgdorferi sensu lato infection were called or known as tickborne meningopolyneuritis, Garin-Bujadoux syndrome, Bannworth syndrome, Afzelius syndrome, Montauk Knee or sheep tick fever. Since 1976 the disease is most often referred to as Lyme disease,[166][167] Lyme borreliosis or simply borreliosis.
In 1980 Steere, et al, began to test antibiotic regimens in adult patients with Lyme disease.[168] In 1982 a novel spirochete was cultured from the mid-gut of Ixodes ticks in Shelter Island, New York, and subsequently from patients with Lyme disease. The infecting agent was then identified by Jorge Benach at the State University of New York at Stony Brook, and soon after isolated by Willy Burgdorfer, a researcher at the National Institutes of Health, who specialized in the study of arthropod-borne bacteria such as Borrelia and Rickettsia. The spirochete was named Borrelia burgdorferi in his honor. Burgdorfer was the partner in the successful effort to culture the spirochete, along with Alan Barbour.
After identification B. burgdorferi as the causative agent of Lyme disease, antibiotics were selected for testing, guided by in vitro antibiotic sensitivities, including tetracycline antibiotics, amoxicillin, cefuroxime axetil, intravenous and intramuscular penicillin and intravenous ceftriaxone.[169][170] The mechanism of tick transmission was also the subject of much discussion. B. burgdorferi spirochetes were identified in tick saliva in 1987, confirming the hypothesis that transmission occurred via tick salivary glands
Showing posts with label diseases coughing whooping cough disease information analysis advice community personals. Show all posts
Showing posts with label diseases coughing whooping cough disease information analysis advice community personals. Show all posts
Saturday, July 12, 2008
Myopia reference
Myopia (from Greek: μυωπία myopia "near-sightedness"[1]), also called near- or short-sightedness, is a refractive defect of the eye in which collimated light produces image focus in front of the retina when accommodation is relaxed.
Those with myopia see nearby objects clearly but distant objects appear blurred. With myopia, the eyeball is too long, or the cornea is too steep, so images are focused in the vitreous inside the eye rather than on the retina at the back of the eye. The opposite defect of myopia is hyperopia or "farsightedness" or "long-sightedness" — this is where the cornea is too flat or the eye is too short.
Mainstream ophthalmologists and optometrists most commonly correct myopia through the use of corrective lenses, such as glasses or contact lenses. It may also be corrected by refractive surgery, such as LASIK. The corrective lenses have a negative optical power (i.e. are concave) which compensates for the excessive positive diopters of the myopic eye. In some cases, pinhole glasses are used by patients with low-level myopia. These work by reducing the blur circle formed on the retina.
Etiology
Borish and Duke-Elder classified myopia by cause:[3][4]
* Axial myopia is attributed to an increase in the eye's axial length.[5]
* Refractive myopia is attributed to the condition of the refractive elements of the eye.[5] Borish further subclassified refractive myopia:[3]
* Curvature myopia is attributed to excessive, or increased, curvature of one or more of the refractive surfaces of the eye, especially the cornea.[5] In those with Cohen syndrome, myopia appears to result from high corneal and lenticular power.
* Index myopia is attributed to variation in the index of refraction of one or more of the ocular media.
Clinical entity
Various forms of myopia have been described by their clinical appearance:[4][7]
* Simple myopia is more common than other types of myopia and is characterized by an eye that is too long for its optical power (which is determined by the cornea and crystalline lens) or optically too powerful for its axial length.[8] Both genetic and environmental factors, particularly significant amounts of near work, are thought to contribute to the development of simple myopia.[8]
* Degenerative myopia, also known as malignant, pathological, or progressive myopia, is characterized by marked fundus changes, such as posterior staphyloma, and associated with a high refractive error and subnormal visual acuity after correction.[5] This form of myopia gets progressively worse over time. Degenerative myopia has been reported as one of the main causes of visual impairment.[9] Myopia with degenerative changes has been described as being very common in certain races and cultures, such as Chinese, Japanese, Korean, Arab, White, and Jewish people.[10]
* Nocturnal myopia, also known as night myopia or twilight myopia, is a condition in which the eye has a greater difficulty seeing in low illumination areas, even though its daytime vision is normal. Essentially, the eye's far point of an individual's focus varies with the level of light. Night myopia is believed to be caused by pupils dilating to let more light in, which adds aberrations resulting in becoming more nearsighted. A stronger prescription for myopic night drivers is often needed. Younger people are more likely to be affected by night myopia than the elderly.[11]
* Pseudomyopia is the blurring of distance vision brought about by spasm of the ciliary muscle.[12]
* Induced myopia, also known as acquired myopia, results from exposure to various pharmaceuticals, increases in glucose levels, nuclear sclerosis, or other anomalous conditions.[8] The encircling bands used in the repair of retinal detachments may induce myopia by increasing the axial length of the eye.[13]
* Index myopia is attributed to variation in the index of refraction of one or more of the ocular media.[5] Cataracts may lead to index myopia.[14]
* Form deprivation myopia is a type of myopia that occurs when the eye is deprived of clear form vision.[15] Myopia is often induced this way in various animal models to study the pathogenesis and mechanism of myopia development.
Degree
Myopia, which is measured in diopters by the strength or optical power of a corrective lens that focuses distant images on the retina, has also been classified by degree or severity:[2]
* Low myopia usually describes myopia of −3.00 diopters or less.[5]
* Medium myopia usually describes myopia between −3.00 and −6.00 diopters.[5] Those with moderate amounts of myopia are more likely to have pigment dispersion syndrome or pigmentary glaucoma.[16]
* High myopia usually describes myopia of −6.00 or more.[5] People with high myopia are more likely to have retinal detachments[17] and primary open angle glaucoma.[18] They are also more likely to experience floaters, shadow-like shapes which appear singly or in clusters in the field of vision.[citation needed] Roughly 30% of myopes have high myopia.
Age of onset
Myopia is sometimes classified by the age of onset:
* Congenital myopia, also known as infantile myopia, is present at birth and persists through infancy.
* Youth onset myopia occurs prior to age 20.
* School myopia appears during childhood, particularly the school-age years. This form of myopia is attributed to the use of the eyes for close work during the school years.
* Adult onset myopia
* Early adult onset myopia occurs between ages 20 and 40.[8]
* Late adult onset myopia occurs after age 40.
Epidemiology
The global prevalence of refractive errors has been estimated from 800 million to 2.3 billion.[20] The incidence of myopia within sampled population often varies with age, country, sex, race, ethnicity, occupation, environment, and other factors.[10][21] Variability in testing and data collection methods makes comparisons of prevalence and progression difficult.[22]
In some areas, such as Japan, Singapore and Taiwan, up to 44% of the adult population is myopic.[citation needed]
A recent study involving first-year undergraduate students in the United Kingdom found that 50% of British whites and 53.4% of British Asians were myopic.[23]
In Australia, the overall prevalence of myopia (worse than −0.50 diopters) has been estimated to be 77%.[24] In one recent study, less than 1 in 10 (8.4%) Australian children between the ages of 4 and 12 were found to have myopia greater than −0.50 diopters.[25] A recent review found that 16.4% of Australians aged 40 or over have at least −1.00 diopters of myopia and 2.5% have at least −5.00 diopters.[26]
In Brazil, a 2005 study estimated that 6.4% of Brazilians between the ages of 12 and 59 had −1.00 diopter or myopia or more, compared with 2.7% of the indigenous people in northwestern Brazil.[27] Another found nearly 1 in 8 (13.3%) of the students in one city were myopic.[28]
In Greece, the prevalence of myopia among 15 to 18 year old students was found to be 36.8%.
In India, the prevalence of myopia in the general population has been reported to be only 6.9%.[30][29]
A recent review found that 26.6% of Western Europeans aged 40 or over have at least −1.00 diopters of myopia and 4.6% have at least −5.00 diopters.[31]
In the United States, the prevalence of myopia has been estimated at 20%.[10] Nearly 1 in 10 (9.2%) American children between the ages of 5 and 17 have myopia.[32] Approximately 25% of Americans between the ages of 12 and 54 have the condition.[33] A recent review found that 25.4% of Americans aged 40 or over have at least −1.00 diopters of myopia and 4.5% have at least −5.00 diopters.[34]
A study of Jordanian adults aged 17 to 40 found that over half (53.7%) were myopic.[35]
Ethnicity and race
The prevalence of myopia has been reported as high as 70-90% in some Asian countries. 30-40% in Europe and the United States, and 10-20% in Africa.[21]
Myopia is less common in black and African people.[10] In Americans between the ages of 12 and 54, myopia has been found to affect blacks less than whites[33]. Asians had the highest prevalence (78.5%), followed by Hispanics (13.2%). Whites had the lowest prevalence of myopia (4.4%), which was not significantly different from African Americans (6.6%). For hyperopia, whites had the highest prevalence (19.3%), followed by Hispanics (12.7%). Asians had the lowest prevalence of hyperopia (6.3%) and were not significantly different from African Americans (6.4%). For astigmatism, Asians and Hispanics had the highest prevalences (33.6% and 36.9%, respectively) and did not differ from each other (P = .17). African Americans had the lowest prevalence of astigmatism (20.0%), followed by whites (26.4%).[36]
Education, intelligence, and IQ
A number of studies have shown that the prevalence of myopia increases with level of education and many studies have shown a relationship between myopia and IQ. However, care must be taken in interpreting these results as correlation does not imply causation.
According to Arthur Jensen, myopes average 7-8 IQ points higher than non-myopes. The relationship also holds within families, and siblings with a higher degree of refraction error average higher IQs than siblings with less refraction error. Jensen believes that this indicates myopia and IQ are pleiotropically related as they are caused or influenced by the same genes. No specific mechanism that could cause a relationship between myopia and IQ has yet been identified. Another possible explanation is that high levels of reading is a common cause for both intelligence and myopia, as it supposed that large amounts of close work is a causal factor of myopia[8].
Etiology and pathogenesis
Because in the most common, "simple" myopia, the eye length is too long, any etiologic explanation must account for such axial elongation. To date, no single theory has been able to satisfactorily explain this elongation.
In the early 1900s, controversial ophthalmologist William Bates asserted that myopia, as with all refractive errors, resulted from a particular type of "eyestrain" that was itself a result of "mental strain".[37] He stated that the shape of the eyeball responded instantaneously to the action of the extraocular muscles upon it[38] and that myopia was produced due to contraction of the inferior oblique and superior oblique muscles which lengthened the eye.[39] According to Bates, myopia was associated not with near work but with a "strain" to see distant objects; he believed that corrective lenses aggravated this strain and made myopia become progressively worse over time.[40] Encouraging his patients to discard their glasses, he advocated various techniques, now collectively known as the Bates Method, that he believed would enhance visual acuity by relaxing the eye. Although his theories were rejected by mainstream ophthalmologists of his time, and remain discredited in the profession today,[41][42] many people (including English author Aldous Huxley, who was taught by Margaret Darst Corbett, a disciple of Bates) claim to have reduced or eliminated their myopia by using his methods. However, no scientific studies have demonstrated its efficacy and the evidence supporting it remains largely anecdotal.
In the mid-1900s, mainstream ophthalmologists and optometrists believed myopia to be primarily hereditary; the influence of near work in its development seemed "incidental" and the increased prevalence of the condition with increasing age was viewed as a "statistical curiosity".[3][4][43]
Among mainstream researchers and eye care professionals, myopia is now thought to be a combination of genetic and environmental factors.[8][19]
There are currently two basic mechanisms believed to cause myopia: form deprivation (also known as pattern deprivation[44]) and optical defocus.[45] Form deprivation occurs when the image quality on the retina is reduced; optical defocus occurs when light focuses in front of or behind the retina. Numerous experiments with animals have shown that myopia can be artificially generated by inducing either of these conditions. In animal models wearing negative spectacle lenses, axial myopia has been shown to occur as the eye elongates to compensate for optical defocus.[45] The exact mechanism of this image-controlled elongation of the eye is still unknown.[citation needed] It has been suggested that accommodative lag leads to blur (i.e. optical defocus) which in turn stimulates axial elongation and myopia.[46]
Theories
* Combination of genetic and environmental factors — In China, myopia is more common in those with higher education background[47] and some studies suggest that near work may exacerbate a genetic predisposition to develop myopia.[48] Other studies have shown that near work (reading, computer games) may not be associated with myopic progression, however.[49] A "genetic susceptibility" to environmental factors has been postulated as one explanation for the varying degrees of myopia among individuals or populations,[50] but there exists some difference of opinion as to whether it exists.[19][51] High heritability simply means that most of the variation in a particular population at a particular time is due to genetic differences. If the environment changes — as, for example, it has by the introduction of televisions and computers — the incidence of myopia can change as a result, even though heritability remains high. From a slightly different point of view it could be concluded that — determined by heritage — some people are at a higher risk to develop myopia when exposed to modern environmental conditions with a lot of extensive near work like reading. In other words, it is often not the myopia itself which is inherited, but the reaction to specific environmental conditions — and this reaction can be the onset and the progression of myopia.
* Genetic factors — The wide variability of the prevalence of myopia in different ethnic groups has been reported as additional evidence supporting the role of genetics in the development of myopia.[52] Measures of the heritability of myopia have yielded figures as high as 89%, and recent research has identified genes that may be responsible: defective versions of the PAX6 gene seem to be associated with myopia in twin studies [1]. Under this theory, the eye is slightly elongated front to back as a result of faults during development, causing images to be focused in front of the retina rather than directly on it. It is usually discovered during the pre-teen years between eight and twelve years of age. It most often worsens gradually as the eye grows during adolescence and then levels off as a person reaches adulthood. Genetic factors can work in various biochemical ways to cause myopia, a weak or degraded connective tissue is a very essential one. Genetic factors include an inherited, increased susceptibility for environmental influences like excessive near work, and the fact that some people do not develop myopia in spite of very adverse conditions is a clear indication that heredity is involved somehow in any case.
* Environmental factors — It has been suggested that a genetic susceptibility to myopia does not exist.[19] A high heritability of myopia (as for any other condition) does not mean that environmental factors and lifestyle have no effect on the development of the condition. Some recommend a variety of eye exercises to strengthen the ciliary muscle. Other theories suggest that the eyes become strained by the constant extra work involved in "nearwork" and get stuck in the near position, and eye exercises can help loosen the muscles up thereby freeing it for far vision. These primarily mechanical models appear to be in contrast to research results, which show that the myopic elongation of the eye can be caused by the image quality, with biochemical processes as the actuator. Common to both views is, however, that extensive near work and corresponding accommodation can be essential for the onset and the progression of myopia.
One Austrian study confirmed that the axial length of the eye does mildly increase while reading, but attributed this elongation due to contraction of the ciliary muscle during accommodation (the process by which the eye increases optical power to maintain a clear image focus), not "squeezing" of the extraocular muscles.[53]
Near work and nightlight exposure in childhood have been hypothesized as environmental risk factors for myopia.[54] Although one initial study indicated a strong association between myopia and nightlight exposure,[55] recent research has found none.[54][56][57][58]
* Near work. Near work has been implicated as a contributing factor to myopia in some studies, but refuted in others.[59] One recent study suggested that students exposed to extensive "near work" may be at a higher risk of developing myopia, whereas extended breaks from near work during summer or winter vacations may retard myopic progression [2]. Near work in certain cultures (e.g. Vanuatu) does not result in greater myopia[3][4][5][6]. It has been hypothesized that this outcome may be a results of genetics or environmental factors such as diet or over-illumination, changes in which seem to occur in Asian, Vanuatu and Inuit cultures acclamating to intensive early studies[7].
* Diet and nutrition - One 2002 article suggested that myopia may be caused by over-consumption of bread in childhood, or in general by diets too rich in carbohydrates, which can lead to chronic hyperinsulinemia. Various other components of the diet, however, were made responsible for contributing to myopia as well, as summarized in a documentation.
* Stress has been postulated as a factor in the development of myopia.[60]
Relevant research
* A Turkish study found that accommodative convergence, rather than accommodation, may be a factor in the onset and progression of myopia in adults.[61]
* A recent Polish study revealed that "with-the-rule astigmatism" may lead to the creation of myopia.[62]
Presbyopia and the 'payoff' for the nearsighted
Many people with myopia are able to read comfortably without eyeglasses even in advanced age. Myopes considering refractive surgery are advised that this may be a disadvantage after the age of 40 when the eyes become presbyopic and lose their ability to accommodate or change focus.
Diagnosis
A diagnosis of myopia is typically confirmed during an eye examination by an ophthalmologist or an optometrist. Frequently an autorefractor or retinoscope is used to give an initial objective assessment of the refractive status of each eye, then a phoropter is used to subjectively refine the patient's eyeglass prescription.
Treatment, management, and prevention
Glasses are commonly used to address short-sightedness.
Eyeglasses, contact lenses, and refractive surgery are the primary options to treat the visual symptoms of those with myopia. Orthokeratology is the practice of using special rigid contact lenses to flatten the cornea to reduce myopia.
Eye-exercises and biofeedback
Practitioners and advocates of alternative therapies often recommend eye exercises and relaxation techniques such as the Bates method. However, the efficacy of these practices is disputed by scientists and eye care practitioners.[41] A 2005 review of scientific papers on the subject concluded that there was "no clear scientific evidence" that eye exercises were effective in treating myopia.[42]
In the eighties and nineties, there was a flurry of interest in biofeedback as a possible treatment for myopia. A 1997 review of this biofeedback research concluded that "controlled studies to validate such methods ... have been rare and contradictory."[63] It was found in one study that myopes could improve their visual acuity with biofeedback training, but that this improvement was "instrument-specific" and did not generalise to other measures or situations.[64] In another study an "improvement" in visual acuity was found but the authors concluded that this could be a result of subjects learning the task.[65] Finally, in an evaluation of a training system designed to improve acuity, "no significant difference was found between the control and experimental subjects".[66]
Prevention
There is no universally accepted method of preventing myopia.[8] Some clinicians and researchers recommend plus power (convex) lenses in the form of single vision reading lenses or bifocals.[8][67] A recent Malaysian study reported in New Scientist[68] suggested that undercorrection of myopia caused more rapid progression of myopia,[69] However, the reliability of this data has been called into question.[70] Many myopia treatment studies suffer from any of a number of design drawbacks: small numbers, lack of adequate control group, failure to mask examiners from knowledge of treatments used, etc.
Pirenzepine eyedrops had a limited effect on retarding myopic progression in a recent, placebo-control, double-blinded prospective controlled study.[71]
Myopia control
Various methods have been employed in an attempt to decrease the progression of myopia.[45] Altering the use of eyeglasses between full-time, part-time, and not at all does not appear to alter myopia progression.[72][73] Bifocal and progressive lenses have not shown significant differences in altering the progression of myopia.[45]
Myopia as metaphor
The terms myopia and myopic (or the common terms short sightedness or short sighted) have also been used metaphorically to refer to cognitive thinking and decision making that is narrow sighted or lacking in concern for wider interests or longer-term consequences.
Those with myopia see nearby objects clearly but distant objects appear blurred. With myopia, the eyeball is too long, or the cornea is too steep, so images are focused in the vitreous inside the eye rather than on the retina at the back of the eye. The opposite defect of myopia is hyperopia or "farsightedness" or "long-sightedness" — this is where the cornea is too flat or the eye is too short.
Mainstream ophthalmologists and optometrists most commonly correct myopia through the use of corrective lenses, such as glasses or contact lenses. It may also be corrected by refractive surgery, such as LASIK. The corrective lenses have a negative optical power (i.e. are concave) which compensates for the excessive positive diopters of the myopic eye. In some cases, pinhole glasses are used by patients with low-level myopia. These work by reducing the blur circle formed on the retina.
Etiology
Borish and Duke-Elder classified myopia by cause:[3][4]
* Axial myopia is attributed to an increase in the eye's axial length.[5]
* Refractive myopia is attributed to the condition of the refractive elements of the eye.[5] Borish further subclassified refractive myopia:[3]
* Curvature myopia is attributed to excessive, or increased, curvature of one or more of the refractive surfaces of the eye, especially the cornea.[5] In those with Cohen syndrome, myopia appears to result from high corneal and lenticular power.
* Index myopia is attributed to variation in the index of refraction of one or more of the ocular media.
Clinical entity
Various forms of myopia have been described by their clinical appearance:[4][7]
* Simple myopia is more common than other types of myopia and is characterized by an eye that is too long for its optical power (which is determined by the cornea and crystalline lens) or optically too powerful for its axial length.[8] Both genetic and environmental factors, particularly significant amounts of near work, are thought to contribute to the development of simple myopia.[8]
* Degenerative myopia, also known as malignant, pathological, or progressive myopia, is characterized by marked fundus changes, such as posterior staphyloma, and associated with a high refractive error and subnormal visual acuity after correction.[5] This form of myopia gets progressively worse over time. Degenerative myopia has been reported as one of the main causes of visual impairment.[9] Myopia with degenerative changes has been described as being very common in certain races and cultures, such as Chinese, Japanese, Korean, Arab, White, and Jewish people.[10]
* Nocturnal myopia, also known as night myopia or twilight myopia, is a condition in which the eye has a greater difficulty seeing in low illumination areas, even though its daytime vision is normal. Essentially, the eye's far point of an individual's focus varies with the level of light. Night myopia is believed to be caused by pupils dilating to let more light in, which adds aberrations resulting in becoming more nearsighted. A stronger prescription for myopic night drivers is often needed. Younger people are more likely to be affected by night myopia than the elderly.[11]
* Pseudomyopia is the blurring of distance vision brought about by spasm of the ciliary muscle.[12]
* Induced myopia, also known as acquired myopia, results from exposure to various pharmaceuticals, increases in glucose levels, nuclear sclerosis, or other anomalous conditions.[8] The encircling bands used in the repair of retinal detachments may induce myopia by increasing the axial length of the eye.[13]
* Index myopia is attributed to variation in the index of refraction of one or more of the ocular media.[5] Cataracts may lead to index myopia.[14]
* Form deprivation myopia is a type of myopia that occurs when the eye is deprived of clear form vision.[15] Myopia is often induced this way in various animal models to study the pathogenesis and mechanism of myopia development.
Degree
Myopia, which is measured in diopters by the strength or optical power of a corrective lens that focuses distant images on the retina, has also been classified by degree or severity:[2]
* Low myopia usually describes myopia of −3.00 diopters or less.[5]
* Medium myopia usually describes myopia between −3.00 and −6.00 diopters.[5] Those with moderate amounts of myopia are more likely to have pigment dispersion syndrome or pigmentary glaucoma.[16]
* High myopia usually describes myopia of −6.00 or more.[5] People with high myopia are more likely to have retinal detachments[17] and primary open angle glaucoma.[18] They are also more likely to experience floaters, shadow-like shapes which appear singly or in clusters in the field of vision.[citation needed] Roughly 30% of myopes have high myopia.
Age of onset
Myopia is sometimes classified by the age of onset:
* Congenital myopia, also known as infantile myopia, is present at birth and persists through infancy.
* Youth onset myopia occurs prior to age 20.
* School myopia appears during childhood, particularly the school-age years. This form of myopia is attributed to the use of the eyes for close work during the school years.
* Adult onset myopia
* Early adult onset myopia occurs between ages 20 and 40.[8]
* Late adult onset myopia occurs after age 40.
Epidemiology
The global prevalence of refractive errors has been estimated from 800 million to 2.3 billion.[20] The incidence of myopia within sampled population often varies with age, country, sex, race, ethnicity, occupation, environment, and other factors.[10][21] Variability in testing and data collection methods makes comparisons of prevalence and progression difficult.[22]
In some areas, such as Japan, Singapore and Taiwan, up to 44% of the adult population is myopic.[citation needed]
A recent study involving first-year undergraduate students in the United Kingdom found that 50% of British whites and 53.4% of British Asians were myopic.[23]
In Australia, the overall prevalence of myopia (worse than −0.50 diopters) has been estimated to be 77%.[24] In one recent study, less than 1 in 10 (8.4%) Australian children between the ages of 4 and 12 were found to have myopia greater than −0.50 diopters.[25] A recent review found that 16.4% of Australians aged 40 or over have at least −1.00 diopters of myopia and 2.5% have at least −5.00 diopters.[26]
In Brazil, a 2005 study estimated that 6.4% of Brazilians between the ages of 12 and 59 had −1.00 diopter or myopia or more, compared with 2.7% of the indigenous people in northwestern Brazil.[27] Another found nearly 1 in 8 (13.3%) of the students in one city were myopic.[28]
In Greece, the prevalence of myopia among 15 to 18 year old students was found to be 36.8%.
In India, the prevalence of myopia in the general population has been reported to be only 6.9%.[30][29]
A recent review found that 26.6% of Western Europeans aged 40 or over have at least −1.00 diopters of myopia and 4.6% have at least −5.00 diopters.[31]
In the United States, the prevalence of myopia has been estimated at 20%.[10] Nearly 1 in 10 (9.2%) American children between the ages of 5 and 17 have myopia.[32] Approximately 25% of Americans between the ages of 12 and 54 have the condition.[33] A recent review found that 25.4% of Americans aged 40 or over have at least −1.00 diopters of myopia and 4.5% have at least −5.00 diopters.[34]
A study of Jordanian adults aged 17 to 40 found that over half (53.7%) were myopic.[35]
Ethnicity and race
The prevalence of myopia has been reported as high as 70-90% in some Asian countries. 30-40% in Europe and the United States, and 10-20% in Africa.[21]
Myopia is less common in black and African people.[10] In Americans between the ages of 12 and 54, myopia has been found to affect blacks less than whites[33]. Asians had the highest prevalence (78.5%), followed by Hispanics (13.2%). Whites had the lowest prevalence of myopia (4.4%), which was not significantly different from African Americans (6.6%). For hyperopia, whites had the highest prevalence (19.3%), followed by Hispanics (12.7%). Asians had the lowest prevalence of hyperopia (6.3%) and were not significantly different from African Americans (6.4%). For astigmatism, Asians and Hispanics had the highest prevalences (33.6% and 36.9%, respectively) and did not differ from each other (P = .17). African Americans had the lowest prevalence of astigmatism (20.0%), followed by whites (26.4%).[36]
Education, intelligence, and IQ
A number of studies have shown that the prevalence of myopia increases with level of education and many studies have shown a relationship between myopia and IQ. However, care must be taken in interpreting these results as correlation does not imply causation.
According to Arthur Jensen, myopes average 7-8 IQ points higher than non-myopes. The relationship also holds within families, and siblings with a higher degree of refraction error average higher IQs than siblings with less refraction error. Jensen believes that this indicates myopia and IQ are pleiotropically related as they are caused or influenced by the same genes. No specific mechanism that could cause a relationship between myopia and IQ has yet been identified. Another possible explanation is that high levels of reading is a common cause for both intelligence and myopia, as it supposed that large amounts of close work is a causal factor of myopia[8].
Etiology and pathogenesis
Because in the most common, "simple" myopia, the eye length is too long, any etiologic explanation must account for such axial elongation. To date, no single theory has been able to satisfactorily explain this elongation.
In the early 1900s, controversial ophthalmologist William Bates asserted that myopia, as with all refractive errors, resulted from a particular type of "eyestrain" that was itself a result of "mental strain".[37] He stated that the shape of the eyeball responded instantaneously to the action of the extraocular muscles upon it[38] and that myopia was produced due to contraction of the inferior oblique and superior oblique muscles which lengthened the eye.[39] According to Bates, myopia was associated not with near work but with a "strain" to see distant objects; he believed that corrective lenses aggravated this strain and made myopia become progressively worse over time.[40] Encouraging his patients to discard their glasses, he advocated various techniques, now collectively known as the Bates Method, that he believed would enhance visual acuity by relaxing the eye. Although his theories were rejected by mainstream ophthalmologists of his time, and remain discredited in the profession today,[41][42] many people (including English author Aldous Huxley, who was taught by Margaret Darst Corbett, a disciple of Bates) claim to have reduced or eliminated their myopia by using his methods. However, no scientific studies have demonstrated its efficacy and the evidence supporting it remains largely anecdotal.
In the mid-1900s, mainstream ophthalmologists and optometrists believed myopia to be primarily hereditary; the influence of near work in its development seemed "incidental" and the increased prevalence of the condition with increasing age was viewed as a "statistical curiosity".[3][4][43]
Among mainstream researchers and eye care professionals, myopia is now thought to be a combination of genetic and environmental factors.[8][19]
There are currently two basic mechanisms believed to cause myopia: form deprivation (also known as pattern deprivation[44]) and optical defocus.[45] Form deprivation occurs when the image quality on the retina is reduced; optical defocus occurs when light focuses in front of or behind the retina. Numerous experiments with animals have shown that myopia can be artificially generated by inducing either of these conditions. In animal models wearing negative spectacle lenses, axial myopia has been shown to occur as the eye elongates to compensate for optical defocus.[45] The exact mechanism of this image-controlled elongation of the eye is still unknown.[citation needed] It has been suggested that accommodative lag leads to blur (i.e. optical defocus) which in turn stimulates axial elongation and myopia.[46]
Theories
* Combination of genetic and environmental factors — In China, myopia is more common in those with higher education background[47] and some studies suggest that near work may exacerbate a genetic predisposition to develop myopia.[48] Other studies have shown that near work (reading, computer games) may not be associated with myopic progression, however.[49] A "genetic susceptibility" to environmental factors has been postulated as one explanation for the varying degrees of myopia among individuals or populations,[50] but there exists some difference of opinion as to whether it exists.[19][51] High heritability simply means that most of the variation in a particular population at a particular time is due to genetic differences. If the environment changes — as, for example, it has by the introduction of televisions and computers — the incidence of myopia can change as a result, even though heritability remains high. From a slightly different point of view it could be concluded that — determined by heritage — some people are at a higher risk to develop myopia when exposed to modern environmental conditions with a lot of extensive near work like reading. In other words, it is often not the myopia itself which is inherited, but the reaction to specific environmental conditions — and this reaction can be the onset and the progression of myopia.
* Genetic factors — The wide variability of the prevalence of myopia in different ethnic groups has been reported as additional evidence supporting the role of genetics in the development of myopia.[52] Measures of the heritability of myopia have yielded figures as high as 89%, and recent research has identified genes that may be responsible: defective versions of the PAX6 gene seem to be associated with myopia in twin studies [1]. Under this theory, the eye is slightly elongated front to back as a result of faults during development, causing images to be focused in front of the retina rather than directly on it. It is usually discovered during the pre-teen years between eight and twelve years of age. It most often worsens gradually as the eye grows during adolescence and then levels off as a person reaches adulthood. Genetic factors can work in various biochemical ways to cause myopia, a weak or degraded connective tissue is a very essential one. Genetic factors include an inherited, increased susceptibility for environmental influences like excessive near work, and the fact that some people do not develop myopia in spite of very adverse conditions is a clear indication that heredity is involved somehow in any case.
* Environmental factors — It has been suggested that a genetic susceptibility to myopia does not exist.[19] A high heritability of myopia (as for any other condition) does not mean that environmental factors and lifestyle have no effect on the development of the condition. Some recommend a variety of eye exercises to strengthen the ciliary muscle. Other theories suggest that the eyes become strained by the constant extra work involved in "nearwork" and get stuck in the near position, and eye exercises can help loosen the muscles up thereby freeing it for far vision. These primarily mechanical models appear to be in contrast to research results, which show that the myopic elongation of the eye can be caused by the image quality, with biochemical processes as the actuator. Common to both views is, however, that extensive near work and corresponding accommodation can be essential for the onset and the progression of myopia.
One Austrian study confirmed that the axial length of the eye does mildly increase while reading, but attributed this elongation due to contraction of the ciliary muscle during accommodation (the process by which the eye increases optical power to maintain a clear image focus), not "squeezing" of the extraocular muscles.[53]
Near work and nightlight exposure in childhood have been hypothesized as environmental risk factors for myopia.[54] Although one initial study indicated a strong association between myopia and nightlight exposure,[55] recent research has found none.[54][56][57][58]
* Near work. Near work has been implicated as a contributing factor to myopia in some studies, but refuted in others.[59] One recent study suggested that students exposed to extensive "near work" may be at a higher risk of developing myopia, whereas extended breaks from near work during summer or winter vacations may retard myopic progression [2]. Near work in certain cultures (e.g. Vanuatu) does not result in greater myopia[3][4][5][6]. It has been hypothesized that this outcome may be a results of genetics or environmental factors such as diet or over-illumination, changes in which seem to occur in Asian, Vanuatu and Inuit cultures acclamating to intensive early studies[7].
* Diet and nutrition - One 2002 article suggested that myopia may be caused by over-consumption of bread in childhood, or in general by diets too rich in carbohydrates, which can lead to chronic hyperinsulinemia. Various other components of the diet, however, were made responsible for contributing to myopia as well, as summarized in a documentation.
* Stress has been postulated as a factor in the development of myopia.[60]
Relevant research
* A Turkish study found that accommodative convergence, rather than accommodation, may be a factor in the onset and progression of myopia in adults.[61]
* A recent Polish study revealed that "with-the-rule astigmatism" may lead to the creation of myopia.[62]
Presbyopia and the 'payoff' for the nearsighted
Many people with myopia are able to read comfortably without eyeglasses even in advanced age. Myopes considering refractive surgery are advised that this may be a disadvantage after the age of 40 when the eyes become presbyopic and lose their ability to accommodate or change focus.
Diagnosis
A diagnosis of myopia is typically confirmed during an eye examination by an ophthalmologist or an optometrist. Frequently an autorefractor or retinoscope is used to give an initial objective assessment of the refractive status of each eye, then a phoropter is used to subjectively refine the patient's eyeglass prescription.
Treatment, management, and prevention
Glasses are commonly used to address short-sightedness.
Eyeglasses, contact lenses, and refractive surgery are the primary options to treat the visual symptoms of those with myopia. Orthokeratology is the practice of using special rigid contact lenses to flatten the cornea to reduce myopia.
Eye-exercises and biofeedback
Practitioners and advocates of alternative therapies often recommend eye exercises and relaxation techniques such as the Bates method. However, the efficacy of these practices is disputed by scientists and eye care practitioners.[41] A 2005 review of scientific papers on the subject concluded that there was "no clear scientific evidence" that eye exercises were effective in treating myopia.[42]
In the eighties and nineties, there was a flurry of interest in biofeedback as a possible treatment for myopia. A 1997 review of this biofeedback research concluded that "controlled studies to validate such methods ... have been rare and contradictory."[63] It was found in one study that myopes could improve their visual acuity with biofeedback training, but that this improvement was "instrument-specific" and did not generalise to other measures or situations.[64] In another study an "improvement" in visual acuity was found but the authors concluded that this could be a result of subjects learning the task.[65] Finally, in an evaluation of a training system designed to improve acuity, "no significant difference was found between the control and experimental subjects".[66]
Prevention
There is no universally accepted method of preventing myopia.[8] Some clinicians and researchers recommend plus power (convex) lenses in the form of single vision reading lenses or bifocals.[8][67] A recent Malaysian study reported in New Scientist[68] suggested that undercorrection of myopia caused more rapid progression of myopia,[69] However, the reliability of this data has been called into question.[70] Many myopia treatment studies suffer from any of a number of design drawbacks: small numbers, lack of adequate control group, failure to mask examiners from knowledge of treatments used, etc.
Pirenzepine eyedrops had a limited effect on retarding myopic progression in a recent, placebo-control, double-blinded prospective controlled study.[71]
Myopia control
Various methods have been employed in an attempt to decrease the progression of myopia.[45] Altering the use of eyeglasses between full-time, part-time, and not at all does not appear to alter myopia progression.[72][73] Bifocal and progressive lenses have not shown significant differences in altering the progression of myopia.[45]
Myopia as metaphor
The terms myopia and myopic (or the common terms short sightedness or short sighted) have also been used metaphorically to refer to cognitive thinking and decision making that is narrow sighted or lacking in concern for wider interests or longer-term consequences.
Migraine reference
Migraine is a neurological syndrome characterized by altered bodily experiences, painful headaches, and nausea. It is a common condition which affects women more frequently than it does men.
The typical migraine headache is one-sided and pulsating, lasting 4 to 72 hours[1]. Accompanying complaints are nausea and vomiting, and a heightened sensitivity to bright lights (photophobia) and noise (hyperacusis).[2][3][4] Approximately one third of people who experience migraine get a preceding aura, in which a patient may sense a strange light or unpleasant smell.[5] Patients often describe triggers they feel precipitate an episode of migraine, such as certain foods and beverages (like chocolate or alcohol), stress or menstruation. In some migraine types there are typical features but the headache remains absent, and in children abdominal pain may be a prominent feature.
Although the exact cause of migraine remains unknown, the most widespread theory is that it is a disorder of the serotonergic control system. Genetic factors may also contribute.[6] Studies on twins show that genes have a 60 to 65% influence on the development of migraine .[7][8] Fluctuating hormone levels show a relation to migraine in several ways: three quarters of adult migraine patients are female while migraine affects approximately equal numbers of boys and girls before puberty,[citation needed] and migraine is known to disappear during pregnancy in a substantial number of sufferers.
The treatment of migraine begins with simple painkillers for headache and anti-emetics for nausea, and avoidance of triggers if present. Specific anti-migraine drugs can be used to treat migraine. If the condition is severe and frequent enough, preventative drugs might be considered.
The word migraine is French in origin and comes from the Greek hemicrania, as does the Old English term megrim. Literally, hemicrania means "half (the) head".
Migraine without aura
This is the most commonly seen form of migraine; patients who primarily suffer from migraine without aura may also have attacks of migraine with aura. According to the International Classification of Headache Disorders[9] it is a recurrent headache disorder manifesting in attacks lasting 4–72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity and association with nausea and/or photophobia and hyperacusis. In order to diagnose migraine without aura, there must have been at least five attacks not attributable to another cause that fulfill the following criteria:
1. Headache attacks lasting 4–72 hours when untreated
2. At least two of the following characteristics:
* Unilateral location
* Pulsating quality
* Moderate or severe pain intensity
* Aggravation by or causing avoidance of routine physical activity
3. During the headache there must be at least one of the following associated symptom clusters:
* Nausea and/or vomiting
* Photophobia and hyperacusis
Where these criteria are not fully met, the problem may be classified as "probable migraine without aura" but other diagnoses such as "episodic tension type headache" must also be considered.
Migraine with aura
This is the second most commonly seen form of migraine: patients who primarily suffer from migraine with aura may also have attacks of migraine without aura. According to the International Classification of Headache Disorders[9] it is a recurrent disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5–20 minutes and last for less than 60 minutes. Headache with the features of "migraine without aura" usually follows the aura symptoms. Less commonly, the aura may occur without a subsequent headache or the headache may be non-migrainous in type.
In order to diagnose migraine with aura, there must have been at least two attacks not attributable to another cause that fulfill the following criteria:
1. Aura consisting of at least one of the following, but no muscle weakness or paralysis:
* Fully reversible visual symptoms (e.g. flickering lights, spots, lines, loss of vision)
* Fully reversible sensory symptoms (e.g. pins and needles, numbness)
* Fully reversible dysphasia (speech disturbance)
2. Aura has at least two of the following characteristics:
* Visual symptoms affecting just one side of the field of vision and/or sensory symptoms affecting just one side of the body
* At least one aura symptom develops gradually over more than 5 minutes and/or different aura symptoms occur one after the other over more than 5 minutes
* Each symptom lasts from 5–60 minutes
Where these criteria are not fully met, a diagnosis of "probable migraine with aura" may be considered, although other neurological causes must also be considered. If the picture complies with the criteria but includes one-sided muscular weakness or paralysis, a diagnosis of "sporadic hemiplegic migraine" or "familial hemiplegic migraine" should be considered.
Basilar type migraine
Basilar type migraine (BTM), formerly known as basilar artery migraine (BAM) or basilar migraine (BM), is an uncommon type of complicated migraine with symptoms that result from brainstem dysfunction. Serious episodes of BTM can lead to stroke, coma, or even death. The use of triptans and other vasoconstrictors as abortive treatments in BTM is contraindicated. Abortive treatments for BTM often focus on vasodilation and restoration of normal blood flow to the vertebrobasilar territory and subsequent return of normal brainstem function.
Familial hemiplegic migraine
Main article: Familial hemiplegic migraine
Familial hemiplegic migraine 'FHM' is a type of migraine with a possible polygenetic component. These migraine attacks may last 4–72 hours[9] and are apparently caused by ion channel mutations, three types of which have been identified to date. Patients who experience this syndrome have relatively typical migraine headaches preceded and/or accompanied by reversible limb weakness on one side as well as visual, sensory or speech difficulties. A non-familial form exists as well, "sporadic hemiplegic migraine" (SHM). It is often difficult to make the diagnosis between basilar-type migraine and hemiplegic migraine. When making the differential diagnosis is difficult, the deciding symptom is often the motor weakness or unilateral paralysis which can occur in FHM or SHM. While basilar-type migraine can present with tingling or numbness, true motor weakness and/or paralysis occur only in hemiplegic migraine.
Abdominal migraine
According to the International Classification of Headache Disorders[9] abdominal migraine is a recurrent disorder of unknown origin which occurs mainly in children. It is characterised by episodes of moderate to severe central abdominal pain lasting 1–72 hours. There is usually associated nausea and vomiting but the child is entirely well between attacks.
In order to diagnose abdominal migraine, there must be at least five attacks, not attributable to another cause, fulfilling the following criteria:
1. Attacks lasting 1–72 hours when untreated
2. Pain must have ALL of the following characteristics:
* Location in the midline, around the umbilicus or poorly localised
* Dull or 'just sore' quality
* Moderate or severe intensity
3. During an attack there must be at least two of the following:
* Loss of appetite
* Nausea
* Vomiting
* Pallor
Most children with abdominal migraine will develop migraine headache later in life and the two may co-exist during adolescence.
Acephalgic migraine
Acephalgic migraine is a neurological syndrome. It is a variant of migraine in which the patient may experience aura symptoms such as scintillating scotoma, nausea, photophobia, hemiparesis and other migraine symptoms but does not experience headache. Acephalgic migraine is also referred to as amigrainous migraine, ocular migraine, or optical migraine.
Sufferers of acephalgic migraine are more likely than the general population to develop classical migraine with headache.
The prevention and treatment of acephalgic migraine is broadly the same as for classical migraine. However, because of the absence of "headache", diagnosis of acephalgic migraine is apt to be significantly delayed and the risk of misdiagnosis significantly increased.
Visual snow might be a form of acephalgic migraine.
If symptoms are primarily visual, it may be necessary to consult an ophthalmologist to rule out potential eye disease before considering this diagnosis.
Menstrual migraine
Menstrual migraine is distinct from other migraines. Approximately 21 million women in the US suffer from migraines,[11] and about 60% of them suffer from menstrual migraines.[12]
* There are two types of menstrual migraine – Menstrually Related Migraine (MRM) and Pure Menstrual Migraine (PMM)
* MRM is a headache of moderate-to-severe pain intensity that happens around the time of a woman’s period and at other times of the month as well.
* PMM is similar in every respect but only occurs around the time of a woman’s period.[13]
* The exact causes of menstrual migraine are uncertain but evidence suggest there may be a link between menstruation and migraine due to the drop in estrogen levels that normally occurs right before the period starts.[14]
* Menstrual migraine has been reported to be more likely to occur during a five-day window, from two days before to two days after menstruation.[15]
When compared with migraines that occur at other times of the month, menstrual migraines have been reported to
* Last longer—up to 72 hours[16]
* Be more severe[15][17]
* Occur more often with nausea and vomiting[12]
* Be more difficult to treat—occur more frequently
Signs and symptoms
The signs and symptoms of migraine vary among patients. Therefore, what a patient experiences before, during and after an attack cannot be defined exactly. The four phases of a migraine attack listed below are common but not necessarily experienced by all migraine sufferers. Additionally, the phases experienced and the symptoms experienced during them can vary from one migraine attack to another in the same migraineur:
1. The prodrome, which occurs hours or days before the headache.
2. The aura, which immediately precedes the headache.
3. The pain phase, also known as headache phase.
4. The postdrome.
Prodrome phase
Prodromal symptoms occur in 40 to 60% of migraineurs (migraine sufferers). This phase may consist of altered mood, irritability, depression or euphoria, fatigue, yawning, excessive sleepiness, craving for certain food (e.g. chocolate), stiff muscles (especially in the neck), constipation or diarrhea, increased urination, and other visceral symptoms. These symptoms usually precede the headache phase of the migraine attack by several hours or days, and experience teaches the patient or observant family how to detect that a migraine attack is near.
Aura phase
For the 20–30%[19][20] of individuals who suffer migraine with aura, this aura comprises focal neurological phenomena that precede or accompany the attack. They appear gradually over 5 to 20 minutes and generally last fewer than 60 minutes. The headache phase of the migraine attack usually begins within 60 minutes of the end of the aura phase, but it is sometimes delayed up to several hours, and it can be missing entirely. Symptoms of migraine aura can be visual, sensory, or motor in nature.[21]
Visual aura is the most common of the neurological events. There is a disturbance of vision consisting usually of unformed flashes of white and/or black or rarely of multicolored lights (photopsia) or formations of dazzling zigzag lines (scintillating scotoma; often arranged like the battlements of a castle, hence the alternative terms "fortification spectra" or "teichopsia"). Some patients complain of blurred or shimmering or cloudy vision, as though they were looking through thick or smoked glass, or, in some cases, tunnel vision and hemianopsia. The somatosensory aura of migraine consists of digitolingual or cheiro-oral paresthesias, a feeling of pins-and-needles experienced in the hand and arm as well as in the nose-mouth area on the same side. Paresthesia migrate up the arm and then extend to involve the face, lips and tongue.
Other symptoms of the aura phase can include auditory or olfactory hallucinations, temporary dysphasia, vertigo, tingling or numbness of the face and extremities, and hypersensitivity to touch.
Pain phase
The typical migraine headache is unilateral, throbbing, moderate to severe and can be aggravated by physical activity. Not all of these features are necessary. The pain may be bilateral at the onset or start on one side and become generalized, and usually alternates sides from one attack to the next. The onset is usually gradual. The pain peaks and then subsides, and usually lasts between 4 and 72 hours in adults and 1 and 48 hours in children. The frequency of attacks is extremely variable, from a few in a lifetime to several times a week, and the average migraineur experiences from one to three headaches a month. The head pain varies greatly in intensity.
The pain of migraine is invariably accompanied by other features. Nausea occurs in almost 90 percent of patients, while vomiting occurs in about one third of patients. Many patients experience sensory hyperexcitability manifested by photophobia, phonophobia, osmophobia and seek a dark and quiet room. Blurred vision, nasal stuffiness, diarrhea, polyuria, pallor or sweating may be noted during the headache phase. There may be localized edema of the scalp or face, scalp tenderness, prominence of a vein or artery in the temple, or stiffness and tenderness of the neck. Impairment of concentration and mood are common. Lightheadedness, rather than true vertigo and a feeling of faintness may occur. The extremities tend to be cold and moist.
Postdrome phase
The patient may feel tired, "washed out", irritable, or listless and may have impaired concentration, scalp tenderness or mood changes. Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise. Often, some of the minor headache phase symptoms may continue, such as loss of appetite, photophobia, and lightheadedness. On some patients, a 5 to 6 hour nap may reduce the pain, but slight headaches may still occur when standing or sitting quickly. Normally these symptoms go away after a good night's rest.
Diagnosis
Migraines are underdiagnosed[22] and misdiagnosed.[23] The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":
* 5 or more attacks
* 4 hours to 3 days in duration
* 2 or more of - unilateral location, pulsating quality, moderate to severe pain, aggravation by or avoidance of routine physical activity
* 1 or more accompanying symptoms - nausea and/or vomiting, photophobia, phonophobia
For migraine with aura, only two attacks are required to justify the diagnosis.
The mnemonic POUNDing (Pulsating, duration of 4–72 hOurs, Unilateral, Nausea, Disabling) can help diagnose migraine. If 4 of the 5 criteria are met, then the positive likelihood ratio for diagnosing migraine is 24.[24]
The presence of either disability, nausea or sensitivity, can diagnose migraine with:[25]
* sensitivity of 81%
* specificity of 75%
Pathophysiology
Migraines were once thought to be initiated exclusively by problems with blood vessels. The vascular theory of migraines is now considered secondary to brain dysfunction[26] and claimed to have been discredited by others.[27]
The effects of migraine may persist for some days after the main headache has ended. Many sufferers report a sore feeling in the area where the migraine was, and some report impaired thinking for a few days after the headache has passed.
Migraine headaches can be a symptom of hypothyroidism
Depolarization theory
A phenomenon known as cortical spreading depression can cause migraines.[28] In cortical spreading depression, neurological activity is depressed over an area of the cortex of the brain. This situation results in the release of inflammatory mediators leading to irritation of cranial nerve roots, most particularly the trigeminal nerve, which conveys the sensory information for the face and much of the head.
This view is supported by neuroimaging techniques, which appear to show that migraine is primarily a disorder of the brain (neurological), not of the blood vessels (vascular). A spreading depolarization (electrical change) may begin 24 hours before the attack, with onset of the headache occurring around the time when the largest area of the brain is depolarized. A French study in 2007, using the Positron Emission Tomography (PET) technique identified the hypothalamus as being critically involved in the early stages
Vascular theory
Migraines can begin when blood vessels in the brain contract and expand inappropriately. This may start in the occipital lobe, in the back of the brain, as arteries spasm. The reduced flow of blood from the occipital lobe triggers the aura that some individuals who have migraines experience because the visual cortex is in the occipital area.[26]
When the constriction stops and the blood vessels dilate, they become too wide. The once solid walls of the blood vessels become permeable and some fluid leaks out. This leakage is recognized by pain receptors in the blood vessels of surrounding tissue. In response, the body supplies the area with chemicals which cause inflammation. With each heart beat, blood passes through this sensitive area causing a throb of pain.[26]
The vascular theory of migraines is now seen as secondary to brain dysfunction
Serotonin theory
Serotonin is a type of neurotransmitter, or "communication chemical" which passes messages between nerve cells. It helps to control mood, pain sensation, sexual behaviour, sleep, as well as dilation and constriction of the blood vessels among other things. Serotonin levels in the brain may lead to a process of constriction and dilation of the blood vessels which trigger a migraine.[26] Triptans activate serotonin receptors to stop a migraine attack.[26]
Neural theory
When certain nerves or an area in the brain stem become irritated, a migraine begins. In response to the irritation, the body releases chemicals which cause inflammation of the blood vessels. These chemicals cause further irritation of the nerves and blood vessels and results in pain. Substance P is one of the substances released with first irritation. Pain then increases because substance P aids in sending pain signals to the brain.
Unifying theory
Both vascular and neural influences cause migraines.
1. stress triggers changes in the brain
2. these changes cause serotonin to be released
3. blood vessels constrict
4. chemicals including substance P irritate nerves and blood vessels causing pain
Epidemiology
Age-Gender Incidence
Age-Gender Incidence
Migraine is an extremely common condition which will affect 12–28% of people at some point in their lives.[30] However this figure — the lifetime prevalence — does not provide a very clear picture of how many patients there are with active migraine at any one time. Typically, therefore, the burden of migraine in a population is assessed by looking at the one-year prevalence — a figure that defines the number of patients who have had one or more attacks in the previous year. The third figure, which helps to clarify the picture, is the incidence — this relates to the number of first attacks occurring at any given age and helps understanding of how the disease grows and shrinks over time.
Based on the results of a number of studies, one year prevalence of migraine ranges from 6–15% in adult men and from 14–35% in adult women.[30] These figures vary substantially with age: approximately 4–5% of children aged under 12 suffer from migraine, with little apparent difference between boys and girls.[31] There is then a rapid growth in incidence amongst girls occurring after puberty,[32][33][34] which continues throughout early adult life.[35] By early middle age, around 25% of women experience a migraine at least once a year, compared with fewer than 10% of men.[30][36] After menopause, attacks in women tend to decline dramatically, so that in the over 70s there are approximately equal numbers of male and female sufferers, with prevalence returning to around 5%.[30][36]
At all ages, migraine without aura is more common than migraine with aura, with a ratio of between 1.5:1 and 2:1.[37][38] Incidence figures show that the excess of migraine seen in women of reproductive age is mainly due to migraine without aura.[37] Thus in pre-pubertal and post-menopausal populations, migraine with aura is somewhat more common than amongst 15–50 year olds.[35][39]
There is a strong relationship between age, gender and type of migraine.[40]
Geographical differences in migraine prevalence are not marked. Studies in Asia and South America suggest that the rates there are relatively low,[41][42] but they do not fall outside the range of values seen in European and North American studies.
The incidence of migraine is related to the incidence of epilepsy in families, with migraine twice as prevalent in family members of epilepsy sufferers, and more common in epilepsy sufferers themselves
Triggers
A migraine trigger is any factor that, on exposure or withdrawal, leads to the development of an acute migraine headache. Triggers may be categorized as behavioral, environmental, infectious, dietary, chemical, or hormonal. In the medical literature, these factors are known as 'precipitants.'
The MedlinePlus Medical Encyclopedia, for example, offers the following list of migraine triggers:
Migraine attacks may be triggered by:
* Allergic reactions
* Bright lights, loud noises, and certain odors or perfumes
* Physical or emotional stress
* Changes in sleep patterns
* Smoking or exposure to smoke
* Skipping meals
* Alcohol
* Menstrual cycle fluctuations, birth control pills, hormone fluctuations during the menopause transition
* Tension headaches
* Foods containing tyramine (red wine, aged cheese, smoked fish, chicken livers, figs, and some beans), monosodium glutamate (MSG) or nitrates (like bacon, hot dogs, and salami)
* Other foods such as chocolate, nuts, peanut butter, avocado, banana, citrus, onions, dairy products, and fermented or pickled foods.
Food
A 2005 literature review found that the available information about dietary trigger factors relies mostly on the subjective assessments of patients.[46] Some suspected dietary trigger factors appear to genuinely promote or precipitate migraine episodes, but many other suspected dietary triggers have never been demonstrated to trigger migraines. The review authors found that alcohol, caffeine withdrawal, and missing meals are the most important dietary migraine precipitants, that dehydration deserved more attention, and that some patients report sensitivity to red wine. Little or no evidence associated notorious suspected triggers like chocolate, cheese, histamine, tyramine, nitrates, or nitrites with migraines. The artificial sweetener aspartame has not been shown to trigger headache, but in a large and definitive study monosodium glutamate (MSG) in large doses (2.5 grams) was associated with adverse symptoms including headache more often than was placebo. The review authors also note that while general dietary restriction has not been demonstrated to be an effective migraine therapy, it is beneficial for the individual to avoid what has been a definite cause of the migraine.
The National Headache Foundation has a specific list of triggers based on the tyramine theory, detailing allowed, with caution and avoid triggers
Weather
Several studies have found some migraines are triggered by changes in weather. One study noted 62% of the subjects thought weather was a factor but only 51% were sensitive to weather changes.[48] Among those whose migraines did occur during a change in weather, the subjects often picked a weather change other than the actual weather data recorded. Most likely to trigger a migraine were, in order:
1. Temperature mixed with humidity. High humidity plus high or low temperature was the biggest cause.
2. Significant changes in weather
3. Changes in barometric pressure
Another study examined the effects of warm chinook winds on migraines, with many patients reporting increased incidence of migraines immediately before and/or during the chinook winds. The number of people reporting migrainous episodes during the chinook winds was higher on high-wind chinook days. The probable cause was thought to be an increase in positive ions in the air
Head position
One study suggests that migraines can be triggered by the head being held downwards for an extended period, as when washing hair in a basin
Treatment
Conventional treatment focuses on three areas: trigger avoidance, symptomatic control, and preventive drugs. Patients who experience migraines often find that the recommended treatments are not 100% effective at preventing migraines, and sometimes may not be effective at all.
Children and adolescents, are often first given drug treatment, but the value of diet modification should not be overlooked. The simple task of starting a diet journal to help modify the intake of trigger foods like hot dogs, chocolate, cheese and ice cream could help alleviate symptoms
Abortive treatment
Migraine sufferers usually develop their own coping mechanisms for the pain of a migraine attack. Hot or cold water applied to the head, resting in a dark and silent room or ingesting caffeine at an appropriate time may be as helpful as medication for some patients
Analgesics combined with antiemetics
Anti-emetics by mouth may help relieve symtoms of nausea and help prevent vomiting, which can diminish the effectiveness of orally taken analgesia. In addition some antiemetics such as metoclopramide are prokinetics and help gastric emptying which is often impaired during episodes of migraine. In the UK there are three combination antiemetic and analgesic preparations available: MigraMax (aspirin with metoclopramide), Migraleve (paracetamol/codeine for analgesia, with buclizine as the antiemetic) and paracetamol/metoclopramide (Paramax in UK).[55] The earlier these drugs are taken in the attack, the better their effect.
Some patients find relief from taking other sedative antihistamines which have anti-nausea properties, such as Benadryl which in the US contains diphenhydramine (but a different non-sedative product in the UK).
Status migrainosus
Status migrainosus is characterized by migraine lasting more than 72 hours, with not more than four hours of relief during that period. It is generally understood that status migrainosus has been refractory to usual outpatient management upon presentation.
Treatment of status migrainosus consists of managing comorbidities (i. e. correcting fluid and electrolyte abnormalities resulting from anorexia and nausea/vomiting often accompanying status migr.), and usually administering parenteral medication to "break" (abort) the headache.
Although the literature is full of many case reports concerning treatment of status migr., first line therapy usually consists of the parenteral administration of DHE or a neuromodulator (i. e. a valproic acid derivative or topiramate), followed by the institution of a prophylactic regimen. Alternative therapies have included parenteral narcotics, intravenous lidocaine, magnesium, serotonergic antiemetics such as promethazine or chlorpromazine, and corticosteroids. The latter is often advocated in the therapy of intractable headache resulting from medication rebound.
Herbal treatment
The herbal supplement feverfew (more commonly used for migraine prevention, see below) is marketed by the GelStat Corporation as an OTC migraine abortive, administered sublingually (under the tongue) in a mixture with ginger.[56] An open-label study (funded by GelStat) found some tentative evidence of the treatment's effectiveness,[57] but no scientifically sound study has been done. Cannabis in addition to prevention, is also known to relieve pain during the onset of a migraine
Comparative studies
Regarding comparative effectiveness of these drugs used to abort migraine attacks, a 2004 placebo-controlled trial[58] reveals that high dose acetylsalicylic acid (1000 mg), sumatriptan 50 mg and ibuprofen 400 mg are equally effective at providing relief from pain, although sumatriptan was superior in terms of the more demanding outcome of rendering patients entirely free of pain and all other migraine-related symptoms.
Another randomized controlled trial, funded by the manufacturer of the study drug, found that a combination of sumatriptan 85 mg and naproxen sodium 200 mg was better than either drug alone
Preventive treatment
Preventive (also called prophylactic) treatment of migraines can be an important component of migraine management. Such treatments can take many forms, including everything from taking certain drugs or nutritional supplements, to lifestyle alterations such as increased exercise and avoidance of migraine triggers. One such book that outlines these preventative measures quite well is "7 Steps To A Healthy Brain" by Dr. Winner.
The goals of preventive therapy are to reduce the frequency, painfulness, and/or duration of migraines, and to increase the effectiveness of abortive therapy.[59] Another reason to pursue these goals is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is a common problem among migraneurs. This is believed to occur in part due to overuse of pain medications, and can result in chronic daily headache
Prescription drugs
A 2006 review article by S. Modi and D. Lowder offers some general guidelines on when a physician should consider prescribing drugs for migraine prevention:
Following appropriate management of acute migraine, patients should be evaluated for initiation of preventive therapy. Factors that should prompt consideration of preventive therapy include the occurrence of two or more migraines per month with disability lasting three or more days per month; failure of, contraindication for, or adverse events from acute treatments; use of abortive medication more than twice per week; and uncommon migraine conditions (e.g., hemiplegic migraine, migraine with prolonged aura, migrainous infarction). Patient preference and cost also should be considered.
...Therapy should be initiated with medications that have the highest levels of effectiveness and the lowest potential for adverse reactions; these should be started at low dosages and titrated slowly. A full therapeutic trial may take two to six months. After successful therapy (e.g., reduction of migraine frequency by approximately 50 percent or more) has been maintained for six to 12 months, discontinuation of preventive therapy can be considered
Trigger avoidance
Patients can attempt to identify and avoid factors that promote or precipitate migraine episodes. Moderation in alcohol and caffeine intake, consistency in sleep habits, and regular meals may be helpful. General dietary restriction has not been demonstrated to be an effective approach to treating migraine, and migraine is remarkably resistant to the placebo effect
Herbal and nutritional supplements
Butterbur
50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was shown in a controlled trial to provide 50% or more reduction in the number of migraines to 68% of participants in the 75 mg dose group, 56% in the 50 mg dose group and 49% in the placebo group after four months. Native butterbur contains some carcinogenic compounds, but a purified version, Petadolex, does not
Cannabis
Cannabis was a standard treatment for migraines from the mid-19th century until it was outlawed in the early 20th century in the USA. It has been reported to help people through an attack by relieving the nausea and dulling the head pain, as well as possibly preventing the headache completely when used as soon as possible after the onset of pre-migraine symptoms, such as aura. There is some indication that semi-regular use may reduce the frequency of attacks. Further studies are being conducted. Some migraine sufferers report that cannabis decreases throbbing and pain, especially if smoked. A pharmaceutical company is currently conducting trials of a whole cannabis extract spray for migraine
Coenzyme Q10
Supplementation of coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraines. In an open-label trial,[67] Young and Silberstein found that 61.3% of patients treated with 100 mg/day had a greater than 50% reduction in number of days with migraine, making it more effective than most prescription prophylactics. Fewer than 1% reported any side effects. A double-blind placebo-controlled trial has also found positive results
Feverfew
The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. A number of clinical trials have been carried out to test this claim, but a 2004 review article concluded that the results have been contradictory and inconclusive.[69] However, since then, more studies have been carried out.[70] As well as its prophylactic properties, feverfew is also touted as a migraine abortative.
Magnesium Citrate
Magnesium citrate has reduced the frequency of migraine in an experiment in which the magnesium citrate group received 600 mg per day oral of trimagnesium dicitrate. In weeks 9–12, the frequency of attacks was reduced by 41.6% in the magnesium citrate group and by 15.8% in the placebo group
Riboflavin
The supplement Riboflavin (also called Vitamin B2) has been shown (in a placebo-controlled trial)[72] to reduce the number of migraines, when taken at the high dose of 400 mg daily for three months
Vitamin B12
There is tentative evidence that Vitamin B12 may be effective in preventing migraines.[73] In particular, in an open-label pilot study, 1 mg of intranasal hydroxocobalamin (a form of Vitamin B12), taken daily for three months, was shown to reduce migraine frequency by 50% or more in 10 of 19 participants.[75] Although the study was not placebo-controlled, this response is larger than the typical placebo effect in migraine prophylaxis
Surgical treatments
Surgery may be used to treat migraines by severing the corrugator supercilii muscle and zygomaticotemporal nerve.[77] The treatment may reduce or eliminate headaches in some individuals.[78]
In 2005, research[79] was published indicating that in some people with a patent foramen ovale (PFO), a hole between the upper chambers of the heart, suffer from migraines which may have been caused by the PFO. The migraines reduce in frequency if the hole is patched. Several clinical trials are currently under way in an effort to determine if a causal link between PFO and migraine can be found. Early speculation as to this relationship has centered on the idea that the lungs detoxify blood as it passes through. The PFO allows uncleaned blood to go directly from the right side of the heart to the left without passing through the lungs.
Botulin toxin has been used to treat individuals with frequent or chronic migraines. Its usefulness is uncertain with evidence suggesting it is not superior to placebo treatmentand does not appear to be useful in the treatment of episodic migraine.
Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.
Noninvasive medical treatments
Transcranial Magnetic Stimulation (TMS): At the 49th Annual meeting of the American Headache Society in June 2006, scientists from Ohio State University Medical Center presented medical research on 47 candidates that demonstrated that TMS — a medically non-invasive technology for treating depression, obsessive compulsive disorder and tinnitus, among other ailments — helped to prevent and even reduce the severity of migraines among its patients. This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines.[6] In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light.[7] Their research suggests that there is a strong neurological component to migraines. A larger study will be conducted soon to better assess TMS's complete effectiveness.[84] In June 2008, a hand-held apparatus designed to apply TMS as a preemptive therapy to avert a migraine attack at the onset of the aura phase was introduced in California.[8]
Biofeedback has been used successfully by some to control migraine symptoms through training and practice.[85]
Hyperbaric oxygen therapy has been used successfully in treating migraines.[86] This suggests that sufferers might be treated during an attack with a hyperbaric chamber of some sort, such as a Gamow bag (as is done in the treatment of "The Bends" and altitude sickness).
Bruxism, clenching or grinding of teeth, especially at night, is a trigger for many migraineurs. A device called a nociceptive trigeminal inhibitor (NTI) takes advantage of a reflex limiting the force of clenching. It can be fitted by dentists and clips over the front teeth at night, preventing contact between the back teeth. It has a success rate similar to butterbur and co-enzyme Q10, although it has not been subjected to the same rigorous testing as the supplements. Massage therapy of the jaw area can also reduce such pain.
There is a speculative connection between vision correction (particular with prism eyeglasses) and migraines. Two British studies, one from 1934[87] and another from 1956[88] claimed that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism. However, both studies are subject to criticism because of sample bias, sample size, and the lack of a control group. A more recent study [9] found that precision tinted lenses may be an effective migraine treatment. (Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.)
Behavioral treatments
Many physicians believe that exercise for 15–20 minutes per day is helpful for reducing the frequency of migraines.[89]
Sleep is often a good solution if a migraine is not so severe as to prevent it, as when a person awakes the symptoms will have most likely subsided.
Diet, visualization, and self-hypnosis are also alternative treatments and prevention approaches.
Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases.[10]
In many cases where a migraine follows a particular cycle, attempting to interrupt the cycle may prolong the symptoms. Letting a headache "run its course" by not using painkillers can sometimes decrease the length of an episode. This is especially true of cases where vomiting is common, as often the headache will subside immediately after vomiting. Curbing the pain may delay vomiting, and prolong the headache.
Alternative medicine
A number of forms of alternative medicine, particularly bodywork, are used in preventing migraines.
Massage therapy and physical therapy are often very effective forms of treatment to reduce the frequency and intensity of migraines.[citation needed] However, it is important to be treated by a well-trained therapist who understands the pathophysiology of migraines. Deep massage can 'trigger' a migraine attack in a person who is not used to such treatments. It is advisable to start sessions as short in duration and then work up to longer treatments. Likewise, some migraine sufferers find relief through chiropractic care.[citation needed]
Frequent migraines can leave the sufferer with a stiff neck which can cause stress headaches that can then exacerbate the migraines. Claims have been made that Myofascial Release can relieve this tension and in doing so reduce or eliminate the stress headache element.[citation needed]
Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing.[90] Sometimes acupuncture is used to relieve the pain of an active migraine headache.[91] In one controlled trial of acupuncture with a sham control in migraine, the acupuncture was not more effective than the sham acupuncture but was more effective than delayed acupuncture.[citation needed]
Additionally acupressure is used by some for relief. For instance pressure between the thumbs and index finger to help subside headaches if the headache or migraine isn't too severe.[citation needed]
Incense and scents are shown to help. The smell and incense of peppermint and lavender have been proven to help with migraines and headaches more so than most other scents.[92] However, some scents can be a trigger factor.
Economic impact
In addition to being a major cause of pain and suffering, chronic migraine attacks are a significant source of both medical costs and lost productivity. Medical costs per migraine sufferer (mostly physician and emergency room visits) averaged $107 USD over six months in one 1988 study,[citation needed] with total costs including lost productivity averaging $313. Annual employer cost of lost productivity due to migraines was estimated at $3,309 per sufferer. Total medical costs associated with migraines in the United States amounted to one billion dollars in 1994, in addition to lost productivity estimated at thirteen to seventeen billion dollars per year. Employers may benefit from educating themselves on the effects of migraines in order to facilitate a better understanding in the workplace. The workplace model of 9–5, 5 days a week may not be viable for a migraine sufferer. With education and understanding an employer could compromise with an employee to create a workable solution for both.
Migraine and cardiovascular risks
The risk of stroke may be increased two- to threefold in migraine sufferers. Young adult sufferers and women using hormonal contraception appear to be at particular risk.[93] The mechanism of any association is unclear, but chronic abnormalities of cerebral blood vessel tone may be involved. Women who experience auras have been found to have twice the risk of strokes and heart attacks over non-aura migraine sufferers and women who do not have migraines. Migraine sufferers seem to be at risk for both thrombotic and hemorrhagic stroke as well as transient ischemic attacks.[95] Death from cardiovascular causes was higher in people with migraine with aura in a Women's Health Initiative study, but more research is needed to confirm this.
The typical migraine headache is one-sided and pulsating, lasting 4 to 72 hours[1]. Accompanying complaints are nausea and vomiting, and a heightened sensitivity to bright lights (photophobia) and noise (hyperacusis).[2][3][4] Approximately one third of people who experience migraine get a preceding aura, in which a patient may sense a strange light or unpleasant smell.[5] Patients often describe triggers they feel precipitate an episode of migraine, such as certain foods and beverages (like chocolate or alcohol), stress or menstruation. In some migraine types there are typical features but the headache remains absent, and in children abdominal pain may be a prominent feature.
Although the exact cause of migraine remains unknown, the most widespread theory is that it is a disorder of the serotonergic control system. Genetic factors may also contribute.[6] Studies on twins show that genes have a 60 to 65% influence on the development of migraine .[7][8] Fluctuating hormone levels show a relation to migraine in several ways: three quarters of adult migraine patients are female while migraine affects approximately equal numbers of boys and girls before puberty,[citation needed] and migraine is known to disappear during pregnancy in a substantial number of sufferers.
The treatment of migraine begins with simple painkillers for headache and anti-emetics for nausea, and avoidance of triggers if present. Specific anti-migraine drugs can be used to treat migraine. If the condition is severe and frequent enough, preventative drugs might be considered.
The word migraine is French in origin and comes from the Greek hemicrania, as does the Old English term megrim. Literally, hemicrania means "half (the) head".
Migraine without aura
This is the most commonly seen form of migraine; patients who primarily suffer from migraine without aura may also have attacks of migraine with aura. According to the International Classification of Headache Disorders[9] it is a recurrent headache disorder manifesting in attacks lasting 4–72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity and association with nausea and/or photophobia and hyperacusis. In order to diagnose migraine without aura, there must have been at least five attacks not attributable to another cause that fulfill the following criteria:
1. Headache attacks lasting 4–72 hours when untreated
2. At least two of the following characteristics:
* Unilateral location
* Pulsating quality
* Moderate or severe pain intensity
* Aggravation by or causing avoidance of routine physical activity
3. During the headache there must be at least one of the following associated symptom clusters:
* Nausea and/or vomiting
* Photophobia and hyperacusis
Where these criteria are not fully met, the problem may be classified as "probable migraine without aura" but other diagnoses such as "episodic tension type headache" must also be considered.
Migraine with aura
This is the second most commonly seen form of migraine: patients who primarily suffer from migraine with aura may also have attacks of migraine without aura. According to the International Classification of Headache Disorders[9] it is a recurrent disorder manifesting in attacks of reversible focal neurological symptoms that usually develop gradually over 5–20 minutes and last for less than 60 minutes. Headache with the features of "migraine without aura" usually follows the aura symptoms. Less commonly, the aura may occur without a subsequent headache or the headache may be non-migrainous in type.
In order to diagnose migraine with aura, there must have been at least two attacks not attributable to another cause that fulfill the following criteria:
1. Aura consisting of at least one of the following, but no muscle weakness or paralysis:
* Fully reversible visual symptoms (e.g. flickering lights, spots, lines, loss of vision)
* Fully reversible sensory symptoms (e.g. pins and needles, numbness)
* Fully reversible dysphasia (speech disturbance)
2. Aura has at least two of the following characteristics:
* Visual symptoms affecting just one side of the field of vision and/or sensory symptoms affecting just one side of the body
* At least one aura symptom develops gradually over more than 5 minutes and/or different aura symptoms occur one after the other over more than 5 minutes
* Each symptom lasts from 5–60 minutes
Where these criteria are not fully met, a diagnosis of "probable migraine with aura" may be considered, although other neurological causes must also be considered. If the picture complies with the criteria but includes one-sided muscular weakness or paralysis, a diagnosis of "sporadic hemiplegic migraine" or "familial hemiplegic migraine" should be considered.
Basilar type migraine
Basilar type migraine (BTM), formerly known as basilar artery migraine (BAM) or basilar migraine (BM), is an uncommon type of complicated migraine with symptoms that result from brainstem dysfunction. Serious episodes of BTM can lead to stroke, coma, or even death. The use of triptans and other vasoconstrictors as abortive treatments in BTM is contraindicated. Abortive treatments for BTM often focus on vasodilation and restoration of normal blood flow to the vertebrobasilar territory and subsequent return of normal brainstem function.
Familial hemiplegic migraine
Main article: Familial hemiplegic migraine
Familial hemiplegic migraine 'FHM' is a type of migraine with a possible polygenetic component. These migraine attacks may last 4–72 hours[9] and are apparently caused by ion channel mutations, three types of which have been identified to date. Patients who experience this syndrome have relatively typical migraine headaches preceded and/or accompanied by reversible limb weakness on one side as well as visual, sensory or speech difficulties. A non-familial form exists as well, "sporadic hemiplegic migraine" (SHM). It is often difficult to make the diagnosis between basilar-type migraine and hemiplegic migraine. When making the differential diagnosis is difficult, the deciding symptom is often the motor weakness or unilateral paralysis which can occur in FHM or SHM. While basilar-type migraine can present with tingling or numbness, true motor weakness and/or paralysis occur only in hemiplegic migraine.
Abdominal migraine
According to the International Classification of Headache Disorders[9] abdominal migraine is a recurrent disorder of unknown origin which occurs mainly in children. It is characterised by episodes of moderate to severe central abdominal pain lasting 1–72 hours. There is usually associated nausea and vomiting but the child is entirely well between attacks.
In order to diagnose abdominal migraine, there must be at least five attacks, not attributable to another cause, fulfilling the following criteria:
1. Attacks lasting 1–72 hours when untreated
2. Pain must have ALL of the following characteristics:
* Location in the midline, around the umbilicus or poorly localised
* Dull or 'just sore' quality
* Moderate or severe intensity
3. During an attack there must be at least two of the following:
* Loss of appetite
* Nausea
* Vomiting
* Pallor
Most children with abdominal migraine will develop migraine headache later in life and the two may co-exist during adolescence.
Acephalgic migraine
Acephalgic migraine is a neurological syndrome. It is a variant of migraine in which the patient may experience aura symptoms such as scintillating scotoma, nausea, photophobia, hemiparesis and other migraine symptoms but does not experience headache. Acephalgic migraine is also referred to as amigrainous migraine, ocular migraine, or optical migraine.
Sufferers of acephalgic migraine are more likely than the general population to develop classical migraine with headache.
The prevention and treatment of acephalgic migraine is broadly the same as for classical migraine. However, because of the absence of "headache", diagnosis of acephalgic migraine is apt to be significantly delayed and the risk of misdiagnosis significantly increased.
Visual snow might be a form of acephalgic migraine.
If symptoms are primarily visual, it may be necessary to consult an ophthalmologist to rule out potential eye disease before considering this diagnosis.
Menstrual migraine
Menstrual migraine is distinct from other migraines. Approximately 21 million women in the US suffer from migraines,[11] and about 60% of them suffer from menstrual migraines.[12]
* There are two types of menstrual migraine – Menstrually Related Migraine (MRM) and Pure Menstrual Migraine (PMM)
* MRM is a headache of moderate-to-severe pain intensity that happens around the time of a woman’s period and at other times of the month as well.
* PMM is similar in every respect but only occurs around the time of a woman’s period.[13]
* The exact causes of menstrual migraine are uncertain but evidence suggest there may be a link between menstruation and migraine due to the drop in estrogen levels that normally occurs right before the period starts.[14]
* Menstrual migraine has been reported to be more likely to occur during a five-day window, from two days before to two days after menstruation.[15]
When compared with migraines that occur at other times of the month, menstrual migraines have been reported to
* Last longer—up to 72 hours[16]
* Be more severe[15][17]
* Occur more often with nausea and vomiting[12]
* Be more difficult to treat—occur more frequently
Signs and symptoms
The signs and symptoms of migraine vary among patients. Therefore, what a patient experiences before, during and after an attack cannot be defined exactly. The four phases of a migraine attack listed below are common but not necessarily experienced by all migraine sufferers. Additionally, the phases experienced and the symptoms experienced during them can vary from one migraine attack to another in the same migraineur:
1. The prodrome, which occurs hours or days before the headache.
2. The aura, which immediately precedes the headache.
3. The pain phase, also known as headache phase.
4. The postdrome.
Prodrome phase
Prodromal symptoms occur in 40 to 60% of migraineurs (migraine sufferers). This phase may consist of altered mood, irritability, depression or euphoria, fatigue, yawning, excessive sleepiness, craving for certain food (e.g. chocolate), stiff muscles (especially in the neck), constipation or diarrhea, increased urination, and other visceral symptoms. These symptoms usually precede the headache phase of the migraine attack by several hours or days, and experience teaches the patient or observant family how to detect that a migraine attack is near.
Aura phase
For the 20–30%[19][20] of individuals who suffer migraine with aura, this aura comprises focal neurological phenomena that precede or accompany the attack. They appear gradually over 5 to 20 minutes and generally last fewer than 60 minutes. The headache phase of the migraine attack usually begins within 60 minutes of the end of the aura phase, but it is sometimes delayed up to several hours, and it can be missing entirely. Symptoms of migraine aura can be visual, sensory, or motor in nature.[21]
Visual aura is the most common of the neurological events. There is a disturbance of vision consisting usually of unformed flashes of white and/or black or rarely of multicolored lights (photopsia) or formations of dazzling zigzag lines (scintillating scotoma; often arranged like the battlements of a castle, hence the alternative terms "fortification spectra" or "teichopsia"). Some patients complain of blurred or shimmering or cloudy vision, as though they were looking through thick or smoked glass, or, in some cases, tunnel vision and hemianopsia. The somatosensory aura of migraine consists of digitolingual or cheiro-oral paresthesias, a feeling of pins-and-needles experienced in the hand and arm as well as in the nose-mouth area on the same side. Paresthesia migrate up the arm and then extend to involve the face, lips and tongue.
Other symptoms of the aura phase can include auditory or olfactory hallucinations, temporary dysphasia, vertigo, tingling or numbness of the face and extremities, and hypersensitivity to touch.
Pain phase
The typical migraine headache is unilateral, throbbing, moderate to severe and can be aggravated by physical activity. Not all of these features are necessary. The pain may be bilateral at the onset or start on one side and become generalized, and usually alternates sides from one attack to the next. The onset is usually gradual. The pain peaks and then subsides, and usually lasts between 4 and 72 hours in adults and 1 and 48 hours in children. The frequency of attacks is extremely variable, from a few in a lifetime to several times a week, and the average migraineur experiences from one to three headaches a month. The head pain varies greatly in intensity.
The pain of migraine is invariably accompanied by other features. Nausea occurs in almost 90 percent of patients, while vomiting occurs in about one third of patients. Many patients experience sensory hyperexcitability manifested by photophobia, phonophobia, osmophobia and seek a dark and quiet room. Blurred vision, nasal stuffiness, diarrhea, polyuria, pallor or sweating may be noted during the headache phase. There may be localized edema of the scalp or face, scalp tenderness, prominence of a vein or artery in the temple, or stiffness and tenderness of the neck. Impairment of concentration and mood are common. Lightheadedness, rather than true vertigo and a feeling of faintness may occur. The extremities tend to be cold and moist.
Postdrome phase
The patient may feel tired, "washed out", irritable, or listless and may have impaired concentration, scalp tenderness or mood changes. Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise. Often, some of the minor headache phase symptoms may continue, such as loss of appetite, photophobia, and lightheadedness. On some patients, a 5 to 6 hour nap may reduce the pain, but slight headaches may still occur when standing or sitting quickly. Normally these symptoms go away after a good night's rest.
Diagnosis
Migraines are underdiagnosed[22] and misdiagnosed.[23] The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":
* 5 or more attacks
* 4 hours to 3 days in duration
* 2 or more of - unilateral location, pulsating quality, moderate to severe pain, aggravation by or avoidance of routine physical activity
* 1 or more accompanying symptoms - nausea and/or vomiting, photophobia, phonophobia
For migraine with aura, only two attacks are required to justify the diagnosis.
The mnemonic POUNDing (Pulsating, duration of 4–72 hOurs, Unilateral, Nausea, Disabling) can help diagnose migraine. If 4 of the 5 criteria are met, then the positive likelihood ratio for diagnosing migraine is 24.[24]
The presence of either disability, nausea or sensitivity, can diagnose migraine with:[25]
* sensitivity of 81%
* specificity of 75%
Pathophysiology
Migraines were once thought to be initiated exclusively by problems with blood vessels. The vascular theory of migraines is now considered secondary to brain dysfunction[26] and claimed to have been discredited by others.[27]
The effects of migraine may persist for some days after the main headache has ended. Many sufferers report a sore feeling in the area where the migraine was, and some report impaired thinking for a few days after the headache has passed.
Migraine headaches can be a symptom of hypothyroidism
Depolarization theory
A phenomenon known as cortical spreading depression can cause migraines.[28] In cortical spreading depression, neurological activity is depressed over an area of the cortex of the brain. This situation results in the release of inflammatory mediators leading to irritation of cranial nerve roots, most particularly the trigeminal nerve, which conveys the sensory information for the face and much of the head.
This view is supported by neuroimaging techniques, which appear to show that migraine is primarily a disorder of the brain (neurological), not of the blood vessels (vascular). A spreading depolarization (electrical change) may begin 24 hours before the attack, with onset of the headache occurring around the time when the largest area of the brain is depolarized. A French study in 2007, using the Positron Emission Tomography (PET) technique identified the hypothalamus as being critically involved in the early stages
Vascular theory
Migraines can begin when blood vessels in the brain contract and expand inappropriately. This may start in the occipital lobe, in the back of the brain, as arteries spasm. The reduced flow of blood from the occipital lobe triggers the aura that some individuals who have migraines experience because the visual cortex is in the occipital area.[26]
When the constriction stops and the blood vessels dilate, they become too wide. The once solid walls of the blood vessels become permeable and some fluid leaks out. This leakage is recognized by pain receptors in the blood vessels of surrounding tissue. In response, the body supplies the area with chemicals which cause inflammation. With each heart beat, blood passes through this sensitive area causing a throb of pain.[26]
The vascular theory of migraines is now seen as secondary to brain dysfunction
Serotonin theory
Serotonin is a type of neurotransmitter, or "communication chemical" which passes messages between nerve cells. It helps to control mood, pain sensation, sexual behaviour, sleep, as well as dilation and constriction of the blood vessels among other things. Serotonin levels in the brain may lead to a process of constriction and dilation of the blood vessels which trigger a migraine.[26] Triptans activate serotonin receptors to stop a migraine attack.[26]
Neural theory
When certain nerves or an area in the brain stem become irritated, a migraine begins. In response to the irritation, the body releases chemicals which cause inflammation of the blood vessels. These chemicals cause further irritation of the nerves and blood vessels and results in pain. Substance P is one of the substances released with first irritation. Pain then increases because substance P aids in sending pain signals to the brain.
Unifying theory
Both vascular and neural influences cause migraines.
1. stress triggers changes in the brain
2. these changes cause serotonin to be released
3. blood vessels constrict
4. chemicals including substance P irritate nerves and blood vessels causing pain
Epidemiology
Age-Gender Incidence
Age-Gender Incidence
Migraine is an extremely common condition which will affect 12–28% of people at some point in their lives.[30] However this figure — the lifetime prevalence — does not provide a very clear picture of how many patients there are with active migraine at any one time. Typically, therefore, the burden of migraine in a population is assessed by looking at the one-year prevalence — a figure that defines the number of patients who have had one or more attacks in the previous year. The third figure, which helps to clarify the picture, is the incidence — this relates to the number of first attacks occurring at any given age and helps understanding of how the disease grows and shrinks over time.
Based on the results of a number of studies, one year prevalence of migraine ranges from 6–15% in adult men and from 14–35% in adult women.[30] These figures vary substantially with age: approximately 4–5% of children aged under 12 suffer from migraine, with little apparent difference between boys and girls.[31] There is then a rapid growth in incidence amongst girls occurring after puberty,[32][33][34] which continues throughout early adult life.[35] By early middle age, around 25% of women experience a migraine at least once a year, compared with fewer than 10% of men.[30][36] After menopause, attacks in women tend to decline dramatically, so that in the over 70s there are approximately equal numbers of male and female sufferers, with prevalence returning to around 5%.[30][36]
At all ages, migraine without aura is more common than migraine with aura, with a ratio of between 1.5:1 and 2:1.[37][38] Incidence figures show that the excess of migraine seen in women of reproductive age is mainly due to migraine without aura.[37] Thus in pre-pubertal and post-menopausal populations, migraine with aura is somewhat more common than amongst 15–50 year olds.[35][39]
There is a strong relationship between age, gender and type of migraine.[40]
Geographical differences in migraine prevalence are not marked. Studies in Asia and South America suggest that the rates there are relatively low,[41][42] but they do not fall outside the range of values seen in European and North American studies.
The incidence of migraine is related to the incidence of epilepsy in families, with migraine twice as prevalent in family members of epilepsy sufferers, and more common in epilepsy sufferers themselves
Triggers
A migraine trigger is any factor that, on exposure or withdrawal, leads to the development of an acute migraine headache. Triggers may be categorized as behavioral, environmental, infectious, dietary, chemical, or hormonal. In the medical literature, these factors are known as 'precipitants.'
The MedlinePlus Medical Encyclopedia, for example, offers the following list of migraine triggers:
Migraine attacks may be triggered by:
* Allergic reactions
* Bright lights, loud noises, and certain odors or perfumes
* Physical or emotional stress
* Changes in sleep patterns
* Smoking or exposure to smoke
* Skipping meals
* Alcohol
* Menstrual cycle fluctuations, birth control pills, hormone fluctuations during the menopause transition
* Tension headaches
* Foods containing tyramine (red wine, aged cheese, smoked fish, chicken livers, figs, and some beans), monosodium glutamate (MSG) or nitrates (like bacon, hot dogs, and salami)
* Other foods such as chocolate, nuts, peanut butter, avocado, banana, citrus, onions, dairy products, and fermented or pickled foods.
Food
A 2005 literature review found that the available information about dietary trigger factors relies mostly on the subjective assessments of patients.[46] Some suspected dietary trigger factors appear to genuinely promote or precipitate migraine episodes, but many other suspected dietary triggers have never been demonstrated to trigger migraines. The review authors found that alcohol, caffeine withdrawal, and missing meals are the most important dietary migraine precipitants, that dehydration deserved more attention, and that some patients report sensitivity to red wine. Little or no evidence associated notorious suspected triggers like chocolate, cheese, histamine, tyramine, nitrates, or nitrites with migraines. The artificial sweetener aspartame has not been shown to trigger headache, but in a large and definitive study monosodium glutamate (MSG) in large doses (2.5 grams) was associated with adverse symptoms including headache more often than was placebo. The review authors also note that while general dietary restriction has not been demonstrated to be an effective migraine therapy, it is beneficial for the individual to avoid what has been a definite cause of the migraine.
The National Headache Foundation has a specific list of triggers based on the tyramine theory, detailing allowed, with caution and avoid triggers
Weather
Several studies have found some migraines are triggered by changes in weather. One study noted 62% of the subjects thought weather was a factor but only 51% were sensitive to weather changes.[48] Among those whose migraines did occur during a change in weather, the subjects often picked a weather change other than the actual weather data recorded. Most likely to trigger a migraine were, in order:
1. Temperature mixed with humidity. High humidity plus high or low temperature was the biggest cause.
2. Significant changes in weather
3. Changes in barometric pressure
Another study examined the effects of warm chinook winds on migraines, with many patients reporting increased incidence of migraines immediately before and/or during the chinook winds. The number of people reporting migrainous episodes during the chinook winds was higher on high-wind chinook days. The probable cause was thought to be an increase in positive ions in the air
Head position
One study suggests that migraines can be triggered by the head being held downwards for an extended period, as when washing hair in a basin
Treatment
Conventional treatment focuses on three areas: trigger avoidance, symptomatic control, and preventive drugs. Patients who experience migraines often find that the recommended treatments are not 100% effective at preventing migraines, and sometimes may not be effective at all.
Children and adolescents, are often first given drug treatment, but the value of diet modification should not be overlooked. The simple task of starting a diet journal to help modify the intake of trigger foods like hot dogs, chocolate, cheese and ice cream could help alleviate symptoms
Abortive treatment
Migraine sufferers usually develop their own coping mechanisms for the pain of a migraine attack. Hot or cold water applied to the head, resting in a dark and silent room or ingesting caffeine at an appropriate time may be as helpful as medication for some patients
Analgesics combined with antiemetics
Anti-emetics by mouth may help relieve symtoms of nausea and help prevent vomiting, which can diminish the effectiveness of orally taken analgesia. In addition some antiemetics such as metoclopramide are prokinetics and help gastric emptying which is often impaired during episodes of migraine. In the UK there are three combination antiemetic and analgesic preparations available: MigraMax (aspirin with metoclopramide), Migraleve (paracetamol/codeine for analgesia, with buclizine as the antiemetic) and paracetamol/metoclopramide (Paramax in UK).[55] The earlier these drugs are taken in the attack, the better their effect.
Some patients find relief from taking other sedative antihistamines which have anti-nausea properties, such as Benadryl which in the US contains diphenhydramine (but a different non-sedative product in the UK).
Status migrainosus
Status migrainosus is characterized by migraine lasting more than 72 hours, with not more than four hours of relief during that period. It is generally understood that status migrainosus has been refractory to usual outpatient management upon presentation.
Treatment of status migrainosus consists of managing comorbidities (i. e. correcting fluid and electrolyte abnormalities resulting from anorexia and nausea/vomiting often accompanying status migr.), and usually administering parenteral medication to "break" (abort) the headache.
Although the literature is full of many case reports concerning treatment of status migr., first line therapy usually consists of the parenteral administration of DHE or a neuromodulator (i. e. a valproic acid derivative or topiramate), followed by the institution of a prophylactic regimen. Alternative therapies have included parenteral narcotics, intravenous lidocaine, magnesium, serotonergic antiemetics such as promethazine or chlorpromazine, and corticosteroids. The latter is often advocated in the therapy of intractable headache resulting from medication rebound.
Herbal treatment
The herbal supplement feverfew (more commonly used for migraine prevention, see below) is marketed by the GelStat Corporation as an OTC migraine abortive, administered sublingually (under the tongue) in a mixture with ginger.[56] An open-label study (funded by GelStat) found some tentative evidence of the treatment's effectiveness,[57] but no scientifically sound study has been done. Cannabis in addition to prevention, is also known to relieve pain during the onset of a migraine
Comparative studies
Regarding comparative effectiveness of these drugs used to abort migraine attacks, a 2004 placebo-controlled trial[58] reveals that high dose acetylsalicylic acid (1000 mg), sumatriptan 50 mg and ibuprofen 400 mg are equally effective at providing relief from pain, although sumatriptan was superior in terms of the more demanding outcome of rendering patients entirely free of pain and all other migraine-related symptoms.
Another randomized controlled trial, funded by the manufacturer of the study drug, found that a combination of sumatriptan 85 mg and naproxen sodium 200 mg was better than either drug alone
Preventive treatment
Preventive (also called prophylactic) treatment of migraines can be an important component of migraine management. Such treatments can take many forms, including everything from taking certain drugs or nutritional supplements, to lifestyle alterations such as increased exercise and avoidance of migraine triggers. One such book that outlines these preventative measures quite well is "7 Steps To A Healthy Brain" by Dr. Winner.
The goals of preventive therapy are to reduce the frequency, painfulness, and/or duration of migraines, and to increase the effectiveness of abortive therapy.[59] Another reason to pursue these goals is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is a common problem among migraneurs. This is believed to occur in part due to overuse of pain medications, and can result in chronic daily headache
Prescription drugs
A 2006 review article by S. Modi and D. Lowder offers some general guidelines on when a physician should consider prescribing drugs for migraine prevention:
Following appropriate management of acute migraine, patients should be evaluated for initiation of preventive therapy. Factors that should prompt consideration of preventive therapy include the occurrence of two or more migraines per month with disability lasting three or more days per month; failure of, contraindication for, or adverse events from acute treatments; use of abortive medication more than twice per week; and uncommon migraine conditions (e.g., hemiplegic migraine, migraine with prolonged aura, migrainous infarction). Patient preference and cost also should be considered.
...Therapy should be initiated with medications that have the highest levels of effectiveness and the lowest potential for adverse reactions; these should be started at low dosages and titrated slowly. A full therapeutic trial may take two to six months. After successful therapy (e.g., reduction of migraine frequency by approximately 50 percent or more) has been maintained for six to 12 months, discontinuation of preventive therapy can be considered
Trigger avoidance
Patients can attempt to identify and avoid factors that promote or precipitate migraine episodes. Moderation in alcohol and caffeine intake, consistency in sleep habits, and regular meals may be helpful. General dietary restriction has not been demonstrated to be an effective approach to treating migraine, and migraine is remarkably resistant to the placebo effect
Herbal and nutritional supplements
Butterbur
50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was shown in a controlled trial to provide 50% or more reduction in the number of migraines to 68% of participants in the 75 mg dose group, 56% in the 50 mg dose group and 49% in the placebo group after four months. Native butterbur contains some carcinogenic compounds, but a purified version, Petadolex, does not
Cannabis
Cannabis was a standard treatment for migraines from the mid-19th century until it was outlawed in the early 20th century in the USA. It has been reported to help people through an attack by relieving the nausea and dulling the head pain, as well as possibly preventing the headache completely when used as soon as possible after the onset of pre-migraine symptoms, such as aura. There is some indication that semi-regular use may reduce the frequency of attacks. Further studies are being conducted. Some migraine sufferers report that cannabis decreases throbbing and pain, especially if smoked. A pharmaceutical company is currently conducting trials of a whole cannabis extract spray for migraine
Coenzyme Q10
Supplementation of coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraines. In an open-label trial,[67] Young and Silberstein found that 61.3% of patients treated with 100 mg/day had a greater than 50% reduction in number of days with migraine, making it more effective than most prescription prophylactics. Fewer than 1% reported any side effects. A double-blind placebo-controlled trial has also found positive results
Feverfew
The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. A number of clinical trials have been carried out to test this claim, but a 2004 review article concluded that the results have been contradictory and inconclusive.[69] However, since then, more studies have been carried out.[70] As well as its prophylactic properties, feverfew is also touted as a migraine abortative.
Magnesium Citrate
Magnesium citrate has reduced the frequency of migraine in an experiment in which the magnesium citrate group received 600 mg per day oral of trimagnesium dicitrate. In weeks 9–12, the frequency of attacks was reduced by 41.6% in the magnesium citrate group and by 15.8% in the placebo group
Riboflavin
The supplement Riboflavin (also called Vitamin B2) has been shown (in a placebo-controlled trial)[72] to reduce the number of migraines, when taken at the high dose of 400 mg daily for three months
Vitamin B12
There is tentative evidence that Vitamin B12 may be effective in preventing migraines.[73] In particular, in an open-label pilot study, 1 mg of intranasal hydroxocobalamin (a form of Vitamin B12), taken daily for three months, was shown to reduce migraine frequency by 50% or more in 10 of 19 participants.[75] Although the study was not placebo-controlled, this response is larger than the typical placebo effect in migraine prophylaxis
Surgical treatments
Surgery may be used to treat migraines by severing the corrugator supercilii muscle and zygomaticotemporal nerve.[77] The treatment may reduce or eliminate headaches in some individuals.[78]
In 2005, research[79] was published indicating that in some people with a patent foramen ovale (PFO), a hole between the upper chambers of the heart, suffer from migraines which may have been caused by the PFO. The migraines reduce in frequency if the hole is patched. Several clinical trials are currently under way in an effort to determine if a causal link between PFO and migraine can be found. Early speculation as to this relationship has centered on the idea that the lungs detoxify blood as it passes through. The PFO allows uncleaned blood to go directly from the right side of the heart to the left without passing through the lungs.
Botulin toxin has been used to treat individuals with frequent or chronic migraines. Its usefulness is uncertain with evidence suggesting it is not superior to placebo treatmentand does not appear to be useful in the treatment of episodic migraine.
Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.
Noninvasive medical treatments
Transcranial Magnetic Stimulation (TMS): At the 49th Annual meeting of the American Headache Society in June 2006, scientists from Ohio State University Medical Center presented medical research on 47 candidates that demonstrated that TMS — a medically non-invasive technology for treating depression, obsessive compulsive disorder and tinnitus, among other ailments — helped to prevent and even reduce the severity of migraines among its patients. This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines.[6] In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light.[7] Their research suggests that there is a strong neurological component to migraines. A larger study will be conducted soon to better assess TMS's complete effectiveness.[84] In June 2008, a hand-held apparatus designed to apply TMS as a preemptive therapy to avert a migraine attack at the onset of the aura phase was introduced in California.[8]
Biofeedback has been used successfully by some to control migraine symptoms through training and practice.[85]
Hyperbaric oxygen therapy has been used successfully in treating migraines.[86] This suggests that sufferers might be treated during an attack with a hyperbaric chamber of some sort, such as a Gamow bag (as is done in the treatment of "The Bends" and altitude sickness).
Bruxism, clenching or grinding of teeth, especially at night, is a trigger for many migraineurs. A device called a nociceptive trigeminal inhibitor (NTI) takes advantage of a reflex limiting the force of clenching. It can be fitted by dentists and clips over the front teeth at night, preventing contact between the back teeth. It has a success rate similar to butterbur and co-enzyme Q10, although it has not been subjected to the same rigorous testing as the supplements. Massage therapy of the jaw area can also reduce such pain.
There is a speculative connection between vision correction (particular with prism eyeglasses) and migraines. Two British studies, one from 1934[87] and another from 1956[88] claimed that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism. However, both studies are subject to criticism because of sample bias, sample size, and the lack of a control group. A more recent study [9] found that precision tinted lenses may be an effective migraine treatment. (Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.)
Behavioral treatments
Many physicians believe that exercise for 15–20 minutes per day is helpful for reducing the frequency of migraines.[89]
Sleep is often a good solution if a migraine is not so severe as to prevent it, as when a person awakes the symptoms will have most likely subsided.
Diet, visualization, and self-hypnosis are also alternative treatments and prevention approaches.
Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases.[10]
In many cases where a migraine follows a particular cycle, attempting to interrupt the cycle may prolong the symptoms. Letting a headache "run its course" by not using painkillers can sometimes decrease the length of an episode. This is especially true of cases where vomiting is common, as often the headache will subside immediately after vomiting. Curbing the pain may delay vomiting, and prolong the headache.
Alternative medicine
A number of forms of alternative medicine, particularly bodywork, are used in preventing migraines.
Massage therapy and physical therapy are often very effective forms of treatment to reduce the frequency and intensity of migraines.[citation needed] However, it is important to be treated by a well-trained therapist who understands the pathophysiology of migraines. Deep massage can 'trigger' a migraine attack in a person who is not used to such treatments. It is advisable to start sessions as short in duration and then work up to longer treatments. Likewise, some migraine sufferers find relief through chiropractic care.[citation needed]
Frequent migraines can leave the sufferer with a stiff neck which can cause stress headaches that can then exacerbate the migraines. Claims have been made that Myofascial Release can relieve this tension and in doing so reduce or eliminate the stress headache element.[citation needed]
Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing.[90] Sometimes acupuncture is used to relieve the pain of an active migraine headache.[91] In one controlled trial of acupuncture with a sham control in migraine, the acupuncture was not more effective than the sham acupuncture but was more effective than delayed acupuncture.[citation needed]
Additionally acupressure is used by some for relief. For instance pressure between the thumbs and index finger to help subside headaches if the headache or migraine isn't too severe.[citation needed]
Incense and scents are shown to help. The smell and incense of peppermint and lavender have been proven to help with migraines and headaches more so than most other scents.[92] However, some scents can be a trigger factor.
Economic impact
In addition to being a major cause of pain and suffering, chronic migraine attacks are a significant source of both medical costs and lost productivity. Medical costs per migraine sufferer (mostly physician and emergency room visits) averaged $107 USD over six months in one 1988 study,[citation needed] with total costs including lost productivity averaging $313. Annual employer cost of lost productivity due to migraines was estimated at $3,309 per sufferer. Total medical costs associated with migraines in the United States amounted to one billion dollars in 1994, in addition to lost productivity estimated at thirteen to seventeen billion dollars per year. Employers may benefit from educating themselves on the effects of migraines in order to facilitate a better understanding in the workplace. The workplace model of 9–5, 5 days a week may not be viable for a migraine sufferer. With education and understanding an employer could compromise with an employee to create a workable solution for both.
Migraine and cardiovascular risks
The risk of stroke may be increased two- to threefold in migraine sufferers. Young adult sufferers and women using hormonal contraception appear to be at particular risk.[93] The mechanism of any association is unclear, but chronic abnormalities of cerebral blood vessel tone may be involved. Women who experience auras have been found to have twice the risk of strokes and heart attacks over non-aura migraine sufferers and women who do not have migraines. Migraine sufferers seem to be at risk for both thrombotic and hemorrhagic stroke as well as transient ischemic attacks.[95] Death from cardiovascular causes was higher in people with migraine with aura in a Women's Health Initiative study, but more research is needed to confirm this.
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