| Subacute sclerosing panencephalitis | |
|---|---|
| Other names | Dawson disease |
 | |
| Subacute sclerosing panencephalitis. | |
| Specialty | Neurology,Infectious Disease |
| Symptoms | Behavior changes,seizures,spasticity,poor coordination,coma |
| Usual onset | 6–15 years after infection with measles |
| Causes | Measles virus |
| Risk factors | Measles infection |
| Diagnostic method | EEG, Serologic testing, brain biopsy |
| Prevention | Measles vaccine |
| Treatment | Supportive treatment |
| Medication | Intrathecal interferon alpha, intravenous ribavirin, isoprinosine |
| Prognosis | Usually fatal |
| Frequency | 2 in 10,000 for all age groups;[1] as high as 1 in 609 for unvaccinated infants under 15 months[2] |
Subacute sclerosing panencephalitis (SSPE), also known asDawson disease, is a rare form of progressivebrain inflammation caused by a persistent infection with themeasles virus. The condition primarily affects children, teens, and young adults. It has been estimated that about 2 in 10,000 people who get measles will eventually develop SSPE.[1] However, a 2016 study estimated that the rate for unvaccinated infants under 15 months was as high as 1 in 609.[2][3] No cure for SSPE exists, and the condition is almost always fatal. SSPE should not be confused withacute disseminated encephalomyelitis, which can also be caused by the measles virus, but has a very different timing and course.[4]
SSPE is caused by somestrains of thewild-type (naturally occurring) measles virus, such as the B3 strain,[5] but not by the strains used in measles vaccines.[6][5]
SSPE is characterized by a history of primarymeasles infection, followed by a normal, unremarkable recovery.[5] Symptoms of SSPE appear later.[5]On average, the first symptoms appear about 10 years after the initial infection, though this varies significantly, as some people have developed SSPE symptoms as soon as 1 month after infection, and others as long as 27 years later.[5]
After the asymptomatic period, progressiveneurological deterioration occurs, characterized by behavior change, intellectual problems,myoclonic seizures, blindness,ataxia, and eventually death.[7][8]
The very earliest symptoms are small, subtle changes in behavior, such as not paying attention or struggling with schoolwork.[9] By the time family members have become concerned, the disease is at Stage 1, and showsnonspecific symptoms of neurological problems, such as being more irritable than usual, more affectionate than usual,lethargic, or havingspeech difficulties.[9] Because the symptoms are nonspecific, it this stage it may be obvious to people who know the child well that something is wrong, but unclear what the problem is.
Later symptoms are not subtle. They includemyoclonic seizures,epileptic seizures,loss of vision,loss of coordination, and difficulty moving.[9]
There are multiple staging systems. Symptoms progress through four stages, such as these:[10][11]
SSPE is caused by alatent infection by mutated copies ofwild type (naturally occurring) measles virus.[5] A large number ofnucleocapsids are produced in theneurons and theglial cells. In these cells the viralgenes that encodeenvelope proteins have restricted expression.[12] As a result, infectious particles like theM protein are not produced, and the virus is able to survive persistently without evoking an immune response. Eventually the infection will lead to SSPE.[13]
When SSPE begins, itdemyelinates nerves, causing them to signal unreliably.[9] Later, thebrain cortex atrophies, and theventricular system becomes dilated.[9] Nerve cells are destroyed throughphagocytosis.[9]Tauopathies andneurofibrillary tangles develop.[9]
SSPE may be suspected in any child with symptoms of aprogressive (keeps getting worse)neurological disease and who has never been vaccinated against measles.[9]
Typical diagnostic tests includeelectroencephalography (EEG) to look for evidence of epilepsy or other disturbances to brain waves and atest of the cerebrospinal fluid to look for elevated levels ofantibodies against measles and to rule outmultiple sclerosis.[9]Magnetic resonance imaging (MRI) of the brain usually looks normal early in the disease.[9]
There is no cure.[14] Most treatments aresupportive measures, such asanticonvulsants to reduce seizures.[8]
If the diagnosis is made early, oralisoprinosine (Inosiplex) is standard,[9] but it is expensive and only stabilizes or improves symptoms for about 30% of people with SSPE.[5] Less effective medications include intraventricularinterferon alfa,amantadine,ribavirin, and others.[5]Immunoglobulin therapy (IVIG) is also used.[9] Isoprinosine is sometimes combined with interferon alfa.[5][9]
Following onset of stage 2, the disease is invariably fatal.
SSPE is a disease for which prevention is the best medicine.[5][9] SSPE can be prevented byvaccinating children against measles before they become infected.[5] The strain of measles virus in the measles vaccines do not cause SSPE.[5]
Almost everyone who develops SSPE dies as a result of SSPE orsecondary complications.[5] Commonly, the person dies within a few months to a few years.[5] Faster deterioration in cases of acute fulminant SSPE can lead to death within 3 months of diagnosis.[15][16] This faster progression may be calledmeasles inclusion body encephalitis.[9]
Although the prognosis is bleak for SSPE past stage 1, there is a 5%spontaneous remission rate. This may take the form of either a full remission of symptoms that may last many years, or an improvement in condition, giving a longer progression period, or else at least a longer period with the less severe symptoms.[16][17]
If a remission is achieved, the subsequent relapse is untreatable.[18]
The number of people who develop SSPE depends on the number of people who get sick with measles.[5] For every 100,000 children or adults who get measles, between 4 and 11 of them will develop SSPE.[5] An outbreak of measles within any community is "inevitably" followed by an uptick in SSPE among the people (usually children) who had been infected with measles.[9]
The chance of developing SSPE is higher for babies (about 1 in 600 infected babies will later develop SSPE) than for those who had measles when they were older.[5] Boys develop SSPE about three times as often as girls.[9]
SSPE is a rare condition, although there is still relatively high incidence in Asia and the Middle East. However, the number of reported cases is declining since the introduction of the measles vaccine. Eradication of the measles virus prevents the SSPE mutation and therefore the progression of the disease, or even the initial infection itself.[19]
SSPE was first described by James R. Dawson, Jr. of theVanderbilt University School of Medicine in 1933.[9]
The initial symptoms of SSPE are subtle and include mild mental deterioration (such as memory loss) and changes in behavior (such as irritability) followed by disturbances in motor function, including uncontrollable involuntary jerking movements of the head, trunk or limbs called myoclonic jerks. Seizures may also occur. Some people may become blind. In advanced stages of the disease, individuals may lose the ability to walk, as their muscles stiffen or spasm. There is progressive deterioration to a comatose state, and then to a persistent vegetative state. Death is usually the result of fever, heart failure, or the brain's inability to continue controlling the autonomic nervous system.