Subacute sclerosing panencephalitis
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|Subacute sclerosing panencephalitis|
|Synonym||Subacute inclusion body encephalitis, Subacute sclerosing panencephalitis, Dawson disease, Dawson encephalitis, measles encephalitis|
|Symptoms||Seizures, spasticity, poor coordination, coma, photosensitivity|
|Usual onset||6-10 years after infection by measles|
|Causes||Persistent infection with the measles virus|
|Risk factors||Infection by measles usually at age below 2 years|
|Diagnostic method||EEG, brain biopsy|
|Treatment||Medications (only works at Stage 1)|
|Medication||Intrathecal interferon alpha, intravenous ribavirin|
|Frequency||About 1 in 10,000 people infected by measles |
|Subacute sclerosing panencephalitis|
|Synonyms||Subacute inclusion body encephalitis, Subacute sclerosing panencephalitis, Dawson disease, Dawson encephalitis, measles encephalitis|
|Classification and external resources|
Subacute sclerosing panencephalitis (SSPE) is a rare and chronic form of progressive brain inflammation caused by a persistent infection with measles virus (which can be a result of a mutation of the virus itself). The condition primarily affects children and young adults. It has been estimated that about 1 in 10,000 people infected with measles will eventually develop SSPE. However, a 2016 study estimated that the rate for babies who contracted measles was as high as 1 in 609. No cure for SSPE exists and the condition is often fatal. However, SSPE can be managed by medication if treatment is started at an early stage. Much of the work on SSPE has been performed by the National Institute of Neurological Disorders and Stroke (NINDS).
Signs and symptoms
Characterized by a history of primary measles infection usually before the age of 2 years, followed by several asymptomatic years (6–15 on average), and then gradual, progressive psychoneurological deterioration, consisting of personality change, seizures, myoclonus, ataxia, photosensitivity, ocular abnormalities, spasticity, and coma.
A large number of nucleocapsids are produced in the neurons and the glial cells. In these cells the viral genes that encode envelope proteins have restricted expression. As a result, infectious particles like the M protein are not produced, and the virus is able to survive persistently without evoking an immune response. Eventually the infection will lead to SSPE.
The progression of symptoms begins with stage 1—in this stage the individual's behaviour becomes more abnormal and erratic: they can be irritable and personality alterations can occur, often accompanied by dementia. As the nervous system begins to lose control of movement, the person develops myoclonic spasms/jerks (these being involuntary motions and spasms in extremities). As the disease progresses towards stage 2, the intensity of the spasms and the mental deterioration increases. The spasms can grow to such an extent that loss of the ability to walk can be a common sign. Also, the person will suffer speech impairment and increasingly deteriorated comprehension coupled with difficulty swallowing. The final, advanced stages of SSPE include the steady decline in body function with increased intensity of the stage 2 symptoms/signs and also blindness. At the end of the final stages the person is likely to be mute, in a vegetative state, and/or comatose.
Characteristic periodic activity (Rademecker complex) is seen on electroencephalogram (EEG) showing widespread cortical dysfunction; pathologically, the white matter of both the hemispheres and brainstem are affected, as well as the cerebral cortex, and eosinophilic inclusion bodies are present in the nuclei of neurons (gray matter) and oligodendrocytes (white matter). The diagnosis of SSPE is based on signs and symptoms (Changes in personality, a gradual onset of mental deterioration and myoclonia) and on test results, such as typical changes observed in EEGs, an elevated anti-measles antibody (IgG) in the serum and cerebrospinal fluid, and typical histologic findings in brain biopsy tissue.
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Should the viral progression be diagnosed during stage 1 (even during late stage 1 when stage 2 symptoms start to manifest themselves) then treatment to combat the infection can be administered successfully—there is no cure for SSPE but if it is caught early enough then the sufferer can respond to the treatment and prevent symptom recurrence by taking the medication for the rest of their life. The treatment for the SSPE infection is the immunomodulator interferon and specific antiviral medication—ribavirin and inosine pranobex are specifically used to greater effect than antivirals such as amantadine.
For those who have progressed to stage 2 or beyond, the disease is incurable. For patients in the terminal phase of the disease there is a palliative care and treatment scheme—this involves anticonvulsant therapy (to help with the body's progressive loss of control of the nervous system causing gradually more intensive spasms/convulsions) alongside supportive measures to help maintain vital functioning. It is fairly standard as the infection spreads and symptoms intensify that feeding tubes need to be inserted to keep a nutritional balance. As the disease progresses to its most advanced phase, the patient will need constant nursing as normal bodily function declines to the complete collapse of the nervous system. Combinations of treatment for SSPE include:
- Oral inosine pranobex (oral isoprinosine) combined with intrathecal (injection through a lumbar puncture into the spinal fluid) or intraventricular interferon alpha.
- Oral inosine pranobex (oral isoprinosine) combined with interferon beta.
- Intrathecal interferon alpha combined with intravenous ribavirin.
In the classic presentation of the disease death usually occurs within 3 years, however there are rarely both fast and slower progressions. Faster deterioration in cases of acute fulminant SSPE leads to death within 3 months of diagnosis.
If the diagnosis is made during stage 1 of the SSPE infection then it may be possible to treat the disease with oral isoprinosine (Inosiplex) and intraventricular interferon alfa, but the response to these drugs varies from patient to patient. However, once SSPE progresses to stage 2 then it is universally fatal in all occurrences. The standard rate of decline spans anywhere between 1–3 years after the onset of the infection. The progression of each stage is unique to the sufferer and cannot be predicted although the pattern or symptoms/signs can be.
Although the prognosis is bleak for SSPE past stage 1, there is a 5% spontaneous remission rate—this may be either a full remission that may last many years or an improvement in condition giving a longer progression period or at least a longer period with the less severe symptoms.
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.
Society and culture
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- subacute_panencephalitis at NINDS
- PubMed Health: Subacute sclerosing panencephalitis
- synd/1889 at Who Named It?