Subacute sclerosing panencephalitis

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Subacute sclerosing panencephalitis
Classification and external resources
ICD-10 A81.1
ICD-9 046.2
OMIM 260470
DiseasesDB 12597
MedlinePlus 001419
MeSH C02.182.500.300.600

Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus (which can be a result of a mutation of the virus itself). It has been estimated that about 1 in 10,000 people infected with measles will eventually develop SSPE.[1] No cure for SSPE exists and the condition often ends fatally, but it 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).

SSPE is also known as Dawson Disease, Dawson encephalitis and measles encephalitis. It should not be confused with acute disseminated encephalomyelitis which has a similar etiology but very different timing and course.

Symptoms[edit]

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.

Pathogenesis[edit]

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.[2] So infectious particles like the M protein are not produced, thus the virus is able to survive persistently without evoking an immune response. Eventually, the infection leads to SSPE.

Progression[edit]

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. This is often accompanied by memory loss and mental deterioration characterised by intellectual difficulty. 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 dysphagia. 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 and/or comatose.

Diagnosis[edit]

Subacute sclerosing panencephalitis. Figure 1. MRI scans of the brain at the time of presentation in the neurology clinic (A and B) and 3 months later (C and D). Panels A and C are T1-weighted images; B and D are T2-weighted images. The initial MRI scan (A and B) reveals a focal abnormality in the subcortical white matter of the left frontal lobe, consisting of a hypointense signal on the T1-weighted image (arrow in A) and a hyperintense signal on the T2-weighted image (arrow in B). In the follow-up scan, the focal abnormality in the left frontal lobe is less obvious than previously (arrow in D), but advanced and diffuse cortical atrophy is present, signified by the ventriculomegaly and markedly enlarged sulci (arrowheads in C).

Characteristic periodic activity (Rademecker complex) is seen on 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 and glial cells. 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 electroencephalographs, an elevated anti-measles antibody (IgG) in the serum and cerebrospinal fluid, and typical histologic findings in brain biopsy tissue.

Prognosis[edit]

Death usually occurs within 3 years. If the diagnosis is made during stage 1 of the SSPE infection then it is possible to treat the disease. 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% remission rate—this may be either a full remission or an improvement in condition giving a longer progression period or at least a longer period with the less severe symptoms. Regardless of the stage that the infection is at, treatment with inosine pranobex combined with interferon can give up to a 50% remission/improvement rate.

Treatment[edit]

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 then 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's spread 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.

Global patterns of infection[edit]

SSPE is an incredibly 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.[citation needed]

See also[edit]

External links[edit]

Subacute sclerosing panencephalitis was featured as a diagnosis in season 1 of the medical drama House, MD, episode 2 titled "Paternity"

References[edit]

  1. ^ Bellini WJ, Rota JS, Lowe LE, Katz RS, Dyken PR, Zaki SR, Shieh WJ, Rota PA (2005). "Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized.". The Journal of Infectious Diseases 192 (10): 1686–1693. doi:10.1086/497169. PMID 16235165. 
  2. ^ Jawetz. Melnick & Adelberg's Medical Microbiology. Lange. 2010. p. 586. ISBN 978-0-07-174271-9.