Dr Ira Shah
M.D, DNB, DCH(Gold Medalist), FCPS

A 4 years old male child born of non-consanguineous marriage presented with myoclonic convulsions and tremors since 6 days which were not present in sleep. He had difficulty in walking due to same. His birth history, immunization history and milestones were normal. He had received measles vaccine. There was no history of fever rash or drug ingestion prior to the illness or in the past. On examination, the child was ataxic. There were no other cerebellar signs. He had intention myoclonus and tremors. Mentation appeared to have regressed. Other systemic examination was normal. A differential diagnosis of subacute sclerosing panencephalitis, MERRF, Ramsay Hunt disease and Lafora’s disease was considered. His MRI brain was normal. There was no evidence of KF ring and thyroid function tests were also normal. His CSF meas les IgG was positive 6.88 RFV (positive = >0.7 RFV)] and EEG was suggestive of burst suppression pattern. Thus the diagnosis of SSPE was confirmed. He was advised regarding Inosiplex; however parents were not ready for same.

Subacute Sclerosing Panencephalitis (SSPE) is rare chronic encephalitis caused by persistent measles virus infection of the central nervous system. It was first described by Dawson in 1933.

The incidence of SSPE has decreased over years since the introduction of live attenuated measles vaccine. Infact, in USA after 1982, less than 5 new cases have been registered from the entire country. Children with SSPE are more likely to have been infected with natural measles than vaccine virus. The risk of SSPE after measles is 4.0 in 1,00,000 cases as compared to a risk after measles vaccine of 0.14 in 1,00,000 cases. When measles is contracted in children younger than 1 year of age, the risk for SSPE is 16 times greater than when measles is contracted in children older than 5 years of age. The median interval between measles and onset of SSPE is 8 years.

The disease is believed to begin in the cortical grey matter progressing then to the subcortical white and grey matter (Myoclonus probably results from extrapyramidal involvement) and finally to the lower structures. It has been proposed that viral mutation may render the measles virus more likely to establish persistent CNS infection. It has also been theorized that patients with SSPE have subtle predisposing immune deficiency; the markedly increased risk of SSPE after measles in infancy suggests that either immunologic immaturity or persistence of maternal antibodies to measles virus is involved in the later occurrence of the disease. Complete measles virus particles are not found in the brains of patients with SSPE and the matrix (M) protein required for the final assembly is missing from the brain tissue resulting in accumulation of incomplete measles virus that cannot be cleared either by antibodies or by cell-mediated i mmunity. The histopathology of SSPE consists of inflammation, necrosis and repair. Intranuclear inclusion bodies surrounded by clear halos (cowdry type A) may be seen within the nuclei of neurons, astrocytes and oligodendrocytes. Demyelination is more evident in chronic cases.

Patients initially present with personality changes and deteriorating scholastic performance. Myoclonic convulsions usually appear after 2 months, initially of the head and subsequently of trunk and limbs. These myoclonic jerks disappear during sleep. Spontaneous speech and movements decrease although comprehension is well preserved. With further progression, extrapyramidal dyskinesia and spasticity become prominent. Patients may develop athetosis, chorea, ballismus and dystonic movements. Swallowing difficulties may occur. Ocular involvement is seen in 56% of patients with SSPE in form of optic neuritis, retinitis or macular pigment disturbances. The disease is characterized by slow progressive deterioration or variable periods of remission with mean duration of disease being approximately 1 year. Patients have lived for as short as 6 weeks after onset of symptoms or as long as 20 years. In the terminal stage of disease, dec erebrate rigidity with irregular respirations and signs of hypothalamic instability such as hyperthermia, profuse sweating and disturbances of pulse and blood pressure are seen.

Early in the course of disease, the electroencephalogram (EEG) may be normal or show only moderate nonspecific slowing. In the myoclonic stage, most patients with SSPE have “burst-suppression” episodes. However this pattern is not unique to SSPE. Later in the illness, EEG becomes increasingly disorganized. Diagnosis is confirmed by elevated levels of measles antibodies in the serum and CSF. CFS also shows elevated oligoclonal bands (IgG). CSF pleocytosis is absent or minimal. MRI or CT scans of patients with SSPE show variable cortical atrophy and ventricular enlargement. SSPE should be distinguished from subacute measles encephalitis with measles inclusion body encephalitis (MIBE) which occurs in children with immunocompromised cellular immunity. In this condition, CSF shows no elevation in measles antibody titers though measles virus can be demonstrated in the brain. SSPE also should be differentiated from lipid oses, progressive rubella panencephalitis and various degenerations of white matter.

No adequate treatment is currently available. Administration of inosiplex (100 mg/kg/d) may prolong survival. Administration of interferon is of uncertain benefit. Carbamazepine is recommended for myoclonus induced falling episodes. Measles vaccination is the most important measure to prevent SSPE.