Subacute Sclerosing Panencephalitis

Subacute sclerosing panencephalitis is a fatal progressive encephalitis caused by persistent defective measles virus in the brain, appearing 4 to 10 years after measles infection (range 1 month to 27 years). The risk is about 1 in 10,000 after measles, and up to 1 in 600 when infection occurs before 12 months of age.

Pathophysiology. Mutant measles virus lacking envelope proteins persists in neurons and glia, with inflammation and gliosis, neurofibrillary tangles and demyelination.

Stage 1: behaviour change, declining school performance and cognitive decline. Stage 2: myoclonic jerks (periodic, every 5 to 10 seconds), seizures, dementia, ataxia and chorioretinitis or optic atrophy. Stage 3: rigidity, coma and autonomic failure. Stage 4: akinetic mutism, a vegetative state and death, usually within 1 to 3 years, though a fulminant course occurs.

Red flags.

• Myoclonus with cognitive decline in a child or young adult with prior measles.
• Visual loss with macular lesions.

CSF measles antibody titres raised, with a high CSF to serum ratio and oligoclonal bands, are the key finding. EEG shows periodic high amplitude complexes with burst suppression. MRI shows periventricular and subcortical white matter changes, later atrophy. Measles RNA by PCR in CSF or brain tissue may be positive. Biopsy is rarely needed.

Differential diagnosis.

• Creutzfeldt-Jakob disease, autoimmune encephalitis and Rasmussen encephalitis.
• Progressive rubella panencephalitis, neuronal ceroid lipofuscinosis and other leukodystrophies.
• Epilepsy with regression and mitochondrial disease.

There is no cure.

Antiviral and immune therapy. Combination treatment may slow progression in some patients: oral isoprinosine (inosine pranobex) 100 mg/kg daily in divided doses, with interferon alfa 2b given intrathecally or intraventricularly, under specialist supervision. Ribavirin intraventricular therapy has been used in selected cases. Benefit is modest.

Seizures and myoclonus. Sodium valproate 10 to 15 mg/kg daily in divided doses, increased to 30 to 60 mg/kg daily (monitor liver function and platelets), and clonazepam 0.01 to 0.03 mg/kg daily in divided doses, increased cautiously. Carbamazepine helps myoclonus in some.

Supportive care. Nutrition (gastrostomy), spasticity treatment, secretion control, physiotherapy, family support and palliative care.

Prevention. Measles vaccination, and immunisation of contacts to protect infants who are too young to be vaccinated.

Monitoring. Seizure control, nutrition, aspiration risk and quality of life.

Referral and escalation. Refer to paediatric neurology and palliative care services.