Subacute Sclerosing Panencephalitis

Subacute Sclerosing Panencephalitis (SSPE)

1. Subacute sclerosing panencephalitis Ade Wijaya, MD – August 2019

2. Definition P rogressive and fatal neurodegenerative encephalitis caused by the persistence of the measles virus in the central nervous system (CNS) Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

3. Epidemiology Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

4. Risk Factors Measles contracted under 5 years of age has highest risk of developing subacute sclerosing panencephalitis ( SSPE ) Children with, or exposed to, human immunodeficiency virus infection , who contract measles may be at increased risk of SSPE Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

5. Pathophysiology Mutations that alter viral envelope glycoproteins, in particular the F protein, are responsible for neurovirulence Measles virus is believed to enter the brain during the primary infection By remaining in cells, the virus evades the host’s immune response Strong antiviral immune responses in the host are evidenced by high levels of specific antibody in blood and cerebrospinal fluid Griffin DE. Measles virus and the nervous system . Handb Clin Neurol 2014; 123 : 577 – 90. Sato Y, Watanabe S, Fukuda Y, Hashiguchi T, Yanagi Y, Ohno S. Cell-to-cell measles virus spread between human neurons is dependent on hemagglutinin and hyperfusogenic fusion protein. J Virol 2018; 92 : e02166 – 17. Watanabe S, Ohno S, Shirogane Y, Suzuki SO, Koga R, Yanagi Y. Measles virus mutants possessing the fusion protein with enhanced fusion activity spread effectively in neuronal cells, but not in other cells, without causing strong cytopathology. J Virol 2015; 89 : 2710 – 17.

6. Clinical Course SSPE typically begins with behavioural and intellectual disability followed by paroxysmal movements, myoclonic jerks , and/or negative myoclonia (head drops ) Periodic myoclonus often leads to difficulty in walking and repeated falls The myoclonic jerks are generalized and involve the head, trunk, and limbs, they do not interfere with consciousness, and are exacerbated by the state of excitement Clinical manifestations occur, on average , 6 years after measles virus infection and progressive neurological deterioration with death generally occuring within 4 years ( range 45d–12y) Other complications , reported in case reports and series, include ophthalmological abnormalities (optic atrophy) and pyramidal signs Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

7. Lakshmi V, Malathy Y, Rao RR. Serodiagnosis of subacute sclerosing panencephalitis by enzyme linked immunosorbent assay. Indian J Pediatr 1993; 60 : 37 – 41. Ozt € urk A, G € urses C, Baykan B, G € okyigit A, Eraksoy M. Subacute sclerosing panencephalitis: clinical and magnetic resonance imaging evaluation of 36 patients . J Child Neurol 2002; 17 : 25 – 9.

8. Dyken’s modified criteria MAJOR Clinical history Elevated CSF measles antibody titres MINOR T ypical EEG I ncreased CSF immunoglobulin G (IgG) Brain biopsy Special molecular diagnostic tests to identify measles virus mutated genome 2 Major + 1 Minor Criteria Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis : an update. Dev Med Child Neurol 2010 ; 52 : 901 – 7.

9. EEG Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

10. Management A life-threatening disease with no cure Generally, death occurs within 4 years Isoprinosine monotherapy and isoprinosine plus ribavirin were the standard treatments, but also intravenous immunoglobulin therapy, intrathecal a-interferon ( a-IFN ), and amantadine therapy Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

11. Symptomatic treatment Spasticity: baclofen Myoclonic and seizure: valproate, carbamazepine, clonazepam Mekki M, Eley B, Hardie D, Wilmshurst JM. Subacute sclerosing panencephalitis: clinical phenotype, epidemiology, and preventive interventions. Developmental Medicine & Child Neurology. 2019

12. Summary Measle related Dyken’s modified criteria Immunomodulation and antiviral agents Poor prognosis