Subacute sclerosing leukoencephalitis (ORPHA:2806)
A rare infectious disease characterized by slowly progressive brain disorder caused by a mutant measles virus, typically affecting children and young adults. The condition leads to cognitive decline, myoclonus, vision loss, and eventually a vegetative state.
Epidemiology
The global burden of subacute sclerosing leukoencephalitis (SSPE) is greater in countries with high measles incidence. According to the WHO, there is one case of SSPE every 9,090 to 25,000 measles cases, increasing to one SSPE case every 5,555 measles cases in early childhood. Higher incidences are reported in resource-constrained countries such as India, Pakistan, Papua New Guinea, and Turkey. In high-income countries, fewer cases are seen due to vaccination efforts, though outbreaks can still lead to new SSPE cases. Additionally, the risk of SSPE is twice as high in males.
Clinical description
In children, SSPE starts with cognitive decline, poor school performance, forgetfulness, behavioral changes, and gait abnormalities. Verbal output diminishes, progressing to akinesia and mutism. Patients develop pyramidal signs, periodic myoclonus, and eventually enter a vegetative state with autonomic instability. Ophthalmological symptoms, such as chorioretinitis and vision loss, may precede neurological signs. SSPE is almost always lethal. Diagnosis is supported by characteristic electroencephalogram (EEG) findings and elevated measles antibody titers in the cerebrospinal fluid.
Etiology
SSPE results from mutant measles virus entry during acute infection. Mutations in the virus genome, particularly in the M and F genes, enable viral persistence and transneuronal spread. The virus enters the brain via infected monocytes, endothelial cells, or the olfactory bulb. Hyperfusogenic properties due to changes in the F protein and defective M protein facilitate viral survival and spread, with genetic susceptibility influencing disease development.
Diagnostic methods
EEG reveals characteristic periodic discharges, while neuroimaging shows periventricular white matter abnormalities and significant cerebral atrophy in advanced stages. Diagnosis is confirmed by elevated measles antibody titers in cerebrospinal fluid.
Differential diagnosis
The differential diagnosis of SSPE includes autoimmune encephalopathies, vitamin B12 deficiency, herpes simplex encephalitis, neurosyphilis, and progressive multifocal leukoencephalopathy in HIV patients. Misdiagnosis can involve psychiatric disorders, autoimmune encephalitis, eclampsia, brain tumors, and acute disseminated encephalomyelitis, potentially leading to incorrect treatments.
Management and treatment
Universal measles vaccination has significantly reduced the incidence of SSPE. However, treatment remains challenging, with no proven effective therapies currently available. Although various drugs, such as isoprinosine, interferon-alpha, and ribavirin, are used to manage SSPE, there is a lack of randomized clinical trials to support their efficacy. About 6% of patients may experience extended spontaneous remission. Future treatments might involve fusion inhibitor peptides, but universal measles vaccination remains the only proven preventive measure.
Prognosis
SSPE is almost always lethal, typically within 1-3 years, with ~60% of patients surviving less than 2 years. Survival rates vary, with some cases experiencing prolonged remission of up to 18 years. In cases of fulminant SSPE, death occurs rapidly, often within 6 months.

                            Last update: 
                            July 2024


                            - Expert reviewer(s): 
                            Pr Ravindra Kumar GARG