AUTOIMMUNE ENCEPHALITIS

Autoimmune encephalitis (AIE) includes many clinical syndromes associated with antibodies against neuronal cell surface proteins and intracellular antigens. In ~50% cases, exact antigen and specific antibodies are not yet identified (seronegative AIE).

While exact trigger for development of these anti­bodies is unknown, many cases are associated with tumors (paraneoplastic) or preceding viral-like illness (parainfectious). AIE of paraneoplastic origin is uncommon in children.

Some important autoimmune encephalitis are as follows:

Acute disseminated encephalomyelitis (ADEM) is the commonest non-infective encephalopathy in children, presenting with acute onset multifocal neurological deficits, due to diffuse and extensive demyelination of brain and spinal cord.

Etiologically, ADEM is considered as an autoimmune response to preceding viral infections or vaccines. Most cases present after 1-2 weeks of non-specific infections, e.g. influenza, varicella, enteroviruses, measles, mumps, rubella, etc. or some vaccinations, e.g. rabies, MMR, DPT, influenza, etc.

Clinically more common 5-8 years age-group, ADEM generally presents with low-grade fever, headache and vomiting, followed by gradual onset of altered sensorium and focal neurological deficits. Seizures, visual loss, cranial neuropathies and bladder/bowel dysfunction may be present.

Diagnosis rests on MRI showing large, multifocal edematous mass-like tumefactive lesions in white matter though gray matter and spinal cord may also be involved (Fig. 18.13). Lesions typically appear to be of same age but their evolution may lag behind the clinical presentation.

CSF is normal or may reveal mild lymphocytic pleocy­tosis. About 10-20% cases have other CSF abnormalities, e.g. oligoclonal bands, raised immune globulin levels or antibodies against myelin oligodendrocyte glycoprotein or aquaporin-4 antigen.

EEG often shows generalized slowing with/without focal epileptiform discharges.

Fig. 18.13: Acute disseminated encephalomyelitis.

Treatment includes supportive management like anticonvulsants along with high-dose IV methylpredniso­lone (20-30 mg/kg/day ? 5 days) followed by PO pre­dnisolone (1-2 mg/kg/day) in tapering doses for 3 month. Other options include IV immunoglobulin (1 gm/kg/day ? 2 days) or plasmapheresis. In severe cases, Rituximab may be considered.

Outcome: Most cases recover fully while some are left with residual motor or cognitive deficits. Repeat MRI after 3 months often shows near-complete resolution of radiological changes (except gliosis). Appearance of new clinical signs or MRI lesions beyond 3 months suggests possibility of alternate diagnosis, e.g. multiple sclerosis.

Anti-n-methyl-d-aspartate receptor encephalitis (ANMDAR encephalitis) is the second commonest cause of autoimmune encephalitis after ADEM in children and adolescents.

Etiologically associated with presence of antibodies against NR1 subunit of the NMDA receptor, these cases may be associated with an underlying tumor, e.g. teratoma or infections, e.g. Mycoplasma, HSV and influenza.

Clinically, more common in adolescent girls, ANMDAR encephalitis usually presents with progressive behavioral manifestations, e.g. anxiety, agitation, delusion and bizarre behavior, often misdiagnosed as psychiatric disorder. Additional symptoms develop in few days/ weeks, including altered sensorium, seizures, dyskinesia, choreoathetoid movements and autonomic instability.

Younger cases often present with complex seizures and movement disorders as psychiatric-behavioral features are missed in them.

Diagnosis rests on presence of NMDAR antibodies in CSF or serum. MRI is abnormal in ~35% cases, usually with bilateral symmetrical densities in temporoparietal

regions on T2 or FLAIR-weighted images.

While sometimes it is difficult to differentiate it with viral encephalitis, presence of high fever and significant pleocytosis in CSF favours viral etiology.

Management involves removal of tumor (if any), along with immunotherapy with corticosteroids, IVIG, or plasma exchange. Rituximab and cyclophosphamide may be used as second-line alternatives.

Outcome: With mortality rate is lt;10%, most cases recover substantially, though recovery may be slow, taking 1-2 years. Relapse may occur in ~15% cases.

Rasmussen encephalitis is a rare encephalopathy, usually seen in early school children, characterized by progressive refractory partial seizures, cognitive deterioration and focal deficits with hemiatrophy of cerebral hemisphere. Etiology is unknown, may be related to presence of antibodies against the GluR3 subunit of the AMPA receptor, triggered by a viral infection. Immunosuppressive therapy may be useful in some cases, though the definitive treatment is functional hemispherectomy with surgical disconnection of the affected hemisphere.

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