Makindo Medical Notes

Related Subjects: |Anti-NMDA (NMDAR) receptor encephalitis |Herpes Simplex Encephalitis (HSV) |Acute Encephalitis |Limbic Encephalitis |Paraneoplastic Limbic Encephalitis (Dementia) |Hashimoto's (Steroid responsive) Encephalopathy |Acute Disseminated Encephalomyelitis

Note: Anti-NMDA receptor (NMDAR) encephalitis affects a diverse group including adults, children, both sexes, and can be paraneoplastic or non-paraneoplastic, with or without associated tumors.

About

• Autoimmune Encephalitis: A form of autoimmune panencephalitis affecting predominantly young women, with 80% of cases in females.
• Immunotherapy-Responsive: Responds to immunotherapy but can cause severe neurological disability if untreated.
• Paraneoplastic Association: First identified in young women with ovarian teratomas, but can occur in the absence of cancer.

Aetiology

• Antibody-Mediated Attack: Caused by antibodies targeting the NMDA receptor 1 (NR1) subunit on neurons.
• NMDA Receptor Role: These receptors, gated by glutamate (the main excitatory neurotransmitter in the CNS), are crucial for synaptic plasticity, learning, and memory.
• Pathogenesis: Antibodies reduce NMDA receptor density on hippocampal neurons, impairing function and inducing inflammation.
• Immune Response: Involves both antibody-mediated and cell-mediated immune responses against neurons.

History: Anti-NMDAR encephalitis was first described in 2005, with cases presenting as acute psychosis, drug intoxication, or malingering, and often misdiagnosed initially.

Clinical Features

• Initial Symptoms: Progressive psychiatric symptoms including anxiety, hallucinations, paranoia, and changes in personality.
• Movement Disorder: Dyskinesias, choreoathetosis, or catatonia develop as the disease progresses.
• Cognitive and Neurological Symptoms: Progressive dementia, psychosis, and epilepsy are common, along with autonomic dysfunction (e.g., hypertension, tachycardia, hyperthermia, hypoventilation).
• Seizures: Frequently present, and often resistant to treatment.
• Non-Cancer Cases: Occurs without malignancy in some cases, particularly in younger individuals and men.

Investigations

• Blood Tests: FBC, U&E, LFT, and CRP are often within normal limits but used to assess general health.
• MRI Brain: May show changes but can be unremarkable in some cases.
• CT of Chest, Abdomen, and Pelvis (CAP): Performed to look for an underlying tumor, especially ovarian teratoma.
• CSF Analysis: Typically shows lymphocytic pleocytosis or oligoclonal bands, with normal to elevated protein and normal glucose levels.
• EEG: Shows nonspecific abnormalities, commonly diffuse slowing. Extreme delta brush pattern (delta waves with superimposed fast activity) may be observed.
• Antibody Testing: Detection of NMDAR antibodies in CSF or serum confirms the diagnosis.

Differential Diagnoses

• Psychiatric Disorders: Schizophrenia, psychotic spectrum disorders, and substance-induced psychosis.
• Other Autoimmune Encephalitides: Limbic encephalitis, paraneoplastic encephalitis.
• Autoimmune Diseases: Systemic lupus erythematosus, antiphospholipid syndrome, Sjögren's syndrome, Graves' disease, Hashimoto's encephalitis.
• Vasculitis: Particularly CNS vasculitis.

Management

• Initial Supportive Care: ABC stabilization, with haloperidol or lorazepam as needed for behavioral symptoms.
• First-Line Immunotherapy: IVIg (0.3 g/kg per day for 5 days) and methylprednisolone (1 g/day for 5 days) are commonly used initially, with plasma exchange as an alternative.
• Second-Line Immunotherapy: For patients with minimal improvement, rituximab or cyclophosphamide may be used. Long-term immunosuppression (mycophenolate mofetil or azathioprine) is typically continued for at least one year.
• Seizure Control: Levetiracetam is often used for managing seizures.
• Tumor Removal: Surgical resection of any identified tumor, especially ovarian teratomas, may lead to significant improvement.
• Prognosis: Non-paraneoplastic cases generally have a good prognosis, with potential for full recovery; however, some neurological symptoms may persist in severe cases.

References

• Anti-NMDA receptor encephalitis: a case study and illness overview (2019)
• Anti-NMDA receptor encephalitis: a review of mechanistic studies