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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

The clinical spectrum associated with NMDAR-Abs includes adult and children, male and female, paraneoplastic and non-paraneoplastic patients (with and without tumour)

About

• Autoimmune encephalitis. 80% of patients are women
• An immunotherapy-responsive panencephalitis
• May present before the cancer and cause severe neurological disability
• First seen in young women with ovarian teratomata

Aetiology

• Response to NMDA receptor 1 (NR1) subunit of the NMDA receptor
• NMDA receptors (NMDARs) are ion channels gated by glutamate
• Gutmate is the major excitatory neurotransmitter in the CNS
• Antibodies found in CSF and serum
• Antibodies reduce NMDA receptors on hippocampal neurons
• There is Cell mediated immunity attack on neurones

NDMAR encephalitis first appeared in medical literature in 2005 when four women were found to have similar presentations that mimicked either an acute psychotic episode, recent drug use, or malingering

Clinical

• Progressive psychiatric onset and a later movement disorder
• Progressive dementia, psychosis, epilepsy
• Occasionally can occur without cancer
• Catatonia, impaired attention, dyskinesias, and seizures
• Autonomic dysfunction (hypertension, hyperthermia, tachycardia, and hypoventilation)

Investigation

• FBC, U&E, LFT, CRP
• MRI changes but may be unremarkable
• CT CAP to look for malignancy
• CSF: lymphocytic pleocytosis or oligoclonal bands with normal to elevated CSF protein. CSF Glucose is also normal.
• EEG: generally reveal nonspecific abnormalities such as diffuse slowing. They may reveal extreme versions of the ‘delta brush pattern’, which are transient patterns characterized by a slow delta wave with superimposed fast activity.
• Found to have N-methyl-D-aspartate receptor (NMDAR) antibody
• Screen for teratoma or germ cell tumour

Differentials

• Schizophrenia
• Psychotic spectrum disorders
• Substance-induced psychosis
• Limbic encephalitis
• Paraneoplastic encephalitides
• Systemic lupus erythematosus
• Antiphospholipid syndromes
• Sjögren’s syndrome
• Graves’ disease
• Hashimoto’s encephalitis
• Vasculitis

Management

• ABC, supportive, haloperidol/Lorazepam for behaviour
• Some suggest IVIg (0.3 g/kg per day for 5 days) and methylprednisolone (1 g/day for 5 days) over plasma exchange. If patients show minimal improvement, the next line of therapy is immunosuppression, using rituximab or cyclophosphamide, with continued immunosuppression (mycophenolate mofetil or azathioprine) for at least 1 year
• Levetiracetam for seizure control
• Tumour removal where possible. Steroids may help
• Those without malignancy can make full recovery

References

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