All patients referred for NMDAR antibody testing must have been discussed with or reviewed by a neurologist, the name of the neurologist must appear on the request form. Testing will be deferred on all specimens where it is unclear if a neurology review has occurred or not. Deferred and/or urgent requests should be discussed directly with a laboratory based Clinical Immunologist.
Neuronal antibody request form
Note: Ideally paired serum and CSF specimens should be sent together for testing.
Unpaired CSF and serum specimens will be processed.
3.5 mL SST Serum (Preferred) 4 mL Plain Serum 2 mL Paediatric Microsample Serum 1 mL Sterile Container CSF Turnaround Time: Within 1 day
- Testing only performed Monday to Friday
- Specimens in the department for testing before 10.30 will be processed the same day.
- Any specimens arriving in the department after 10.30 will be processed the next day.
Euroimmun indirect immunofluorescent assay
Diagnostic Use and Interpretation
Anti-NMDAR encephalitis is an autoimmune based syndrome with a progressive clinical course that can be treated. The syndrome affects females in a ratio of 4:1 over males, most commonly but not exclusively occurring in young females of reproductive age (1). In approximately 60% of cases, there is an underlying tumour (often unidentified); ovarian being the commonest (2).
The clinical presentation can be broken down into four phases:
1. Prodromal phase
In approximately 70% of patients the encephalitis commences with somewhat non-specific symptoms of fever, malaise, poor concentration, headaches, nausea, vomiting and diarrhoea. This phase lasts from one to three weeks (3).
The remaining phases can vary both in terms of sequence and severity.
2. Psychotic and / or seizure phase
Patients undergo behavioural and emotional changes including fear, apathy, depression, decreased cognitive skills and psychosis (4). Ataxia and choreiform movements may be noted (5). Seizures (tonic-clonic) may also occur; the severity and management of which may require admission to intensive care facilities where monitored settings for cardiac and respiratory support are available.
3. Unresponsive phase
Patients are unable to follow verbal commands and may appear mute. Other symptoms can include maintaining gaze as if in a catatonic state, smiling inappropriately and stereotyped athetotic movements of the hands and fingers (6).
4. Hyperkinetic phase
This phase is characterised by autonomic instability manifesting with cardiac arrhythmia, hypotension, hypertension, hyperventilation, hyperthermia and hypothermia. Dyskinesias, extra-pyramidal signs and stereotyped motor automatisms (lip smacking, teeth clenching, grimacing, sustained jaw movements and oculogyric crisis) may be observed (7). Autonomic dysregulation is more common in adults, whereas speech dysfunction is more common in children (4).
Once the diagnosis of anti-NMDAR encephalitis is confirmed, aggressive treatment using immunosuppression, IVIG, anti-inflammatory agents, plasma exchange and monoclonal antibodies (rituximab) directed against CD-20 B lymphocytes either sequentially or in combination is given (6).
With prompt aggressive treatment the prognosis is good with approximately 75% of affected patients experiencing complete or near complete recovery (3) . In the setting of delayed or ineffective treatment, mortality rates can exceed 90% (1).
Relapses can occur in 20-25% of patients at intervals ranging from three months to nine years after the initial presentation (8). Commonest symptoms of relapsing patients include speech dysfunction, psychiatric symptoms, seizures and disturbances of consciousness and attention. Relapse rates are highest in patients not treated with immunotherapeutics in the first episode and those where tumour resection was not performed (3, 9).
Recently, a cell-based assay was developed using HEK293 cells transfected with the cDNA representing the single or assembled NR1-NR2 subunits of the N-terminal domain from the glutamate receptor. By using a cell based assay approach, the conformational integrity of the subunits is preserved thereby improving assay sensitivity and specificity. It is the same transfected antigens that are used in the Euroimmun indirect immunofluorescent assay.
- Day G, High S, Cot B, Tang-Wai D. Anti-NMDA-receptor encephalitis: case report and literature review of an under-recognised condition. J Gen Intern Med 2011: 1-6
- Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008;7: 327-40
- Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon RJ. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10: 63-74
- Moscato EH, Jain A, Peng X, Hughes EG, Dalmau J, Balice-Gordon RJ. Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory behaviour and cognition: insights from molecular cellular and synaptic studies. Eur J Neurosci 2010;32: 298-309
- Luca N, Daengsuwan T, Dalmau J, Jones K, deVeber G, Kobayashi J et al. Anti-N-methyl-D-aspartate receptor encephalitis: a newly recognised inflammatory brain disease in children. Arthritis Rheum 2011;63: 2516-22
- Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008; 7: 1091-8
- Barry H, Hardiman O, Healy DG, Keogan M, Moroney J, Molnar PP et al. Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis. Br J Psychol 2011;199: 508-9
- Gabilondo I, Saiz A, Galan L, Gonzalez V, Jadraque R, Sabater L et al. Analysis of relapses in anti-NMDAR encephalitis. Neurology 2011;77: 996-9
- Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominately non-paraneoplastic disorder of both sexes. Brain 2010; 133: 6-67
For further information contact the laboratory, (09) 307 4949 ext 22103 or:
Associate Professor Rohan Ameratunga , Immunopathologist: Locator 93-5724,
Dr Richard Steele , or The LabPLUS Immunology Team
Specimen Transport Instructions for Referring Laboratories
Send separated serum and CSF under standard cool pack refrigeration conditions.
Do not freeze