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Autoimmune encephalitis screen-a review of rapid diagnostic screening in 600 patients over 5 years.
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J Neurol Neurosurg Psychiatry 2013 Nov; 84(11):e2
Authors: Girija Sadalage, Abid Karim, Saiju Jacob
Queen Elizabeth Neuroscience Centre, University Hospitals of Birmingham; University of Birmingham.
Autoimmune encephalitis is characterised by encephalopathy, seizures, memory disturbance and neuro-psychiatric symptoms. One of the initial antibodies described were those against the voltage gated potassium channel (VGKC),(1) which causes limbic encephalitis (LE) often associated with hypontaremia. Later antibodies against N-methyl D-aspartate receptors (NMDAR) were found associated with ovarian teratoma,(2) with a prominent neuropsychiatric onset and later developing involuntary movements, autonomic disturbance and respiratory difficulties. NMDAR LE is now known to occur mainly in a non-paraneoplastic setting. Antibodies have also been described against other glutamate receptors (AMPAR1, AMPAR2 etc) and also against GABAb receptors. The original assay for VGKC was done using radioimmunoprecipitation, but it was proven that the antibodies are directed against complexing proteins attached to VGKC, rather than VGKC itself. Immunocytofluorescent techniques have been devised which will test for specific antibodies against LGI1, Caspr2 etc. Recently, an immunofluorescence chip has been prepared by the Euroimmun laboratories which utilises the same principle, but can be used as a screening tool for six different antibodies (LGI1, Caspr2, NMDAR, AMPAR1, AMPAR2 and GABAb) at the same time. The sensitivity for different antibodies is slightly variable but is useful for quick screening and has a very rapid turnaround time in our laboratory (less than a week). We analysed nationwide samples sent to our laboratory over the last 5 years and consecutively looked at 600 samples tested during this period. NMDAR antibodies were the most commonly found seen in 3% of samples (18/600). The broader screen was performed in 413 patients which identified 6 patients with LGI1 antibodies (1.5%) and 1 with GABAb antibody. Weakly positive AMPAR2 antibodies, Caspr2 and LGI1 antibodies were seen in one patient each. Details of the assay and clinical data from representative patients would be presented. Results of patients having non-LGI1, non-Caspr2 antibodies using the more sensitive assay for VGKC would also be discussed. The most commonly found antibodies when screening for autoimmune encephalitis are directed against NMDAR, using the new multi-antibody assay. This is similar to the big encephalitis screen studies from California(3) and other similar labs. However, the current study looks at an unselected cohort of patients referred from all specialties and across the country, with varying clinical presentations. The rapid turnover of the assay aids the clinicians in commencing appropriate therapy at the earliest opportunity, thereby minimizing long-term sequelae. However, the assay may not be sensitive enough to pick up low-titre antibodies and when the clinical suspicion is high, more sensitive confirmatory tests may be required (eg: radioimmunoprecipitation). The increasing spectrum of autoimmune encephalitis and the screening for a wider array of antibodies have revealed more patients with "seronegative" LE who need to be studied in more detail to identify their potential immunological targets.
PMID: 24109018 [PubMed - as supplied by publisher]