A complex and severe encephalitis associated with four co-existing neuronal cell-surface autoantibodies

Michael Gilligan; Luke O'Donnell; Andrew Westbrook; Niall Tubridy; Sean 'o Riordan; Christopher McGuigan; Sean Connolly; Michael Farrell; Patrick Waters; Sarosh R Irani; Justin A Kinsella

doi:10.1016/j.jneuroim.2024.578501

A complex and severe encephalitis associated with four co-existing neuronal cell-surface autoantibodies

J Neuroimmunol. 2024 Dec 3:399:578501. doi: 10.1016/j.jneuroim.2024.578501. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland; Department of Clinical Neurophysiology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
² Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
³ Department of Anaesthesia, Intensive Care, and Pain medicine, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
⁴ Department of Clinical Neurophysiology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
⁵ Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
⁶ Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Department of clinical Neurology, John Radcliffe Hospital, Oxford, UK.
⁷ Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland. Electronic address: justinkinsella@svhg.ie.

PMID: 39647404
DOI: 10.1016/j.jneuroim.2024.578501

Abstract

Many forms of autoimmune encephalitis are mediated by neuronal cell-surface directed autoantibodies. The co-occurrence of four neuronal cell-surface antibodies in a single patient is exceptionally rare. We report a patient who had a severe encephalitis associated with antibodies to NMDA, Glycine, GABA_A and GABA_B receptors. Case: A 28-year-old man on tacrolimus presented with a first seizure. Thereafter, he developed confusion, cerebellar signs, opsoclonus, neuromyotonia and medication-refractory seizures. CSF sampling revealed 826 white cells and NMDA, glycine and GABA_B receptor antibodies: all were also detected in serum along with additional GABA_A receptor antibodies. Neural antibodies were detected using fixed (NMDA, GABA_A, GABA_B receptor) or live (glycine receptor) cell-based assays at Oxford Neuroimmunology Laboratory, Oxford, UK. MRI brain demonstrated cerebellar leptomeningeal enhancement and a hyperintense lesion in the cerebellar vermis. EEG revealed extreme delta brush and needle EMG confirmed neuromyotonia. No underlying malignancy was detected. Methylprednisolone, IVIG, Rituximab, therapeutic plasma exchange, cyclophosphamide and bortezomib were administered sequentially, with minimal clinical improvement. Death secondary to respiratory sepsis occurred on the 714th hospital day. Postmortem revealed pan-cerebellar atrophy with Purkinje cell loss; dentate nucleus ganglionopathy, and thoracolumbar cord myelopathy. In summary, the detection of multiple neuronal cell-surface antibodies in autoimmune encephalitis is unusual and may result in a complex overlap syndrome with a poor response to immunotherapy.

Keywords: Antibody; Autoimmune; Encephalitis; Neuroinflammation.