GABAA receptor autoimmunity after alemtuzumab treatment for multiple sclerosis.

A 68-year-old man with a 9-year history of relapsing-remitting multiple sclerosis previously treated with natalizumab and fingolimod achieved clinical and radiologic stability with alemtuzumab. Sixteen months after administration of the second cycle, he developed behavioral changes and focal seizures, characterized by aphasia and motor automatisms. Seizures were refractory to multiple antiepileptic drugs and evolved into epilepsia partialis continua and, after 1 week, into generalized status epilepticus (see timeline, [doi.org/10.5061/dryad.pvmcvdnht][1]). EEG showed bilateral temporal slowing and epileptiform discharges. Brain MRI revealed new large multifocal nonenhancing cortical/subcortical abnormalities involving bilaterally the frontal and temporal lobes (figure 1, A and B). Routine blood analyses were unremarkable, except for a reduced lymphocyte count (730/μL; B cells 50%, T cells 36%). CSF analysis showed pleocytosis (12 cells/μL) and increased proteins (53.8 mg/dL), whereas extensive screening for infections (including JC virus, herpes simplex virus 1-2-6, varicella-zoster virus, cytomegalovirus, Enterovirus , Listeria , Haemophilus , Cryptococcus , and bacterial and fungi cultures) yielded negative results. Fixed cell-based and Western Blot commercial assays (Euroimmun, Lubeck) excluded the presence of neuronal antibodies, including Hu, Yo, Ri, Tr, GAD65, CV2/CRMP5, Ma2, SOX1, amphiphysin, N-methyl-D-aspartate receptor, LGI1, CASPR2, AMPAR1/2, gamma-aminobutyric acid-B receptor, and dipeptidyl peptidase-like protein 6. Whole-body computed axial tomography did not show any malignancies. A right parietal brain biopsy showed unspecific gliosis without inflammatory infiltrates. [1]: https://doi.org/10.5061/dryad.pvmcvdnht