Original Investigation
June 2016

Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Author Affiliations
  • 1Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan
  • 2Department of Neurology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan
  • 3Department of Neurology, School of Medicine, St Marianna University, Kawasaki, Japan
  • 4Institut d’Investigacións Biomèdicques August Pi i Sunyer, Barcelona, Spain
  • 5Department of Neurology, University of Pennsylvania, Philadelphia
  • 6Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Neurol. 2016;73(6):706-713. doi:10.1001/jamaneurol.2016.0232

Importance  Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder that occurs with IgG antibodies against the GluN1 subunit of NMDAR. Some patients develop reversible diffuse cerebral atrophy (DCA), but the long-term clinical significance of progressive brain and cerebellar atrophy is unknown.

Objective  To report the long-term clinical implications of DCA and cerebellar atrophy in anti-NMDAR encephalitis.

Design, Setting, and Participants  A retrospective observational study and long-term imaging investigation was conducted in the Department of Neurology at Kitasato University. Fifteen patients with anti-NMDAR encephalitis admitted to Kitasato University Hospital between January 1, 1999, and December 31, 2014, were included; data analysis was conducted between July 15, 2015, and January 18, 2016.

Exposures  Neurologic examination, immunotherapy, and magnetic resonance imaging (MRI) studies were performed.

Main Outcomes and Measures  Long-term MRI changes in association with disease severity, serious complications (eg, pulmonary embolism, septic shock, and rhabdomyolysis), treatment, and outcome.

Results  The clinical outcome of 15 patients (median age, 21 years, [range, 14-46 years]; 10 [67%] female) was evaluated after a median follow-up of 68 months (range, 10-179 months). Thirteen patients (87%) received first-line immunotherapy (intravenous high-dose methylprednisolone, intravenous immunoglobulin, and plasma exchange alone or combined), and 4 individuals (27%) also received cyclophosphamide; 2 patients (13%) did not receive immunotherapy. In 5 patients (33%), ovarian teratoma was found and removed. Serious complications developed in 4 patients (27%). Follow-up MRI revealed DCA in 5 patients (33%) that, in 2 individuals (13%), was associated with progressive cerebellar atrophy. Long-term outcome was good in 13 patients (87%) and poor in the other 2 individuals (13%). Although cerebellar atrophy was associated with poor long-term outcome (2 of 2 vs 0 of 13 patients; P = .01), other features, such as DCA without cerebellar atrophy, serious complications, ventilatory support, or prolonged hospitalization, were not associated with a poor outcome. Five patients with DCA had longer hospitalizations (11.1 vs 2.4 months; P = .002), required ventilatory support more frequently (5 of 5 vs 4 of 10 patients; P = .04), and developed more serious complications (4 of 5 vs 0 of 10 patients; P = .004) compared with those without DCA. Although DCA was reversible, cerebellar atrophy was irreversible.

Conclusions and Relevance  In anti-NMDAR encephalitis, DCA can be reversible and does not imply a poor clinical outcome. In contrast, cerebellar atrophy was irreversible and associated with a poor outcome. This observation deserves further study to confirm progressive cerebellar atrophy as a prognostic marker of poor outcome.