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

JAMA Neurol. 2016 Jun 1;73(6):706-13. doi: 10.1001/jamaneurol.2016.0232.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / complications*
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / diagnostic imaging
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / metabolism
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis / therapy
  • Antibodies / blood
  • Antibodies / cerebrospinal fluid
  • Atrophy / diagnostic imaging
  • Atrophy / etiology
  • Cerebellum / diagnostic imaging
  • Cerebellum / pathology*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Immunotherapy / methods
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurologic Examination
  • Receptors, N-Methyl-D-Aspartate / immunology
  • Retrospective Studies
  • Young Adult

Substances

  • Antibodies
  • Receptors, N-Methyl-D-Aspartate