Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-<i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Encephalitis
Authors: Takahiro Iizuka, Juntaro Kaneko, Naomi Tominaga, Hidehiro Someko, Masaaki Nakamura, Daisuke Ishima, Eiji Kitamura, Ray Masuda, Eiichi Oguni, Toshiyuki Yanagisawa, Naomi Kanazawa, Josep Dalmau, Kazutoshi Nishiyama
Journal: JAMA Neurology (2016)

<h3>Importance</h3> Anti-<i>N</i>-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. <h3>Objective</h3> To report the long-term clinical implications of DCA and cerebellar atrophy in anti-NMDAR encephalitis. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> Neurologic examination, immunotherapy, and magnetic resonance imaging (MRI) studies were performed. <h3>Main Outcomes and Measures</h3> Long-term MRI changes in association with disease severity, serious complications (eg, pulmonary embolism, septic shock, and rhabdomyolysis), treatment, and outcome. <h3>Results</h3> 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;<i>P</i> = .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;<i>P</i> = .002), required ventilatory support more frequently (5 of 5 vs 4 of 10 patients;<i>P</i> = .04), and developed more serious complications (4 of 5 vs 0 of 10 patients;<i>P</i> = .004) compared with those without DCA. Although DCA was reversible, cerebellar atrophy was irreversible. <h3>Conclusions and Relevance</h3> 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.