PMID- 27111481 OWN - NLM STAT- MEDLINE DCOM- 20170525 LR - 20181113 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 73 IP - 6 DP - 2016 Jun 1 TI - Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis. PG - 706-13 LID - 10.1001/jamaneurol.2016.0232 [doi] AB - 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. FAU - Iizuka, Takahiro AU - Iizuka T AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Kaneko, Juntaro AU - Kaneko J AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Tominaga, Naomi AU - Tominaga N AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Someko, Hidehiro AU - Someko H AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Nakamura, Masaaki AU - Nakamura M AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Ishima, Daisuke AU - Ishima D AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Kitamura, Eiji AU - Kitamura E AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Masuda, Ray AU - Masuda R AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Oguni, Eiichi AU - Oguni E AD - Department of Neurology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan. FAU - Yanagisawa, Toshiyuki AU - Yanagisawa T AD - Department of Neurology, School of Medicine, St Marianna University, Kawasaki, Japan. FAU - Kanazawa, Naomi AU - Kanazawa N AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. FAU - Dalmau, Josep AU - Dalmau J AD - Institut d'Investigacions Biomedicques August Pi i Sunyer, Barcelona, Spain5Department of Neurology, University of Pennsylvania, Philadelphia6Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Spain. FAU - Nishiyama, Kazutoshi AU - Nishiyama K AD - Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan. LA - eng GR - R01 NS077851/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Antibodies) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM CIN - JAMA Neurol. 2016 Jun 1;73(6):643-4. PMID: 27110872 MH - Adolescent MH - Adult MH - Anti-N-Methyl-D-Aspartate Receptor Encephalitis/*complications/diagnostic imaging/metabolism/therapy MH - Antibodies/blood/cerebrospinal fluid MH - Atrophy/diagnostic imaging/etiology MH - Cerebellum/diagnostic imaging/*pathology MH - Female MH - Humans MH - Image Processing, Computer-Assisted MH - Immunotherapy/methods MH - Longitudinal Studies MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Neurologic Examination MH - Receptors, N-Methyl-D-Aspartate/immunology MH - Retrospective Studies MH - Young Adult PMC - PMC5018902 MID - NIHMS814779 COIS- Disclosures: Dr Dalmau reported receiving royalties from Athena Diagnostics for a patent for the use of Ma2 as an autoantibody test and licensing fees from Euroimmun for a patent for the use of N-methyl-d-aspartate and gamma-aminobutyric acid-B receptor (as autoantibody tests). EDAT- 2016/04/26 06:00 MHDA- 2017/05/26 06:00 PMCR- 2017/06/01 CRDT- 2016/04/26 06:00 PHST- 2016/04/26 06:00 [entrez] PHST- 2016/04/26 06:00 [pubmed] PHST- 2017/05/26 06:00 [medline] PHST- 2017/06/01 00:00 [pmc-release] AID - 2516856 [pii] AID - 10.1001/jamaneurol.2016.0232 [doi] PST - ppublish SO - JAMA Neurol. 2016 Jun 1;73(6):706-13. doi: 10.1001/jamaneurol.2016.0232.