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



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



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.



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



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



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.



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.
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Takahiro
T
Iizuka
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Juntaro
J
Kaneko
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Naomi
N
Tominaga
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Hidehiro
H
Someko
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Masaaki
M
Nakamura
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Daisuke
D
Ishima
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Eiji
E
Kitamura
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Ray
R
Masuda
Department of Neurology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan.
Eiichi
E
Oguni
Department of Neurology, School of Medicine, St Marianna University, Kawasaki, Japan.
Toshiyuki
T
Yanagisawa
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Naomi
N
Kanazawa
Institut d'Investigacións Biomèdicques August Pi i Sunyer, Barcelona, Spain5Department of Neurology, University of Pennsylvania, Philadelphia6Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
Josep
J
Dalmau
Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.
Kazutoshi
K
Nishiyama
D000293:Adolescent; D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D000906:Antibodies / Q000097:blood / Q000134:cerebrospinal fluid; D001284:Atrophy / Q000000981:diagnostic imaging / Q000209:etiology; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007167:Immunotherapy / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D012189:Retrospective Studies; D055815:Young Adult
D000906:Antibodies; D016194:Receptors, N-Methyl-D-Aspartate