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Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis.
JAMA Neurol. 2016 06 01; 73(6):706-13.JN

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.

Authors+Show Affiliations

Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Department of Neurology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan.Department of Neurology, School of Medicine, St Marianna University, Kawasaki, Japan.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.Institut d'Investigacións Biomèdicques August Pi i Sunyer, Barcelona, Spain5Department of Neurology, University of Pennsylvania, Philadelphia6Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.Department of Neurology, School of Medicine, Kitasato University, Sagamihara, Japan.

Pub Type(s)

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

Language

eng

PubMed ID

27111481

Citation

Iizuka, Takahiro, et al. "Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis." JAMA Neurology, vol. 73, no. 6, 2016, pp. 706-13.
Iizuka T, Kaneko J, Tominaga N, et al. Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis. JAMA Neurol. 2016;73(6):706-13.
Iizuka, T., Kaneko, J., Tominaga, N., Someko, H., Nakamura, M., Ishima, D., Kitamura, E., Masuda, R., Oguni, E., Yanagisawa, T., Kanazawa, N., Dalmau, J., & Nishiyama, K. (2016). Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis. JAMA Neurology, 73(6), 706-13. https://doi.org/10.1001/jamaneurol.2016.0232
Iizuka T, et al. Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis. JAMA Neurol. 2016 06 1;73(6):706-13. PubMed PMID: 27111481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Progressive Cerebellar Atrophy With Long-term Outcome in Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis. AU - Iizuka,Takahiro, AU - Kaneko,Juntaro, AU - Tominaga,Naomi, AU - Someko,Hidehiro, AU - Nakamura,Masaaki, AU - Ishima,Daisuke, AU - Kitamura,Eiji, AU - Masuda,Ray, AU - Oguni,Eiichi, AU - Yanagisawa,Toshiyuki, AU - Kanazawa,Naomi, AU - Dalmau,Josep, AU - Nishiyama,Kazutoshi, PY - 2016/4/26/entrez PY - 2016/4/26/pubmed PY - 2017/5/26/medline SP - 706 EP - 13 JF - JAMA neurology JO - JAMA Neurol VL - 73 IS - 6 N2 - 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. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/27111481/Association_of_Progressive_Cerebellar_Atrophy_With_Long_term_Outcome_in_Patients_With_Anti_N_Methyl_d_Aspartate_Receptor_Encephalitis_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2016.0232 DB - PRIME DP - Unbound Medicine ER -