Progressive Cerebellar Atrophy and Anti-NMDA Receptor Encephalitis

A retrospective observation study of 15 patients ( median age 21yrs) with Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis suggests that while the diffuse cerebral atrophy can be reversible the cerebellar atrophy is irreversible and associated with a poor clinical outcome.

In an accompanying editorial Dr Maarten J. Titulaer writes that progressive cerebellar atrophy is a potential biomarker for less favorable response in patients with anti-NMDAR encephalitis, especially in those admitted to the ICU. In addition, the development of diffuse cerebral atrophy should not be a reason to withhold treatment in patients with anti-NMDAR encephalitis. Overall, the outcome is good for most patients, despite long disease duration or the need for mechanical ventilation.

However, it is of upmost importance to try to limit the time of ICU admission, since half of those patients developed 1 or more serious complication, and any of these complications could add to irreversible disabilities. Physicians will agree that prompt treatment is warranted in all patients, and the use of aggressive immunotherapy is advocated if initial therapy does not lead to a quick start of improvement,3 especially for patients in the ICU.

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.