Brainstem encephalitis: etiologies, treatment, and predictors of outcome

Abstract

Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non-HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997-April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6%) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50%). Fifteen patients (18.5%) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95% CI: 1.03-1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95% CI: 1.09-1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95% CI: 1.06-1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy.

Fig. 1

Imaging and histopathological findings in representative cases of brainstem encephalitis. a ADEM left and middle panels, MRI axial FLAIR sequences demonstrating multifocal hyperintensities in the brainstem and cerebellum. Right panels demonstrate macrophage infiltration (upper, hematoxylin and eosin), demyelination (middle, Luxol fast blue), and relative preservation of axons (lower, neurofilament staining). Scale bar 100 μm. b CLIPPERS left panel (MRI coronal T1 post gadolinium) demonstrates punctate and curvilinear enhancing lesions scattered throughout the brainstem. Middle panel (MRI axial T2) demonstrates scattered pontine hyperintensities. Right panels demonstrate marked perivascular and parenchymal inflammation (upper, hematoxylin and eosin) with prominent lymphocytic infiltration (lower, CD3 staining). Macrophages were also present (not shown). Scale bar 100 μm. c Neurosarcoidosis left panels (MRI T2 and T1 post gadolinium) demonstrate an enhancing lesion in the right midbrain. Right panels (hematoxylin and eosin) demonstrate several non-caseating granulomas. Acid fast bacilli and silver staining did not demonstrate any organisms (not shown). Scale bar 100 μm