Summary Purpose To examine patterns of use, efficacy and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE). Methods Multicenter retrospective review of medical records and EEG reports in ten academic medical centers in North America and Europe, including 58 subjects, representing 60 episodes of RSE were identified between 1999 and 2012. Seven episodes occurred after anoxic brain injury. Key findings Permanent control of RSE was achieved in 57% (34/60) of episodes. Ketamine was felt to have contributed to permanent control (“possible” or “likely” responses) in 32% (19/60) including seven (12%) in which ketamine was the last drug added (likely responses). Four of the seven likely responses, but none of the 12 possible ones, occurred in patients with post-anoxic brain injury. No likely responses were observed when infusion rates were lower than 0.9mg/kg/h; when ketamine was introduced at least eight days after SE onset; or after failure of seven or more drugs. Ketamine was discontinued due to possible adverse events in five patients. Complications were mostly attributed to concurrent drugs, especially other anesthetics. Mortality rate was 43% (26/60), but was lower when SE was controlled within 24h of ketamine initiation (16% vs. 56%, p=0.0047). Significance Ketamine appears to be a relatively effective and safe drug for the treatment of RSE. This retrospective series provides preliminary data on effective dose and appropriate time of intervention to aid in the design of a prospective trial to further define the role of ketamine in the treatment of RSE.

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Importance: Histoplasmosis, a systemic mycosis caused by the fungus Histoplasma capsulatum, primarily affects immune-suppressed patients and commonly involves the lung and rarely the central nervous system (CNS). Herein, we report a case of isolated CNS histoplasmosis presenting with pontine stroke and meningitis. Observations: A 35-year-old, white, immunecompetent man was transferred from an outside facility with worsening dysarthria and confusion after having presented 4 weeks prior with dysarthria, gait ataxia, and bilateral upper extremity weakness. Brain magnetic resonance imaging revealed bilateral pontine strokes, and the working diagnosis was ischemic infarctions, presumed secondary to small vessel vasculitis. Cerebral spinal fluid (CSF) examination showed marked abnormalities including an elevated protein level (320 mg/dL), low glucose level (2 mg/dL), and high white blood cell count (330/ mm 3 ; 28% lymphocytes, 56% neutrophils, and 16% monocytes) suggestive of a bacterial, fungal, or tuberculosis meningitis. Empirical antibiotics and a second trial of intravenous steroids were started before infectious etiologies of meningitis were ultimately ruled out. Repeated magnetic resonance imaging of the brain revealed no evidence of new ischemic lesions. On hospital day 11, results of his CSF Histoplasma antigen and urine antigen tests were positive. His CSF culture also was positive for H capsulatum. The patient was treated initially with liposomal amphotericin B, 430 mg daily, but changed to voriconazole, 300 mg twice daily, secondary to renal insufficiency and eventually continued treatment with itraconazole cyclodextrin, 100 mg twice daily. Computed tomographic imaging revealed obstructive hydrocephalus, and a ventriculoperitoneal shunt was placed that successfully decompressed the ventricles. At 1 year, the patient demonstrated good clinical improvement and results of follow-up CSF cultures were negative. Conclusions and Relevance: While pulmonary involvement of histoplasmosis in immune-suppressed patients is common, systemic presentation of this fungal infection in immune-competent patients is rare and selflimiting. Isolated CNS histoplasmosis is exceedingly rare. Clinicians should consider CNS histoplasmosis in the differential diagnosis in atypical stroke cases, particularly those presenting with meningitis.

This case helps illustrate the utility of plasmapheresis in management of HIT when anticoagulation is contraindicated.

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