Faculty Bibliography

New-onset refractory status epilepticus (NORSE) is defined as a state of persistent seizures with no identifiable etiology in patients without preexisting epilepsy that lasts longer than 24h despite optimal therapy. Management of NORSE is challenging, and the role of immunotherapy (IT) is unclear. We identified patients fulfilling the criteria for NORSE at a single institution. These patients were described, analyzed, and compared with NORSE cases available from the literature. Finally, a pooled analysis of available case series was conducted to compare the outcomes in patients who received IT with those not treated with IT during the course of NORSE in order to generate hypotheses for further research. In our case series, NORSE was diagnosed in 11 patients (9 females) with a mean age of 48 years and a mean duration of 54.4 days. Autoantibodies were identified in 7 patients, of which anti-GAD (glutamic acid decarboxylase) and anti-NMDAR (N-methyl-D-aspartate receptor) were most frequent. Of the 11 patients, 8 were treated with IT (intravenous steroids, immunoglobulins, plasmapheresis, or a combination), and 4 received chemotherapy. Of the 8 patients treated with IT, 6 had favorable outcomes (defined as any outcome other than death, vegetative state, or inability to take care of oneself) compared with 0 out of 3 patients who did not receive IT. Difference in outcomes was significant (p=0.026). Pooled analysis of all identified case series, including ours, showed a statistically significant effect (p=0.022), with favorable outcomes in 42% of the patients who received any IT compared with 20% in those who did not. In all patients with refractory SE and negative comprehensive investigations, a diagnosis of NORSE should be considered. This would aid planning for early immunotherapy. Currently, only Class IV evidence for the use of immunotherapy in NORSE is available. Prospective multicenter studies are necessary to assess the true efficacy of IT in NORSE.

Bevacizumab is widely used for treatment of high-grade gliomas and other malignancies. Because bevacizumab has been shown to be associated with neurocognitive decline, this study is designed to investigate whether prolonged treatment with bevacizumab is also associated with brain atrophy. We identified 12 high-grade glioma patients who received bevacizumab for 12 months at the first recurrence and 13 matched controls and blindly compared the volumes of the contralateral hemispheres and contralateral ventricle in these two groups at baseline and after 12 ± 2 months of the baseline scan by two independent analyses. The volumes of the contralateral hemispheres and ventricles did not differ significantly between the two groups at baseline. Whereas, in the control group the volumes of the contralateral hemisphere changed subtly from baseline to follow-up (p = 0.23), in the bevacizumab-treated group the volumes significantly decreased from baseline to follow-up (p = 0.03). There was significant increase in the contralateral ventricle volume from base line to follow-up scans in both the control group (p = 0.01) and in the bevacizumab group (p = 0.005). Both the absolute and the percentage changes of contralateral hemisphere volumes and contralateral ventricular volumes between the two patient groups were statistically significant (p < 0.05). Results of this study demonstrate prolonged treatment with bevacizumab is associated with atrophy of the contralateral brain hemisphere.