PracticeUpdate Neurology June 2019

EDITOR’S PICKS 13

Treatment Approach to NREM Parasomnias Sleep Medicine Take-home message • Non-REM parasomnias, including sleepwalking and sleep terrors, are not uncommon complaints in the general population, and yet there are no large studies addressing optimal management. The authors of this study retrospectively identified 512 adult patients from their sleep laboratory database with videoPSG data who were treated for NREM parasomnias over 7.5 years with a median of 8 months of follow-up time. Their clinic’s approach is to use nonpharmacologic strategies as a first-line treatment and to discontinue any medications possibly contributing to the parasomnia. They found that these first- line strategies resulted in acceptable symptom control or resolution in 32% of patients, and 60% of patients were treated with medication, regardless of parasomnia type. The most common medication used was clonazepam (40%), and 72% of those treated with clonazepam had a good response. A total of 19% received antidepressants, most commonly fluoxetine, and 37% responded well. Fewer patients received z-drugs or sustained-release melatonin, but with generally good results, suggesting that zopiclone and melatonin may also be considered in the treatment of these patients. • This large study has helpful implications for those neurologists and sleep specialists who manage NREM parasomnias. Sarah Matteson Kranick MD Abstract BACKGROUND Non-REM parasomnias are not uncommon conditions in the general population. Current treatment options are based on small case series and reports. In this study, we aimed to present the clinical experience from a large cohort of patients. PATIENTS Five hundred and twelve patients with Non-REM parasomnia or parasom- nia overlap disorder (POD), who had undergone a video polysomnography and were exposed to treatment, were retrospectively identified. Treatment outcome was assessed based on patients’ reports, and treatment approach on a locally accepted hierarchy of interventions. RESULTS Forty percent of patients were diagnosed with sleepwalking, 23.8% with mixed-phenotype and 10% with POD. Ultimately, 97.2% reported adequate control of their symptoms. Moreover, 60.1% were treated with pharmacotherapy and 32.0% without, consistent across all phenotypes (p = 0.09). Benzodiazepines were the most common drugs prescribed (47.1%, p < 0.05). In the end, 37.7% of our patients were receiving a benzodiazepine as part of their successful treatment, 11.7% an antidepressant, 9.2% a z-drug, and 10.7% melatonin. Finally, 13.2%, 12.1%, and 5.8% of our patients reported good control of their symptoms with sleep hygiene, man- agement of sleep-disordered breathing, and psychological interventions (cognitive behavioral therapy [CBT] or mindfulness-based stress reduction [MBSR]), as mon- otherapy, respectively. CONCLUSION The treatment approach to effective treatment of the patients with Non-REM parasomnias or POD offering first sleep hygiene advice, next treatment of concurrent sleep disorders and management of other priming factors like stress and anxiety, and lastly pharmacotherapy for Non-REM parasomnia is supported by our results. Non pharmacological interventions were effective in one third of our patients, and CBT/MBSR and melatonin appeared promising new treatments. NREM Parasomnias: A Treatment Approach Based Upon a Retrospective Case Series of 512 Patients. Sleep Med 2019 Jan 01;53(xx)181-188, P Drakatos, L Marples, R Muza, et al. www.practiceupdate.com/c/79703

Pembrolizumab Treatment for

Progressive Multifocal Leukoencephalopathy The New England Journal of Medicine Take-home message • A cohort of 8 patients with progressive multi- focal leukoencephalopathy (PML) received one to three doses of pembrolizumab. In all patients, pembrolizumab induced down-regulation of PD-1 expression on lymphocytes both in the blood and the cerebrospinal fluid (CSF). Clinical improvement was observed in 5 patients, with an accompanying reduction in the JC viral load in the CSF and an increase in CD4+ and CD8+ anti–JC virus activity. No change in viral load or antiviral cellular immune response was seen in the remaining 3 patients. • Pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus in select patients with PML. Further research is warranted to evaluate the use of PD-1 inhibitors in the treatment of PML. Abstract BACKGROUND Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored. Programmed cell death protein 1 (PD-1) is a nega- tive regulator of the immune response that may contribute to impaired viral clearance. Whether PD-1 blockade with pembrolizumab could reinvigorate anti–JC virus immune activity in patients with PML was unknown. METHODS We administered pembrolizumab at a dose of 2 mg per kilogram of body weight every 4 to 6 weeks to eight adults with PML, each with a different underlying predispos- ing condition. Each patient received at least one dose but no more than three doses. RESULTS Pembrolizumab induced down-regulation of PD-1 expression on lymphocytes in peripheral blood and in cer- ebrospinal fluid (CSF) in all eight patients. Five patients had clinical improvement or stabilization of PML accompanied by a reduction in the JC viral load in the CSF and an increase in in vitro CD4+ and CD8+ anti–JC virus activity. In the other three patients, no meaningful change was observed in the viral load or in the magnitude of antiviral cellular immune response, and there was no clinical improvement. CONCLUSIONS Our findings are consistent with the hypothe- sis that in some patients with PML, pembrolizumab reduces JC viral load and increases CD4+ and CD8+ activity against the JC virus; clinical improvement or stabilization occurred in five of the eight patients who received pembrolizumab. Further study of immune checkpoint inhibitors in the treat- ment of PML is warranted. Pembrolizumab Treatment for Progressive Multifocal Leu- koencephalopathy. N Engl J Med 2019 Apr 10;[EPub Ahead of Print], I Cortese, P Muranski, Y Enose-Akahata, et al. www.practiceupdate.com/c/82180

VOL. 4 • NO. 2 • 2019