The patient had multiple sclerosis while receiving ocrelizumab monotherapy. EXPOSURES Ocrelizumab monotherapy.RESULTS A 78-year-old man with progressive multiple sclerosis treated with ocrelizumab monotherapy for 2 years presented with 2 weeks of progressive visual disturbance and confusion. Examination demonstrated a right homonymous hemianopia, and magnetic resonance imaging revealed an enlarging nonenhancing left parietal lesion without mass effect. Cerebrospinal fluid revealed 1000 copies/mL of JC virus, confirming the diagnosis of PML. Blood work on diagnosis revealed grade 2 lymphopenia, with absolute lymphocyte count of 710/μL, CD4 of 294/μL (reference range, 325-1251/μL), CD8 of 85/μL (reference range, 90-775/μL), CD19 of 1/μL, preserved CD4/CD8 ratio (3.45), and negative HIV serology. Retrospective absolute lymphocyte count revealed intermittent grade 1 lymphopenia that preceded ocrelizumab (absolute lymphocyte count range, 800-1200/μL). The patient's symptoms progressed over weeks to involve bilateral visual loss, right-sided facial droop, and dysphasia. Ocrelizumab was discontinued and off-label pembrolizumab treatment was initiated. The patient nevertheless declined rapidly and ultimately died. PML was confirmed at autopsy. CONCLUSIONS AND RELEVANCEIn this case report, PML occurrence was likely a result of the immunomodulatory function of ocrelizumab as well as age-related immunosenescence. This case report emphasizes the importance of a thorough discussion of the risks and benefits of ocrelizumab, especially in patients at higher risk for infections such as elderly patients.

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Purpose of Review Public acceptance of Cannabis sativa L. (cannabis) as a therapeutic option grows despite lags in both research and clinician familiarity. Cannabis-whether as a medical, recreational, or illicit substance-is and has been commonly used by patients. With ongoing decriminalization efforts, decreased perception of harms, and increased use of cannabis in the treatment of symptoms and disease, it is critical for clinicians to understand the rationale for specific therapies and their medical and practical implications for patients. In view of the opioid crisis, overall patient dissatisfaction, and lack of adherence to current chronic pain and headache therapies, this review provides up-to-date knowledge on cannabis as a potential treatment option for headache pain. Recent Findings Research into the use of cannabinoids for disease treatment have led to FDA-approved drugs for seizures, nausea, and vomiting caused by cancer chemotherapy; and for decreased appetite and weight loss in people with HIV/AIDS. For a wide variety of conditions and symptoms (including chronic pain), cannabis has gained increasing acceptance in society. The effects of cannabidiol (CBD) and tetrahydrocannabinol (THC) in pain pathways have been significantly elucidated. An increasing number of retrospective studies have shown a decrease in pain scores after administration of cannabinoids, as well as longterm benefits such as reduced opiate use. Yet, there is no FDA-approved cannabis product for headache or other chronic pain disorders. More is being done to determine who is likely to benefit from cannabis as well as to understand the long-term effects and limitations of the treatment. Summary Cannabis can refer to a number of products derived from the plant Cannabis sativa L. Relatively well-tolerated, these products come in different configurations, types, and delivery forms. Specific formulations of the plant have been shown to be an effective treatment modality for chronic pain, including headache. It is important for clinicians to know which product is being discussed as well as the harms, benefits, contraindications, interactions, and unknowns in order to provide the best counsel for patients.This article is part of the Topical Collection on Hot Topics in Pain and Headache * Robert A. Duarte