Gloria von Geldern

Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project.

Brentuximab vedotin (BV) is an anti‐CD30 monoclonal antibody‐drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus‐induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. In the current study, the authors reported 5 patients who developed BV‐associated PML, including 2 immunocompetent patients.

HIV-associated opportunistic infections of the CNS

Survival in people infected with HIV has improved because of an increasingly powerful array of antiretroviral treatments, but neurological symptoms due to comorbid conditions, including infection with hepatitis C virus, malnutrition, and the effects of accelerated cardiovascular disease and ageing, are increasingly salient. A therapeutic gap seems to exist between the salutary effects of antiretroviral regimens and the normalisation of neurological function in HIV-associated neurocognitive disorders. Despite the advances in antiretroviral therapy, CNS opportunistic infections remain a serious burden worldwide. Most opportunistic infections can be recognised by a combination of characteristic clinical and radiological features and are treatable, but some important challenges remain in the diagnosis and management of HIV-associated opportunistic infections.

The influence of nutritional factors on the prognosis of multiple sclerosis

The effect of nutrition and dietary supplements on the course of multiple sclerosis (MS) is a topic of great interest to both patients and clinicians. In particular, vitamin D status has been shown to influence both the incidence and the course of MS. High vitamin D levels are probably protective against the development of MS, although the efficacy of vitamin D supplementation in slowing progression of MS remains to be established. The influence of polyunsaturated fatty acids (PUFAs) on the development and course of MS has also long been under investigation. Small clinical trials suggest a modest reduction in the severity and duration of relapses in patients with MS receiving PUFA supplements. Other nutritional factors have been evaluated for their effect on MS disease progression, including milk proteins, gluten, probiotics, antioxidants (uric acid, vitamins A, C and E, lipoic acid), polyphenols, Ginkgo biloba extracts and curcumin. However, further studies are needed to evaluate the effects of these dietary components on the relapse rate and progression of MS. This Review gives an overview of the literature on the nutritional factors most commonly implicated as having an effect on MS and discusses the biological rationale that is thought to underlie their influence.

PML-IRIS in a patient treated with brentuximab

A 38-year-old woman was diagnosed with cutaneous anaplastic T-cell lymphoma that proved refractory to methotrexate, bexarotene, denileukin diftitox, interferon γ-1b, interferon α-2b, vorinostat, and pralatrexate. She was therefore started on the newly approved monoclonal anti-CD30 antibody brentuximab vedotin. Treatment with brentuximab 1.8 mg/kg IV every 3 weeks quickly led to disappearance of her cutaneous tumors. The day after her second brentuximab infusion she developed word-finding difficulties and unsteady gait. Due to further neurologic deterioration, she was admitted to an outside hospital. Brain MRI revealed multifocal enhancing white matter lesions throughout bilateral cerebral hemispheres and posterior fossa (figure, A–C). Brain biopsy was performed 15 days after her last brentuximab dose to rule out metastases and she was diagnosed with progressive multifocal leukoencephalopathy (PML) (figure, J). The patient was discharged home with hospice care. Upon discharge, she was started on prednisone 50 mg daily to help treat her eczema. Her family brought her to our clinic for a second opinion.

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

This chapter will review the spectrum of immune-mediated diseases that affect the nervous system and may result in an admission to the neurological intensive care unit. Immunomodulatory strategies to treat acute exacerbations of neurological diseases caused by aberrant immune responses are discussed, but strategies for long-term immunosuppression are not presented. The recommendations for therapeutic intervention are based on a synthesis of the literature, and include recommendations by the Cochrane Collaborative, the American Academy of Neurology, and other key organizations. References from recent publications are provided for the disorders and therapies in which randomized clinical trials and large evidenced-based reviews do not exist. The chapter concludes with a brief review of the mechanisms of action, dosing, and side effects of commonly used immunosuppressive strategies in the neurocritical care unit.

Impact of Multiple Sclerosis Project ECHO on Provider Confidence and Clinical Practice

Background Project ECHO (Extension for Community Healthcare Outcomes) represents a novel approach to addressing disparities in multiple sclerosis (MS) care. A primary mechanism of the program is the use of case consultations to rapidly transfer knowledge from content experts to community providers who care for individuals with MS. Methods MS Project ECHO was pilot tested as a weekly 60-minute videoconference delivered to 24 clinicians across 13 practice sites over 41 weeks. Participants completed a variety of measures related to their experience in the program and answered qualitative questions via exit interview. We report on the responses to exit interview questions related to the case consultation component of MS Project ECHO. Results Participant responses regarding case consultations generated four themes: 1) improved confidence among participants in the existing treatment decision, 2) direct change in the care of the patient provided by the participant, 3) changed practice habits for all of the participants patients with MS, and 4) increased perception that patients had confidence in the participant as an MS care provider. Conclusions Participant responses support MS Project ECHO as a program that may directly and indirectly affect the way providers deliver MS care in underserved areas. Further research is needed to examine the resulting effect on patient outcomes.