Sleepiness in neurological disorders.

Sleepiness is a frequent and underrecognized symptom in neurological disorders, that impacts functional outcomes and quality of life. Multiple and potentially additive factors might contribute to sleepiness in neurological disorders, including sleep quality alterations, circadian rhythm disorders, drugs, and sleep disorders including sleep apnea or central disorders of hypersomnolence. Physician awareness of the possible symptoms of hypersomnolence, and associated causes is of crucial importance to allow proper identification and treatment of underlying causes. This review first provides a brief overview on clinical aspects of excessive daytime sleepiness, and diagnosis tools, then examines its frequency and mechanisms in various neurological disorders, including neurodegenerative disorders, multiple sclerosis, autoimmune encephalitis, epilepsy, and stroke.

Biotherapies in multiple sclerosis: a step toward remyelination and neuroprotection?

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS), characterized by CNS-restricted inflammation with subsequent demyelination and neurodegeneration. Current disease-modifying therapies efficiently reduce relapse rate and new lesions appearance, but still fail to impact the progressive course of the disease. There is a great need for the avenue of new therapies aimed at promoting myelin repair or reducing neurodegeneration that should result in the prevention of neurological disability in this chronic disease. This review will focus on the potentials and limitations of biotherapies that are currently developed for the promotion of CNS repair in MS, either monoclonal antibodies targeting axonal growth and remyelination, or cell therapies aimed at replacing the depleted myelinating cells within the CNS. As other researches aimed at promoting neuroprotection or remyelination are following a classical pharmacological approach, they will not be described in this review, which will focus on antibody-based therapies and cell therapies.

Steroid-sparing effects of angiotensin-II inhibitors in glioblastoma patients.

BACKGROUND: The standard of care in patients with glioblastoma (GBM) relies on surgical resection, radiation therapy (RT), and temozolomide. Steroids are required in almost all patients to reduce peritumoral edema, but are associated with numerous side effects. Vascular endothelial growth factor (VEGF) is a key driver of peritumoral edema and angiogenesis in human GBM. Recently, angiotensin-II inhibitors were reported to reduce VEGF secretion and tumor growth in some animal models. METHODS: To investigate whether angiotensin-II inhibitors might have a similar effect in humans and before undertaking a prospective study, we retrospectively investigated a series of 87 consecutive, newly diagnosed GBM patients, treated in a single center. Amongst these patients, 29 (33%) were already treated before RT for high blood pressure (HBP), 18 of them (21%) with an angiotensin-II inhibitor. In all patients, performance status, surgical procedures, and steroid dosages were documented. RESULTS: Patients treated with angiotensin-II inhibitors, but not other antihypertensive drugs, required half of the steroids of the other patients during radiotherapy (P = 0.005 in multivariate analysis, considering other antihypertensive treatments, surgical resection, and performance status). This effect of angiotensin-II inhibitors was also significant at the beginning of radiotherapy (P = 0.03 in multivariate analysis). Treatment with angiotensin-II inhibitors had no effect on survival (16.2 vs. 17.9 months for the treated and the non-treated group, respectively, P = 0.77). CONCLUSION: Angiotensin-II inhibitors might display significant steroid-sparing effects in brain tumor patients. Given the morbidity associated with steroids, this finding might have important practical consequences in these patients and warrants a randomized study.