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CNS Drugs

Stefanie Kuerten, Leila J Jackson, Joel Kaye, Timothy L Vollmer
Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells...
October 12, 2018: CNS Drugs
Marcelo E Bigal, Alan M Rapoport, Stephen D Silberstein, Sarah Walter, Richard J Hargreaves, Ernesto Aycardi
Calcitonin gene-related peptide (CGRP) is a neuropeptide of importance in migraine pathogenesis. Its central role in migraine was proven pharmacologically by the development of CGRP receptor antagonists. Monoclonal antibodies targeting CGRP or its receptor are effective in the preventive treatment of episodic and chronic migraine and are considered potential breakthroughs in their treatment. Fremanezumab (previously known as TEV-48125, LBR-101, or RN-307) is a humanized IgG2a monoclonal antibody that binds to CGRP...
October 11, 2018: CNS Drugs
Arjun Tarakad, Joohi Jimenez-Shahed
The basal ganglia and dopaminergic pathways play a central role in hyperkinetic movement disorders. Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disorders, but have recently gained more attention following their development for specific indications in the United States. At present, there are three commercially available VMAT2 inhibitors: tetrabenazine, deutetrabenazine, and valbenazine...
October 10, 2018: CNS Drugs
Alexander Klistorner, Yi Chai, Letizia Leocani, Philipp Albrecht, Orhan Aktas, Helmut Butzkueven, Tjalf Ziemssen, Focke Ziemssen, Jette Frederiksen, Lei Xu, Diego Cadavid
BACKGROUND: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies. OBJECTIVE: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants...
September 28, 2018: CNS Drugs
Kevin P Jensen, Elise E DeVito, Sarah Yip, Kathleen M Carroll, Mehmet Sofuoglu
Opioid overdoses recently became the leading cause of accidental death in the US, marking an increase in the severity of the opioid use disorder (OUD) epidemic that is impacting global health. Current treatment protocols for OUD are limited to opioid medications, including methadone, buprenorphine, and naltrexone. While these medications are effective in many cases, new treatments are required to more effectively address the rising societal and interpersonal costs associated with OUD. In this article, we review the opioid and cholinergic systems, and examine the potential of acetylcholine (ACh) as a treatment target for OUD...
September 26, 2018: CNS Drugs
Mark Gudesblatt, Karl Wissemann, Myassar Zarif, Barbara Bumstead, Lori Fafard, Jeffrey Wilken, Karen Blitz, Marijean Buhse, Sourav Santra, Christophe Hotermans, Lily Lee
An Online First version of this article was made available online at on 24 August 2018. An error was subsequently identified in the article, and the following correction should be noted.
September 22, 2018: CNS Drugs
Pierre Ellul, Richard Delorme, Samuele Cortese
BACKGROUND: Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs. OBJECTIVE: The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs. METHODS: Based on a pre-registered protocol (PROSPERO-CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials...
September 20, 2018: CNS Drugs
Anna Rosati, Salvatore De Masi, Renzo Guerrini
BACKGROUND: Ketamine is an emerging third-line medication for refractory status epilepticus, a medical and neurological emergency requiring prompt and appropriate treatment. Owing to its pharmacological properties, ketamine represents a practical alternative to conventional anaesthetics. OBJECTIVE: The objective of this study was to assess the efficacy and safety of ketamine to treat refractory status epilepticus in paediatric and adult populations. METHODS: We conducted a literature search using the PubMed database, Cochrane Database of Systematic Reviews and ClinicalTrials...
September 19, 2018: CNS Drugs
Andrew T Olagunju, Scott R Clark, Bernhard T Baune
BACKGROUND: Clozapine has unique efficacy for symptoms in treatment-resistant schizophrenia; however, symptomatic remission is not necessary nor sufficient for functional improvement. No study has pooled the effect of clozapine on psychosocial function across clinical trials. OBJECTIVE: We conducted a systematic review and meta-analysis to compare the effects of clozapine with other antipsychotics on psychosocial function, and described the predictors of functional outcome...
August 28, 2018: CNS Drugs
Mark Gudesblatt, Karl Wissemann, Myassar Zarif, Barbara Bumstead, Lori Fafard, Jeffrey Wilken, Karen Blitz, Marijean Buhse, Sourav Santra, Christophe Hotermans, Lily Lee
BACKGROUND: Cognitive impairment affects many patients with multiple sclerosis (MS). NeuroTrax, a computerized cognitive screen that can be administered during routine clinical care, provides a consistent, validated, objective cognitive profile measure with a global cognitive score (GCS) and seven individual domain scores. Natalizumab is an efficacious therapy for relapsing MS, demonstrating reductions in disability worsening and MS disease activity measured by magnetic resonance imaging...
August 24, 2018: CNS Drugs
Marita Zimmermann, Elizabeth Brouwer, Jeffrey A Tice, Matt Seidner, Anne M Loos, Shanshan Liu, Richard H Chapman, Varun Kumar, Josh J Carlson
BACKGROUND: Several disease-modifying therapies (DMTs) treat relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Few comprehensive cost-effectiveness analyses exist in this area, particularly from a payer perspective, despite rapidly increasing prices of DMTs. OBJECTIVE: We aimed to systematically compare cost effectiveness of all relevant DMTs for first-line treatment of RRMS, second-line treatment of RRMS, and first-line treatment of PPMS...
August 23, 2018: CNS Drugs
Dimitrios Papadopoulos, Dimos-Dimitrios D Mitsikostas
BACKGROUND: The likelihood to help or harm (LHH) is an absolute measure of the benefit versus risk profile of a medication, which can be used to assess the potential for benefit versus harm of different disease-modifying treatments (DMTs) for relapsing multiple sclerosis (R-MS) and facilitate clinical decision-making. OBJECTIVE: The objective of this study was to assess absolute differences in benefit:risk ratios of oral DMTs for R-MS, using LHH analysis with no evidence of disease activity (NEDA) as beneficial outcome...
August 1, 2018: CNS Drugs
Ferdinando Garetto, Ferdinando Cancelli, Romina Rossi, Marco Maltoni
Palliative sedation (PS) is performed in the terminally ill patient to manage one or more refractory symptoms. Proportional PS, which means that drugs can be titrated to the minimum effective dose, is the form most widely used. From a quarter to a third of all terminally ill patients undergo PS, with a quarter of these requiring continuous deep sedation. The prevalence of PS varies according to the care setting and case mix. The most frequent refractory physical symptoms are delirium and dyspnea, but PS is also considered for existential suffering or psychological distress, which is an extremely difficult and delicate issue to deal with...
October 2018: CNS Drugs
Janne Kaergaard Mortensen, Grethe Andersen
The great advances in acute stroke treatment during the last decades have changed life after stroke considerably. However, the use of intravenous thrombolysis and endovascular thrombectomy is limited by a relatively narrow time window or contraindications for treatment. Further, patients receiving acute reperfusion therapies may still have cognitive and emotional complications due to underlying brain infarcts even though physical problems may almost disappear. Consequently, stroke is still a frequent cause of adult disability and death worldwide, and an effort to identify additional treatments to enhance recovery, preferably also feasible in the time after the acute phase, is warranted...
October 2018: CNS Drugs
Raoul Sutter
No abstract text is available yet for this article.
October 2018: CNS Drugs
Christine Lebrun, Fanny Rocher
In the 1990s, the first disease-modifying therapies (DMTs) for multiple sclerosis (MS) were injectable immunomodulatory (IM) drugs, including four different interferon-β preparations and glatiramer acetate. Since 2000, more than 15 immunosuppressant (IS) drugs have been used, with a more or less specific action on inflammation. These include monoclonal antibodies targeting CTL4, the integrin receptor, the interleukin (IL)-2 receptor, CD19, CD20, CD52, and the sphingosine 1 phosphate family. The association between MS and cancer has long been investigated but has led to conflicting results...
October 2018: CNS Drugs
Simona Lattanzi, Francesco Brigo, Claudia Cagnetti, Eugen Trinka, Mauro Silvestrini
BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe developmental epileptic encephalopathy, and available interventions fail to control seizures in most patients. Cannabidiol (CBD) is a major chemical of marijuana, which has anti-seizure properties and different mechanisms of action compared with other approved antiepileptic drugs (AEDs). OBJECTIVE: The aim was to evaluate the efficacy and safety of CBD as adjunctive treatment for seizures in patients with LGS using meta-analytical techniques...
October 2018: CNS Drugs
David D Kim, Alasdair M Barr, Yunsun Chung, Jessica W Y Yuen, Mahyar Etminan, Bruce C Carleton, Randall F White, William G Honer, Ric M Procyshyn
BACKGROUND: Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxical induction of tics by first- and second-generation antipsychotics. OBJECTIVE: The objective of this systematic review was to better characterize tics as the potential adverse effect of antipsychotics. METHODS: A literature search was performed, with no language restriction, using the MEDLINE, EMBASE, and PsycINFO databases for all publications up to January 2018...
October 2018: CNS Drugs
Seok Jong Chung, Han Soo Yoo, Hye Sun Lee, Hyo Eun Jeong, Soo-Jong Kim, Jungsu S Oh, Jae Seung Kim, Young H Sohn, Phil Hyu Lee
BACKGROUND: It remains controversial whether late levodopa administration is a reasonable approach to reducing the risk of levodopa-induced dyskinesia in Parkinson's disease. OBJECTIVE: This study aimed to investigate the effects of levodopa sparing on the development of levodopa-induced dyskinesia. METHODS: We retrospectively reviewed medical records for patients with de novo Parkinson's disease who visited the Yonsei Parkinson Center between April 2009 and June 2015 and received at least 2 years of treatment...
October 2018: CNS Drugs
Massimiliano Mirabella, Luca Prosperini, Matteo Lucchini, Laura Boffa, Giovanna Borriello, Maria Chiara Buscarinu, Diego Centonze, Antonio Cortese, Chiara De Fino, Laura De Giglio, Giorgia Elia, Roberta Fantozzi, Elisabetta Ferraro, Ada Francia, Simona Galgani, Claudio Gasperini, Shalom Haggiag, Doriana Landi, Girolama Alessandra Marfia, Enrico Millefiorini, Fabrizia Monteleone, Viviana Nociti, Marco Salvetti, Eleonora Sgarlata, Carlo Pozzilli
BACKGROUND: Two phase III trials have demonstrated the clinical and radiological efficacy of delayed-release dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). However, data on its safety and effectiveness in real-world practice are still limited. OBJECTIVES: The aim of our study was to explore the safety and tolerability profile of DMF in RRMS. We also tried to identify individual variables associated with better clinical and radiological outcomes...
October 2018: CNS Drugs
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