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Therapeutic Advances in Neurological Disorders

Christopher Jan Schwarzbach, Anne Ebert, Michael G Hennerici, Eva Neumaier-Probst, Michael Platten, Marc Fatar
Background: The safety of systemic thrombolysis in patients with intracranial tumor and cavernoma are unknown. So far evidence is limited to a number of case reports and few case series or unspecified data based on population-based analysis. Our aim was to comprehend the risk of systemic thrombolysis in these patients. Methods: Patients with additional evidence of intracranial tumor or cavernoma who received IV tissue plasminogen activator (t-PA) treatment at our comprehensive stroke center over a period of 7 years were identified in our stroke database and compared to the same number of matched control subjects without any evidence of intracranial tumor and cavernoma...
2018: Therapeutic Advances in Neurological Disorders
Valeria Parente, Stefania Corti
Spinal muscular atrophy (SMA) is a progressive, recessively inherited neuromuscular disease, characterized by the degeneration of lower motor neurons in the spinal cord and brainstem, which leads to weakness and muscle atrophy. SMA currently represents the most common genetic cause of infant death. SMA is caused by the lack of survival motor neuron (SMN) protein due to mutations, which are often deletions, in the SMN1 gene. In the absence of treatments able to modify the disease course, a considerable burden falls on patients and their families...
2018: Therapeutic Advances in Neurological Disorders
Jennifer Jeck, Rebecca Kassubek, Jan Coburger, Simone Edenhofer, Stefan S Schönsteiner, Albert C Ludolph, Bernd Schmitz, Jens Engelke, Regine Mayer-Steinacker, Jan Lewerenz, Lars Bullinger
Background: Despite multidisciplinary treatment approaches, the prognosis for patients with high-grade glioma (HGG) is poor, with a median overall survival (OS) of 14.6 months for glioblastoma multiforme (GB). As high levels of vascular endothelial growth factor A (VEGF) are found in HGG, targeted anti-antiangiogenic therapy using the humanized monoclonal antibody bevacizumab (BEV) was studied in a series of clinical trials. Still, the discrepancy of BEV's efficacy with regard to initial clinical and radiological response and its reported failure to prolong survival remains to be explained...
2018: Therapeutic Advances in Neurological Disorders
Alberto Picca, Giulia Berzero, Marc Sanson
The 2016 WHO classification of Tumors of the Central Nervous System brought major conceptual and practical changes in the classification of diffuse gliomas, by combining molecular features and histology into 'integrated' diagnoses. In diffuse gliomas, molecular profiling has thus become essential for nosological purposes, as well as to plan adequate treatment strategies and identify patients susceptible of target therapy. WHO grade II (low grade) and grade III (anaplastic) diffuse gliomas form a heterogeneous group of neoplasms, also known as 'lower-grade gliomas', characterized by a wide range of malignant potential...
2018: Therapeutic Advances in Neurological Disorders
Renato Mantegazza, Carlo Antozzi
The prognosis for patients with myasthenia gravis (MG) has improved significantly over the past half century, including substantial reductions in mortality and morbidity. However, approximately 10% of patients fails to respond adequately to current therapies and are considered treatment refractory, or treatment intolerant, and up to 80% have disease that fails to achieve complete stable remission. Although patients with autoantibodies to muscle-specific tyrosine kinase (anti-MuSK positive) are more likely to become treatment refractory than those with autoantibodies to the acetylcholine receptor (anti-AChR positive), each of these serotypes is substantially represented in the refractory MG population...
2018: Therapeutic Advances in Neurological Disorders
Marinos C Dalakas
Polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy is the most common paraproteinemic neuropathy, comprising a clinicopathologically and immunologically distinct entity. The clinical spectrum spans from distal paresthesias and mild gait imbalance to more severe sensory ataxia, with falls and a varying degree of distal sensorimotor deficits. In approximately 75% of patients, the monoclonal IgM immunoreacts with myelin-associated glycoprotein (MAG) and sulfoglucuronyl glycosphingolipid (SGPG), or other peripheral nerve glycolipids that serve as antigens...
2018: Therapeutic Advances in Neurological Disorders
Xiaolei Liu, Roi Treister, Magdalena Lang, Anne Louise Oaklander
Objectives: Small-fiber polyneuropathy (SFPN) has various underlying causes, including associations with systemic autoimmune conditions. We have proposed a new cause; small-fiber-targeting autoimmune diseases akin to Guillain-Barré and chronic inflammatory demyelinating polyneuropathy (CIDP). There are no treatment studies yet for this 'apparently autoimmune SFPN' (aaSFPN), but intravenous immunoglobulin (IVIg), first-line for Guillain-Barré and CIDP, is prescribed off-label for aaSFPN despite very high cost...
2018: Therapeutic Advances in Neurological Disorders
Giancarlo Comi, Stuart Cook, Kottil Rammohan, Per Soelberg Sorensen, Patrick Vermersch, Abidemi K Adeniji, Fernando Dangond, Gavin Giovannoni
Background: The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods: Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3...
2018: Therapeutic Advances in Neurological Disorders
Stephan Schmidt, Jürgen Koehler, Christine Winterstein, Petra Schicklmaier, Boris Kallmann
Background: In relapsing-remitting multiple sclerosis (RRMS), 'no evidence of disease activity' (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management. Methods: EPIDEM was a multicenter non-interventional retrospective study in a large cohort of RRMS patients receiving injectable DMTs for at least 2 years in outpatient centers throughout Germany...
2018: Therapeutic Advances in Neurological Disorders
Veit Becker, Volker Heeschen, Katrin Schuh, Heinke Schieb, Tjalf Ziemssen
Background: As patients with multiple sclerosis (MS) require lifelong treatment, optimization of therapy with respect to efficacy and safety is needed to limit long-term disease progression. Patients with MS also need a range of health-related services. Satisfaction with these as well as treatment is clinically relevant because satisfied patients are more likely to adhere to therapy. The aim of this study was to determine the status of patient satisfaction and of healthcare services in 70 specialized MS centres in Germany...
2018: Therapeutic Advances in Neurological Disorders
César Fernández-de-Las-Peñas, Juan J Fernández-Muñoz, María Palacios-Ceña, Paula Parás-Bravo, Margarita Cigarán-Méndez, Esperanza Navarro-Pardo
Current research into the pathogenesis of tension-type headache (TTH) and migraine is focused on altered nociceptive pain processing. Among the potential factors that influence sensitization mechanisms, emotional stress, depression, or sleep disorders all have an essential role: they increase the excitability of nociceptive firing and trigger hyperalgesic responses. Sleep disturbances and headache disorders share common brain structures and pathogenic mechanisms and TTH, migraine, and sleep disturbances often occur together; for example, 50% of individuals who have either TTH or migraine have insomnia...
2018: Therapeutic Advances in Neurological Disorders
Sebastian Fischer, Werner Weber
The treatment of stroke caused by intracranial vessel occlusion with intravenous recombinant tissue plasminogen activator (rt-PA) was the only evidence-based treatment option for a long time. Nevertheless the response rate was disappointing in large vessel occlusions. Five studies that evaluated the efficacy of mechanical thrombectomy published in 2015 proved a significant clinical benefit for selected patients suffering from acute ischemic stroke. These results are the basis for extensive technical, institutional, and personal structural changes in the neurovascular field of stroke treatment...
2018: Therapeutic Advances in Neurological Disorders
Linda J Stephen, Martin J Brodie
Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein...
2018: Therapeutic Advances in Neurological Disorders
Jun Wan Shin, Jong-Min Lee
Over the past few decades, as gene discovery methods and sequencing technologies have evolved, many genetic variations that significantly increase the risk of or cause neurodegenerative diseases have been identified. However, knowledge of those pathogenic mutations and subsequent mechanism-focused studies has rarely yielded effective treatments, warranting alternative strategies for refining rational therapeutic targets. Nevertheless, with the evolution of gene targeting methods, it has been increasingly recognized that the disease-causing gene itself is the best therapeutic target even when we do not have a full understanding of its biological functions...
2018: Therapeutic Advances in Neurological Disorders
Marco Puthenparampil, Francesca Rinaldi, Lisa Federle, Chiara Cazzola, Paola Perini, Paolo Gallo
Background: The cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS. Methods: A total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49)...
2018: Therapeutic Advances in Neurological Disorders
Jason Margolesky, Carlos Singer
Motor fluctuations complicate the treatment of patients with Parkinson's disease receiving levodopa. Extended-release carbidopa-levodopa has a pharmacokinetic profile that provides a more continuous levodopa serum concentration. Patients taking this formulation can expect longer duration of action and fewer doses per day, similar clinical improvement when compared to other levodopa formulations, and with a theoretically lower risk of developing motor fluctuations. Several studies, including three randomized control trials provide evidence for the efficacy, safety and tolerability of extended release carbidopa-levodopa in patients with both early and advanced Parkinson's disease are reviewed here...
2018: Therapeutic Advances in Neurological Disorders
Johannes Dorst, Albert C Ludolph, Annemarie Huebers
In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important...
2018: Therapeutic Advances in Neurological Disorders
Donghua Mi, Pingli Wang, Bo Yang, Yuehua Pu, Zhonghua Yang, Liping Liu
Background: Hyperglycemia has been considered a predictor of stroke outcomes. In this article we study the correlation between blood glucose levels within the first 24 h after stroke onset and patients' outcomes in mortality and hemorrhagic transformations. Methods: Ninety-one non-diabetic patients with acute ischemic stroke admitted to a neurological intensive unit were recruited. Their blood glucose was measured twice within 6 h (baseline) and at every hour after stroke onset...
2018: Therapeutic Advances in Neurological Disorders
Yong-Won Shin, Soon-Tae Lee, Kyung-Il Park, Keun-Hwa Jung, Ki-Young Jung, Sang Kun Lee, Kon Chu
Autoimmune encephalitis is one of the most rapidly growing research topics in neurology. Along with discoveries of novel antibodies associated with the disease, clinical experience and outcomes with diverse immunotherapeutic agents in the treatment of autoimmune encephalitis are accumulating. Retrospective observations indicate that early aggressive treatment is associated with better functional outcomes and fewer relapses. Immune response to first-line immunotherapeutic agents (corticosteroids, intravenous immunoglobulin, plasma exchange, and immunoadsorption) is fair, but approximately half or more of patients are administered second-line immunotherapy (rituximab and cyclophosphamide)...
2018: Therapeutic Advances in Neurological Disorders
Chia-Chun Chiang, Amaal J Starling
Chronic migraine is a debilitating neurobiological disorder that affects approximately 1.4-2.2% of the population worldwide. Patients with chronic migraine have 15 or more headache days per month, with at least 8 days per month that meet the criteria for migraine. Injection of onabotulinumtoxinA, using a standardized injection protocol, was approved by the US Food and Drug Administration in 2010 for the treatment of chronic migraine. The approval was made based on results from two large, randomized, double-blind placebo-controlled trials: the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials...
December 2017: Therapeutic Advances in Neurological Disorders
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