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Therapeutic Advances in Neurological Disorders

H N Beadnall, C Wang, W Van Hecke, A Ribbens, T Billiet, M H Barnett
Background: Whole brain atrophy (WBA) estimates in multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. We compare Structural Image Evaluation using Normalisation of Atrophy (SIENA) with the icobrain longitudinal pipeline (icobrain long), for assessment of longitudinal WBA in MS patients. Methods: Magnetic resonance imaging (MRI) scan pairs [1.05 (±0.15) year separation] from 102 MS patients were acquired on the same 3T scanner...
2019: Therapeutic Advances in Neurological Disorders
Michelle Alexander-Curtis, Rick Pauls, Julie Chao, John J Volpi, Philip M Bath, Todd A Verdoorn
Acute ischemic stroke (AIS) remains a major cause of death and disability throughout the world. The most severe form of stroke results from large vessel occlusion of the major branches of the Circle of Willis. The treatment strategies currently available in western countries for large vessel occlusion involve rapid restoration of blood flow through removal of the offending blood clot using mechanical or pharmacological means (e.g. tissue plasma activator; tPA). This review assesses prospects for a novel pharmacological approach to enhance the availability of the natural enzyme tissue kallikrein (KLK1), an important regulator of local blood flow...
2019: Therapeutic Advances in Neurological Disorders
Egor Dzyubenko, Daniel Manrique-Castano, Christoph Kleinschnitz, Andreas Faissner, Dirk M Hermann
Neuroinflammation is one of the key components contributing to the devastating outcome of ischemic stroke. Starting with stroke onset, inflammatory processes contribute both to cell damage and tissue remodeling. The early release of alarmins triggers the upregulation of multiple proinflammatory cytokines, resulting in the compromised integrity of the blood-brain barrier. From this moment on, the infiltration of peripheral immune cells, reactive gliosis and extracellular matrix (ECM) alterations become intricately intertwined and act as one unit during the tissue remodeling...
2018: Therapeutic Advances in Neurological Disorders
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2018: Therapeutic Advances in Neurological Disorders
Lucia Ruggiero, Rosa Iodice, Marcello Esposito, Raffaele Dubbioso, Stefano Tozza, Floriana Vitale, Lucio Santoro, Fiore Manganelli
Background: Ataluren was approved for the treatment of nmDMD, both the efficacy and safety have been previously reported only from clinical trials but no report exists about real-life experience. Patient/methods: we describe three Italian children with nmDMD treated with ataluren for 1 year. Measurements were made every 3 months and was evaluated the 6-Minute Walking Distance (6MWD). Results: Case1 involves a patient with a 6MWD at T0 of 360 m, who started ataluren therapy at age 10 years...
2018: Therapeutic Advances in Neurological Disorders
Min-Suk Yoon, Kalliopi Pitarokoili, Dietrich Sturm, Aiden Haghikia, Ralf Gold, Anna Lena Fisse
Background: The aim of this work was to report a case of an acute motor and sensory axonal neuropathy (AMSAN) treated with propionate to evaluate its therapeutic potential in AMSAN. Materials and methods: The patient was investigated by clinical examination, electroneurography, high-resolution nerve ultrasound and confocal corneal microscopy at baseline and the 2 month follow up. We compared the outcome with those of five other patients with acute motor axonal neuropathy (AMAN) and AMSAN of who were referred to our neurology department in the past 5 years...
2018: Therapeutic Advances in Neurological Disorders
Yvonne Geissbühler, Jere Vile, Gideon Koren, Morgane Guennec, Helmut Butzkueven, Hugh Tilson, Thomas M MacDonald, Kerstin Hellwig
Background and Methods: Limited data are available on the safety of fingolimod in pregnant women. We estimated the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS) exposed to fingolimod either shortly before or during pregnancy in prospectively collected cases from clinical trials, observational studies, surveillance programs, and spontaneous reports. Results: The prevalence of major malformations among live births does not appear to be significantly higher than those in the general population and the unexposed MS population...
2018: Therapeutic Advances in Neurological Disorders
Samis Zella, Janina Kneiphof, Aiden Haghikia, Ralf Gold, Dirk Woitalla, Jan Thöne
Background: Neurosarcoidosis occurs in about 5-15% of patients with sarcoidosis. Therapy with corticosteroids is generally accepted as the first-line medication, followed by various immunomodulating and cytotoxic agents or combined therapy. However, some patients show an unsatisfactory outcome or have adverse events and require novel treatment strategies. Methods: We describe three patients with systemic sarcoidosis and central nervous system involvement who received CD20-targeted B-cell depletion with rituximab...
2018: Therapeutic Advances in Neurological Disorders
Marco Puthenparampil, Chiara Cazzola, Sofia Zywicki, Lisa Federle, Erica Stropparo, Mariagiulia Anglani, Francesca Rinaldi, Paola Perini, Paolo Gallo
Background: Cortical lesions (CLs) are typical of multiple sclerosis (MS) and have been recently incorporated in MS diagnostic criteria. Thus, the 'no evidence of disease activity' (NEDA) definition should now include CLs. The aim of this study was to evaluate the NEDA3 + CL status in natalizumab- or fingolimod-treated relapsing remitting MS (RMS) patients. Methods: Natalizumab- or fingolimod-treated RMS patients were enrolled in a 2-year longitudinal study based on clinical and magnetic resonance imaging (MRI) evaluations performed respectively biannually and annually...
2018: Therapeutic Advances in Neurological Disorders
Kohei Okuyama, Miho Ogura, Michiyuki Kawakami, Kengo Tsujimoto, Kohsuke Okada, Kazuma Miwa, Yoko Takahashi, Kaoru Abe, Shigeo Tanabe, Tomofumi Yamaguchi, Meigen Liu
Background: The combination of motor imagery (MI) and afferent input with electrical stimulation (ES) enhances the excitability of the corticospinal tract compared with motor imagery alone or electrical stimulation alone. However, its therapeutic effect is unknown in patients with hemiparetic stroke. We performed a preliminary examination of the therapeutic effects of MI + ES on upper extremity (UE) motor function in patients with chronic stroke. Methods: A total of 10 patients with chronic stroke demonstrating severe hemiparesis participated...
2018: Therapeutic Advances in Neurological Disorders
Philipp Albrecht, Ingrid Kristine Bjørnå, David Brassat, Rachel Farrell, Peter Feys, Jeremy Hobart, Raymond Hupperts, Michael Linnebank, Jožef Magdič, Celia Oreja-Guevara, Carlo Pozzilli, Antonio Vasco Salgado, Tjalf Ziemssen
Prolonged-release (PR) fampridine is the only approved medication to improve walking in multiple sclerosis (MS), having been shown to produce a clinically meaningful improvement in walking ability in the subset of MS patients with Expanded Disability Status Scale 4-7. Recent responder subgroup analyses in the phase III ENHANCE study show a large effect size in terms of an increase of 20.58 points on the patient-reported 12-item MS Walking Scale in the 43% of patients classified as responders to PR-fampridine, corresponding to a standardized response mean of 1...
2018: Therapeutic Advances in Neurological Disorders
Benjamin Stolte, Andreas Totzeck, Kathrin Kizina, Saskia Bolz, Lena Pietruck, Christoph Mönninghoff, Nika Guberina, Denise Oldenburg, Michael Forsting, Christoph Kleinschnitz, Tim Hagenacker
Background: Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) and the first approved drug for the treatment of spinal muscular atrophy (SMA). However, progressive neuromyopathic scoliosis and the presence of spondylodesis can impede lumbar punctures in SMA patients. Our aim was to assess the feasibility and safety of the treatment in adults with SMA. Methods: For the intrathecal administration of nusinersen, we performed conventional, fluoroscopy-assisted and computer tomography (CT)-guided lumbar punctures in adult patients with type 2 and type 3 SMA...
2018: Therapeutic Advances in Neurological Disorders
Sarah Löw, Catherine H Han, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL), confined to the brain, eyes, spinal cord or leptomeninges without systemic involvement. Overall prognosis, diagnosis and management of PCNSL differ from other types of NHL. Prompt diagnosis and initiation of treatment are vital to improving clinical outcomes. PCNSL is responsive to radiation therapy, however whole-brain radiotherapy (WBRT) inadequately controls the disease when used alone and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients...
2018: Therapeutic Advances in Neurological Disorders
Chi-Hung Liu, Yu-Sheng Lin, Ching-Chi Chi, Chia-Wei Liou, Jiann-Der Lee, Tsung-I Peng, Tsong-Hai Lee
Background: To compare the long-term clinical outcomes of different antihypertensive drugs in stable patients after acute hemorrhagic stroke (HS). Methods: From January 2001 to December 2013, patients with first-ever primary HS were identified in the National Health Insurance Research Database, Taiwan. Patients with traumatic intracerebral hemorrhage and secondary HS were excluded. Those with first-ever HS were recruited and classified into three groups: (1) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB); (2) calcium channel blocker (CCB); and (3) other antihypertensive drugs (comparison) groups...
2018: Therapeutic Advances in Neurological Disorders
Marinos C Dalakas
Patients with advanced malignancies treated with immune checkpoint inhibitors are at increased risk for developing immune-related neurological complications. It is a phenomenon of immunological twist when immunotherapy against co-stimulatory molecules activates previously normal T cells to kill tumor cells but, in so doing, the T cells become unrestrained, triggering other autoimmune diseases for which conventional immunotherapy is needed. The most common autoimmune neurological diseases, usually occurring within 2-12 weeks after immune checkpoint inhibitor initiation, include: inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis...
2018: Therapeutic Advances in Neurological Disorders
Dirk M Hermann, Christoph Kleinschnitz, Matthias Gunzer
Polymorphonuclear neutrophil granulocytes (PMNs) are part of the early post-ischemic immune response that orchestrates the removal of infarcted brain tissue. PMNs contribute to secondary brain injury in experimental stroke models. In human patients, high PMN-to-lymphocyte ratios in peripheral blood are predictive of poor stroke outcome. Following earlier studies indicating that the cerebral microvasculature forms an efficient barrier that impedes PMN brain entry even under conditions of ischemia, more recent studies combining intravital two-photon microscopy and ex vivo immunohistochemistry unequivocally demonstrated the accumulation of PMNs in the ischemic brain parenchyma...
2018: Therapeutic Advances in Neurological Disorders
Ilya Kister, Tamar E Bacon, Gary R Cutter
Background: Short-term disease progression is well documented in clinical trials, but there are limited published data on disease course in real-life practice. Methods: Patient-derived Multiple Sclerosis Severity Score (PMSSS), a disease severity rank score, was computed at each visit for consecutive MS patients attending two large, ethnically diverse MS centers in New York metropolitan area. Disability was assessed via Patient-Determined Disease Steps (PDDS). Clinicians recorded disease subtype and relapse status at each visit, but did not rate disability...
2018: Therapeutic Advances in Neurological Disorders
Emanuele D'Amico, Aurora Zanghì, Graziella Callari, Giovanna Borriello, Antonio Gallo, Giusi Graziano, Paola Valentino, Maria Buccafusca, Salvatore Cottone, Giuseppe Salemi, Paolo Ragonese, Roberto Bruno Bossio, Renato Docimo, Luigi Maria Edoardo Grimaldi, Carlo Pozzilli, Gioacchino Tedeschi, Mario Zappia, Francesco Patti
Background: The aim of the study was to evaluate the achievement of 'no evidence of disease activity' (NEDA) over a 12-month period in a large multicenter population with relapsing remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a propensity-score adjustment. Methods: A time-to-event method was used to determine the percentages of patients with RRMS (pwRRMS) in both groups achieving NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new T2/gadolinium-enhancing brain lesions)...
2018: Therapeutic Advances in Neurological Disorders
Douglas L Arnold, Shulian Shang, Qunming Dong, Matthias Meergans, Maria L Naylor
Background: No evidence of disease activity (NEDA) is a composite measurement, incorporating clinical and magnetic resonance imaging (MRI) elements of disease activity to sensitively evaluate the therapeutic efficacy of treatments for relapsing-remitting multiple sclerosis (RRMS). Objective: To assess the NEDA status of patients treated with peginterferon β-1a in the ADVANCE and ATTAIN studies and explore its predictive value on longer-term clinical outcomes. Methods: ATTAIN was a 2-year extension of the pivotal 2-year ADVANCE study of peginterferon β-1a for RRMS...
2018: Therapeutic Advances in Neurological Disorders
Gaby Enzmann, Soghra Kargaran, Britta Engelhardt
Reperfusion injury following ischemic stroke is a complex pathophysiological process involving numerous mechanisms ranging from the release of excitatory amino acids and ion disequilibrium to the induction of apoptosis and necrosis, to oxidative stress and inflammation. The migration of neutrophils into the brain parenchyma and release of their abundant proteases are generally considered the main cause of neuronal cell death and acute reperfusion injury following ischemic stroke. Recent findings in experimental and human stroke have challenged this view, as the majority of neutrophils were rather found to accumulate within the neurovascular unit (NVU) and the subarachnoid space (SAS) where they remain separated from the brain parenchyma by the glia limitans ...
2018: Therapeutic Advances in Neurological Disorders
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