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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
Scott D Newsome, Thomas F Scott, Douglas L Arnold, Gereon Nelles, Serena Hung, Yue Cui, Shulian Shang, Maria L Naylor, Marcelo Kremenchutzky
Background: ADVANCE was a phase III trial of the efficacy and safety of subcutaneous peginterferon beta-1a 125 µg every 2 or 4 weeks in patients with relapsing-remitting multiple sclerosis (RRMS). ATTAIN was a 2-year extension study of ADVANCE. The aim was to evaluate the long-term safety, tolerability, and efficacy of peginterferon beta-1a 125 µg every 2 or 4 weeks in ATTAIN. Methods: ADVANCE dosing schedules were maintained in ATTAIN, except that every-4-weeks dosing patients were switched to every-2-weeks dosing after conversion of the study to an open-label protocol...
2018: Therapeutic Advances in Neurological Disorders
Manabu Araki, Youwei Lin, Hirohiko Ono, Wakiro Sato, Takashi Yamamura
Ehlers-Danlos syndrome (EDS) is a heterogeneous heritable connective tissue disorder with various neurological manifestations, including chronic pain. The neurological manifestations in EDS are often regarded as being caused by the associated musculoskeletal disorders or polyneuropathy. Here, we present two patients with hypermobile EDS (hEDS), presenting with relapsing central nervous system (CNS) manifestations. Although the two patients showed relapsing signs of CNS manifestations like multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD), they were unique in that they had widespread opioid-dependent chronic pain, which is not consistent with the symptoms of MS/NMOSD...
2018: Therapeutic Advances in Neurological Disorders
Mingqin Zhu, Xiuzhe Wang, Li Sun, Marianne Schultzberg, Erik Hjorth
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and dementia. Accumulating evidence suggests that inflammation is involved in the pathogenesis of AD. Epidemiological studies suggest that use of anti-inflammatory drugs is associated with a lower incidence of AD. However, clinical trials with anti-inflammatory drugs have not been successful. Recent studies have shown that inflammation is resolved by a process that is mediated by a group of lipid mediators, so called specialized pro-resolving lipid mediators (SPMs)...
2018: Therapeutic Advances in Neurological Disorders
Lara Diem, Krassen Nedeltchev, Timo Kahles, Lutz Achtnichts, Oliver Findling
Background: Natalizumab significantly reduces the disease activity in patients with relapsing-remitting multiple sclerosis but due to the risk of progressive multifocal leukoencephalopathy it is often discontinued. Fingolimod is seen as an alternative, but there are no long-term analyses of the efficacy of fingolimod in this setting using the no evidence of disease activity (NEDA)-3 criteria. We provide an assessment of patients who discontinued natalizumab and switched to fingolimod or other treatments by evaluating the proportion of patients who fulfil NEDA-3 criteria after prolonged follow-up periods...
2018: Therapeutic Advances in Neurological Disorders
Laura Ramiro, Alba Simats, Teresa García-Berrocoso, Joan Montaner
Stroke is the fifth leading cause of death and the most frequent cause of disability worldwide. Currently, stroke diagnosis is based on neuroimaging; therefore, the lack of a rapid tool to diagnose stroke is still a major concern. In addition, therapeutic approaches to combat ischemic stroke are still scarce, since the only approved therapies are directed toward restoring blood flow to the affected brain area. However, due to the reduced time window during which these therapies are effective, few patients benefit from them; therefore, alternative treatments are urgently needed to reduce stroke brain damage in order to improve patients' outcome...
2018: Therapeutic Advances in Neurological Disorders
Wolfgang Wick, Matthias Osswald, Antje Wick, Frank Winkler
The diagnosis of a glioblastoma is mainly made on the basis of their microscopic appearance with the additional determination of epigenetic as well as mutational analyses as deemed appropriate and taken into account in different centers. How far the recent discovery of tumor networks will stimulate novel treatments is a subject of intensive research. A tissue diagnosis is the mainstay. Regardless of age, patients should undergo a maximal safe resection. Magnetic resonance imaging is the surrogate parameter of choice for follow up...
2018: Therapeutic Advances in Neurological Disorders
Antoine Drieu, Damien Levard, Denis Vivien, Marina Rubio
So far, intravenous tissue-type plasminogen activator (tPA) and mechanical removal of arterial blood clot (thrombectomy) are the only available treatments for acute ischemic stroke. However, the short therapeutic window and the lack of specialized stroke unit care make the overall availability of both treatments limited. Additional agents to combine with tPA administration or thrombectomy to enhance efficacy and improve outcomes associated with stroke are needed. Stroke-induced inflammatory processes are a response to the tissue damage due to the absence of blood supply but have been proposed also as key contributors to all the stages of the ischemic stroke pathophysiology...
2018: Therapeutic Advances in Neurological Disorders
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