Degenerative Neurological and Neuromuscular Disease最新文献

Transcranial magnetic stimulation (TMS) is a valuable technique for assessing the underlying neurophysiology associated with various neuropathologies, and is a unique tool for establishing potential neural mechanisms responsible for disease progression. Recently, repetitive TMS (rTMS) has been advanced as a potential therapeutic technique to treat selected neurologic disorders. In healthy individuals, rTMS can induce changes in cortical excitability. Therefore, targeting specific cortical areas affected by movement disorders theoretically may alter symptomology. This review discusses the evidence for the efficacy of rTMS in Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It is hoped that gaining a more thorough understanding of the timing and parameters of rTMS in individuals with neurodegenerative disorders may advance both clinical care and research into the most effective uses of this technology.

[This corrects the article DOI: 10.2147/DNND.S37341.].

Alzheimer's disease (AD) is a devastating neurodegenerative form of dementia with increasing incidence rates in most countries. AD is characterized by amyloid plaques and neurofibrillary tangles in the brains of AD individuals accompanied by global neuronal loss. The peptide amyloid-β (Aβ) aggregates to amyloid plaques in AD brains. As a result, many therapeutic approaches target Aβ. Human plasma and the plasma product intravenous immunoglobulin (IVIG) contain naturally-occurring anti-Aβ antibodies (Nabs-Aβ) that appear to reduce risks of developing AD. IVIG sequesters Aβ and thus interferes with AD progression. This study reviews the role of different Aβ species, Nabs-Aβ, preclinical data, and clinical studies of IVIG as potential AD treatments. The focus of this study is the outcomes of a recent Gammaglobulin Alzheimer's Partnership Phase III trial that did not reach primary endpoints, as well as efforts to compare IVIG with current anti-Aβ monoclonals such as bapineuzumab, solanezumab, and BIIB037. Moreover, this study critically examines current market and ethical consequences of potential off-label uses of IVIG, limits in IVIG supply, and subsequent challenges.

Multiple sclerosis (MS) is a common inflammatory demyelinating disorder of the central nervous system. It frequently affects females in their reproductive phase of life. Therefore, family planning, pregnancy, and breastfeeding are important issues in the management of MS, particularly with respect to counseling and drug treatment. This paper reviews currently available data on the outcome of pregnancies in MS patients and the influence of pregnancy on the course of the disease. We give an update on the use of various disease-modifying MS drugs during pregnancy and breastfeeding. In addition to established therapies such as interferon-β, glatiramer acetate, natalizumab, and fingolimod, we also discuss the state of knowledge about new agents such as dimethyl fumarate, teriflunomide, and alemtuzumab in the context of pregnancy and breastfeeding.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Recent developments have led to newer therapeutic options for disease treatment. A few studies have reported MS prevalence rates between 12 and 20 per 100,000 inhabitants nationwide in Argentina, and an incidence of 1.76 cases per 100,000 inhabitants per year. Considering the epidemiology of MS in Argentina, the total number of patients affected is estimated at 5,000-8,000 patients, with nearly 55%-65% of patients having a relapsing-remitting MS subtype of the disease. The aim of this review is to provide an overview of current and emerging treatments available in Argentina for patients with MS.

The worldwide increase in life expectancy is leading to an increase in age-dependent diseases, including nonfamilial, sporadic Alzheimer's disease (AD), which is the subject of this review. The etiology and pathophysiology of the disease is not fully understood, but present observations suggest that, in addition to genetic risk factors, environmental influences may be involved via epigenetic mechanisms. Currently, there is no effective treatment, but there are indications that lifestyle has an impact on the development of the disease. This view is supported by preclinical studies not only showing that human lifestyle-equivalent interventions have a positive effect on cognitive function in animal models of AD, but also indicating the involvement of underlying epigenetic mechanisms. After a brief overview of the most characteristic chromatin modifications, ie, DNA methylation and histone modifications, epigenetic changes associated with aging are considered, given that aging is the most important risk factor for AD. This is followed by a description of some epigenetic alterations recognized in AD. The impact of environmental factors and lifestyle on the epigenome is then considered. Epigenetic treatments with HDAC inhibitors and RNA-based drugs are considered, which - while still in preclinical stages - are promising for potential benefit. It is concluded that while awaiting results from clinical trials in progress, focusing on lifestyle adjustments with an epigenetic background are the best way to prevent/delay the onset of this devastating disease.

Interferon beta is a well established disease-modifying agent used for relapsing-remitting multiple sclerosis. Despite treatment, a relevant proportion of patients continue to experience clinical (ie, relapses, worsening of disability) and magnetic resonance imaging (MRI) activity. Early identification of responders and nonresponders to interferon beta is strongly recommended to select patients who need a prompt switch to another disease-modifying agent and to ultimately avoid accumulation of fixed disability over time. Detecting responders and nonresponders to interferon beta can be challenging, mainly because of the lack of a clear and shared clinical definition of response to treatment. Clinical features at the start of treatment should be considered as prognostic factors, but MRI parameters assessed during treatment, such as contrast-enhancing lesions or new T2-hyperintense lesions, may be sensitive markers of response to interferon beta. Quantitative scoring systems derived from a combination of relapses and MRI activity have recently been proposed as practical tools for use in the everyday clinical setting. Blood biomarkers, such as neutralizing antibodies to interferon beta and Myxovirus resistance protein A, provide further useful information for detecting responders and nonresponders to interferon beta. However, since the presence of neutralizing antibodies can only partially explain the nonresponse to interferon beta, biomarkers of interferon beta activity possibly related to the pathogenesis of the disease could represent a future step toward a tailored, long-lasting effective treatment against multiple sclerosis.

People with neurogenic overactive bladder from either multiple sclerosis or spinal cord injury often suffer significant morbidity and decreased quality of life. Here we review the pathophysiology of neurogenic overactive bladder and the impact it can have on people with multiple sclerosis or spinal cord injury. We also address the various traditional treatment options and focus on the use of botulinum toxin A (specifically onabotulinumtoxinA) for this condition.

Multiple sclerosis (MS) is a complex autoimmune disease that impairs the central nervous system (CNS). The neurological disability and clinical course of the disease is highly variable and unpredictable from one patient to another. The cause of MS is still unknown, but it is thought to occur in genetically susceptible individuals who develop disease due to a nongenetic trigger, such as altered metabolism, a virus, or other environmental factors. MS patients develop progressive, irreversible, neurological disability associated with neuronal and axonal damage, collectively known as neurodegeneration. Neurodegeneration was traditionally considered as a secondary phenomenon to inflammation and demyelination. However, recent data indicate that neurodegeneration develops along with inflammation and demyelination. Thus, MS is increasingly recognized as a neurodegenerative disease triggered by an inflammatory attack of the CNS. While both inflammation and demyelination are well described and understood cellular processes, neurodegeneration might be defined by a diverse pool of any of the following: neuronal cell death, apoptosis, necrosis, and virtual hypoxia. In this review, we present multiple theories and supporting evidence that identify common biological processes that contribute to neurodegeneration in MS.

The process of axonal transport serves to move components over very long distances on microtubule tracks in order to maintain neuronal viability. Molecular motors - kinesin and dynein - are essential for the movement of neuronal cargoes along these tracks; defects in this pathway have been implicated in the initiation or progression of some neurodegenerative diseases, suggesting that this process may be a key contributor in neuronal dysfunction. Recent work has led to the identification of some of the motor-cargo complexes, adaptor proteins, and their regulatory elements in the context of disease proteins. In this review, we focus on the assembly of the amyloid precursor protein, huntingtin, mitochondria, and the RNA-motor complexes and discuss how these may be regulated during long-distance transport in the context of neurodegenerative disease. As knowledge of these motor-cargo complexes and their involvement in axonal transport expands, insight into how defects in this pathway contribute to the development of neurodegenerative diseases becomes evident. Therefore, a better understanding of how this pathway normally functions has important implications for early diagnosis and treatment of diseases before the onset of disease pathology or behavior.