Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.
Antibodies, Monoclonal, Humanized ; Central Nervous System ; Humans ; Hypogonadism ; Interferon-beta ; Mitochondrial Diseases ; Mitoxantrone ; Multiple Sclerosis ; Natalizumab ; Ophthalmoplegia ; Peptides ; Quality of Life ; Recurrence ; Urinary Bladder ; Young Adult

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.
Antibodies, Monoclonal, Humanized ; Central Nervous System ; Humans ; Hypogonadism ; Interferon-beta ; Mitochondrial Diseases ; Mitoxantrone ; Multiple Sclerosis ; Natalizumab ; Ophthalmoplegia ; Peptides ; Quality of Life ; Recurrence ; Urinary Bladder ; Young Adult

White matter hyperintensity (WMH) is commonly observed on the brain MRI of elderly subjects. It has been considered as an important biomarker for the micro-vascular damages of white matter of the brain. Aging, hypertension, diabetes mellitus, and hyperhomocysteinemia have been associated with WMH development. WMH is an important risk factor for the vascular dementia (VD), however it also considered as one of risk factors for conversion of mild cognitive impairment to dementia and progression of Alzheimer's disease (AD). WMH has impact on gait, bladder control, and fine motor coordination. It also has negative effects on memory retrieval, mental flexibility, mental processing speed, and executive function by disconnecting nerve fibers that convey signals for normal cognition. Control of vascular risk factors can delay progression of WMH and this may be beneficial for VD as well as AD with ischemic changes, especially in the early state of diseases. In this paper, we will review clinical significance of WMH and three important diseases, subcortical vascular dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and cerebral amyloid angiopathy that associated with cerebral micro-vascular damages.
Aged ; Aging ; Alzheimer Disease ; Brain ; CADASIL ; Cerebral Amyloid Angiopathy ; Cognition ; Dementia ; Dementia, Vascular ; Diabetes Mellitus ; Executive Function ; Gait ; Humans ; Hyperhomocysteinemia ; Hypertension ; Memory ; Mild Cognitive Impairment ; Nerve Fibers ; Pliability ; Risk Factors ; Urinary Bladder

Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widely applied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugs recently approved for MS treatment represent significant advances in therapy. The oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis of the risks and benefits is required. Three oral drugs have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews the mechanisms of action, safety, and efficacy of these drugs and two other drugs that have yielded positive results in phase III trials: cladribine and laquinimod.
Cladribine ; Compliance ; Dimethyl Fumarate ; Fingolimod Hydrochloride ; Multiple Sclerosis* ; Patient Satisfaction ; Risk Assessment

Neuromyelitis optica (NMO) is an idiopathic inflammatory disorder of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. In Asia, NMO has long been considered a subtype of multiple sclerosis (MS). However, recent clinical, pathological, immunological, and imaging studies have suggested that NMO is distinct from MS. This reconsideration of NMO was initially prompted by the discovery of a specific antibody for NMO (NMO-IgG) in 2004. NMO-IgG is an autoantibody that targets aquaporin-4 (AQP4), the most abundant water channel in the CNS; hence, it was named anti-AQP4 antibody. Since it demonstrated reasonable sensitivity and high specificity, anti-AQP4 antibody was incorporated into new diagnostic criteria for NMO.The spectrum of NMO is now known to be wider than was previously recognized and includes a proportion of patients with recurrent, isolated, longitudinally extensive myelitis or optic neuritis, and longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease or with brain lesions typical of NMO. In this context, a new concept of "NMO spectrum disorders" was recently introduced. Furthermore, seropositivity for NMO-IgG predicts future relapses and is recognized as a prognostic marker for NMO spectrum disorders. Humoral immune mechanisms, including the activation of B-cells and the complement pathway, are considered to play important roles in NMO pathogenesis. This notion is supported by recent studies showing the potential pathogenic role of NMO-IgG as an initiator of NMO lesions. However, a demonstration of the involvement of NMO-IgG by the development of active immunization and passive transfer in animal models is still needed. This review focuses on the new concepts of NMO based on its pathophysiology and clinical characteristics. Potential management strategies for NMO in light of its pathomechanism are also discussed.
Asia ; Autoimmune Diseases ; B-Lymphocytes ; Brain ; Central Nervous System ; Complement System Proteins ; Humans ; Light ; Models, Animal ; Multiple Sclerosis ; Myelitis ; Neuromyelitis Optica ; Optic Nerve ; Optic Neuritis ; Recurrence ; Sensitivity and Specificity ; Spinal Cord ; Vaccination ; Water

BACKGROUND: An acute ischemic infarction can occur in patients admitted to a nonneurology department, which can result in a delay in the diagnosis that could produce a poor outcome. The aim of this study was to identify the clinical and radiologic features of ischemic stroke diagnosed during consultations in nonneurology departments. METHODS: Acute ischemic stroke patients who were admitted to a neurology department or who were diagnosed after a consultation to a neurology department between October 2007 and February 2009 were enrolled. Acute ischemic stroke was diagnosed by a stroke neurologist with the aid of diffusion-weighted MRI. Clinical variables [age, sex, risk factors, initial score on the National Institutes of Health Stroke Scale, stroke subtype, and modified Rankin scale (mRS) score at 3 months] were obtained. Poor clinical outcome was defined as a mRS score of 3-6. Stroke lesion types based on MRI were classified into single vascular territory, multiple vascular territories, and multiple circulations. RESULTS: In total, 340 patients were enrolled, 84 (24.7%) of whom were diagnosed in nonneurology departments. Among the 84 consultations, 57 cases were symptomatic ischemic strokes, and 27 cases exhibited irrelevant acute ischemic lesions. With respect to the stroke subtype, other cause (10.7% vs 4.8%) and undetermined cause (42.9% vs 20.7%) were more common in the nonneurology department patients (p<0.0001). Acute ischemic strokes in multiple circulations were also more common in those from nonneurology departments (44.0% vs 11.0%, p<0.0001), along with higher high-sensitivity C-reactive protein levels. A poor clinical outcome was more common among patients in the nonneurology departments than among those in the neurology department (75.0% vs 27.5%, p<0.0001). CONCLUSIONS: Ischemic strokes from nonneurology departments tend to appear as nonlocalizing neurologic symptoms and spread in multiple circulations, and are associated with a worse outcome than those from neurology departments.
C-Reactive Protein ; Diagnosis ; Humans ; Infarction ; Magnetic Resonance Imaging ; National Institutes of Health (U.S.) ; Neurologic Manifestations ; Neurology ; Referral and Consultation ; Risk Factors ; Stroke*

Considerable progress has been made in treatments for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) over the last several decades. However, the present treatments do not show satisfactory efficacy or safety in a considerable proportion of patients, who experience relapse or disability progression despite receiving treatment and suffer from side effects, which can be severe. Improvements in the understanding of the pathophysiologies of MS and NMOSD have led to numerous therapeutic approaches being proposed and developed. Monoclonal antibodies (mAbs) are receiving increasing attention because of their specificity of action and likelihood of high efficacy with fewer side effects.Many mAbs have been evaluated, and some have been approved for MS or NMOSD treatment. This article reviews the use of mAbs for treating MS and NMOSD, including summarizing their mechanisms of action, efficacy, and safety profiles.

Descriptions of symptomatic focal dystonia caused by focal lesions of the central nervous system (CNS) are rare in the literature. We report a 9-year-old child who experienced sudden-onset left-hand dystonia for 6 months. Brain magnetic resonance imaging showed a mass lesion involving the putamen, globus pallidus, head of caudate, and the anterior limb of the internal capsule. Histopathological and immunocytochemical examinations of the mass revealed features characteristic of malignant germinoma. CNS germinoma in the basal ganglia is very rare. Combining previous reports in the literature with the anatomical and clinical presentation of our case suggests that this phenomenon results from disruption of the pathways within and adjacent to the basal ganglia.
Basal Ganglia* ; Brain ; Central Nervous System ; Child ; Dystonia* ; Dystonic Disorders ; Extremities ; Germinoma* ; Globus Pallidus ; Hand* ; Head ; Humans ; Internal Capsule ; Magnetic Resonance Imaging ; Putamen

Descriptions of symptomatic focal dystonia caused by focal lesions of the central nervous system (CNS) are rare in the literature. We report a 9-year-old child who experienced sudden-onset left-hand dystonia for 6 months. Brain magnetic resonance imaging showed a mass lesion involving the putamen, globus pallidus, head of caudate, and the anterior limb of the internal capsule. Histopathological and immunocytochemical examinations of the mass revealed features characteristic of malignant germinoma. CNS germinoma in the basal ganglia is very rare. Combining previous reports in the literature with the anatomical and clinical presentation of our case suggests that this phenomenon results from disruption of the pathways within and adjacent to the basal ganglia.
Basal Ganglia* ; Brain ; Central Nervous System ; Child ; Dystonia* ; Dystonic Disorders ; Extremities ; Germinoma* ; Globus Pallidus ; Hand* ; Head ; Humans ; Internal Capsule ; Magnetic Resonance Imaging ; Putamen

BACKGROUND AND PURPOSE: Different mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported in approximately 10% of cases of familial amyotrophic lateral sclerosis (ALS). The aim of this study was to analyze for mutations in the SOD1 gene and clinical characteristics in Korean family of ALS. METHODS: A subpopulation of the family reported here has been described previously. In the present study, we analyzed the SOD1 gene in the proband and his immediate family members, who were not reported on previously. Genomic DNA was isolated from the leukocytes of whole blood samples and the coding region of the SOD1 gene was analyzed by PCR and direct sequencing. RESULTS: The genetic alterations were a GGC-to-GTT transition at codon 10 in exon 1 and [IVS4+15_16insA; IVS4+42delG; IVS4+59_60insT] in intron 4. Patients with these mutations exhibit diverse clinical onset symptoms and acceleration of the age at onset in successive generations, which is called anticipation. CONCLUSIONS: We have described a family with familial ALS that showed autosomal-dominant inheritance and two distinct genetic alterations in Cu/Zn-SOD1. The affected family members had different phenotypes and anticipation.
Acceleration ; Amyotrophic Lateral Sclerosis* ; Clinical Coding ; Codon ; DNA ; Exons ; Family Characteristics ; Humans ; Introns ; Leukocytes ; Phenotype ; Polymerase Chain Reaction ; Population Characteristics* ; Superoxide Dismutase* ; Superoxides* ; Wills