With the introduction of interferon-β1b in 1993 as the first FDA-approved treatment for multiple sclerosis, the era of treatment of this incurable disease began, and its natural course was ...permanently changed. Currently, seven different treatments for patients with multiple sclerosis with different mechanisms of action and dissimilar side effect profiles exist. These medications include interferon-β1a intramuscular (Avonex), interferon-β1a subcutaneous (Rebif), interferon-β1b subcutaneous (Betaseron/Extavia), glatiramer acetate (Copaxone), natalizumab (Tysabri), fingolimod (Gilenya), teriflunomide (Aubagio), and mitoxantrone (Novantrone). In addition, a large number of clinical trials are being conducted to assess the safety and efficacy of various experimental agents in patients with multiple sclerosis, including alemtuzumab, dimethyl fumarate, laquinimod, rituximab, daclizumab, and cladribine. In this paper, the author presents a concise and comprehensive review of present and potential treatments for this incurable disease.
Multiple sclerosis (MS) is one of the most common chronic immune-mediated diseases of the human central nervous system and an important cause of non-traumatic neurologic disability among young ...population in several countries. Recent reports from East Asia, South East Asia and South Asia have proposed a low to moderate prevalence of MS in these countries.
A literature review search was carried out in December 2014 in Medline, Embase, Scopus and Cochrane library to recover original population-based studies on MS epidemiology in East Asia, South East Asia and South Asia countries published between January 1, 1950 and December 30, 2014. We intended search strategies using the key words: multiple sclerosis, prevalence, incidence and epidemiology. Based on our inclusion criteria, 68 epidemiologic studies were included in this systematic review.
The most extensively used diagnostic criteria in the studies were McDonald's criteria. Most studies were performed in a multi-center hospital setting. The female to male ratio varied and ranged from 0.7 in India to 9.0 in China. The mean age at disease onset ranged from the lowest age of 25.3 in Iran to the highest age of 46.4 in China. MS prevalence ranged from 0.77 in 100,000 populations in Hong Kong (1999) to 85.80 in 100,000 in Iran (2013).
Advances in MS registries around the globe allow nationwide population-based studies and will allow worldly comparisons between the prevalence and incidence in different regions that are provided to monitor estimation.
The blood-brain barrier (BBB) is a complex organization of cerebral endothelial cells (C EC), pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular ...macrophages. C ollectively these cells separate and form the compartments of the cerebral vascular space and the cerebral interstitium under normal conditions. Without the BBB, the ‘interior milieu’ of the central nervous system (CNS) would be flooded by humoral neurotransmitters and formed blood elements that upset normal C NS functions and lead to vascular/neural injury. Dysregulation of the BBB and transendo thelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in multiple sclerosis (MS) brains and parallel the release of inflammatory cytokines/chemokines. Mechanisms for breakdown of the BBB in MS are incompletely understood, but appear to involve direct effects of these cytokines/chemokines on endothelial regulation of BBB components, as well as indirect cytokine/chemokine-dependent leukocyte mediated injury.
Unique endothelial structural features of the BBB include highly organized endothelial tight junctions, the absence of class II major histocompatibility complex, abundant mitochondria and a highly developed transport system in C EC. Exposure of endothelium to proinflammatory cytokines (IFN-g, TNF-a and IL-1b) interrupts the BBB by disorganizing cell-cell junctions, decreases the brain solute barrier, enhances leukocyte endothelial adhesion and migration as well as increases expression of class II MHC and promotes shedding of endothelial ‘microparticles’ (EMP). In this review we examine interactions between cytokines/chemokines, activated leukocytes, adhesion molecules and activated C EC in the pathogenesis of BBB failure in MS.
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, ...options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia.
The methylation of arginine residues by protein arginine methyltransferases (PRMTs) is a type of post-translational modification which is important for numerous cellular processes, including mRNA ...splicing, DNA repair, signal transduction, protein interaction, and transport. PRMTs have been extensively associated with various pathologies, including cancer, inflammation, and immunity response. However, the role of PRMTs has not been well described in vascular and neurological function. Aberrant expression of PRMTs can alter its metabolic products, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). Increased ADMA levels are recognized as an independent risk factor for cardiovascular disease and mortality. Recent studies have provided considerable advances in the development of small-molecule inhibitors of PRMTs to study their function under normal and pathological states. In this review, we aim to elucidate the particular roles of PRMTs in vascular and neuronal function as a potential target for cardiovascular and neurological diseases.
A fatality in one multiple sclerosis (MS) patient due to acute idiopathic thrombocytopenic purpura (ITP) and a near fatality in another stimulated our interest in platelet function abnormalities in ...MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients.
In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation plasma platelet microparticles (PMP), P-selectin expression (CD62p), circulating platelet microaggragtes (PAg), as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured.
Compared to controls, PMP were significantly elevated in MS (p < 0.001) and CD62p expression was also markedly elevated (p < 0.001). Both are markers of platelet activation. Platelet-associated IgM, but not IgG, was marginally elevated in MS (p = 0.01). Protein S in MS patients did not differ significantly from normal values.
Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.
Macrophage/microglia (M∅) are the principal immune cells in the central nervous system (CNS) concomitant with inflammatory brain disease and play a significant role in the host defense against ...invading microorganisms. Astrocytes, as a significant component of the blood–brain barrier, behave as one of the immune effecter cells in the CNS as well. However, both cell types may play a dual role, amplifying the effects of inflammation and mediating cellular damage as well as protecting the CNS. Interactions of the immune system, M∅, and astrocytes result in altered production of neurotoxins and neurotrophins by these cells. These effects alter the neuronal structure and function during pathogenesis of HIV-1-associated dementia (HAD), Alzheimer disease (AD), and multiple sclerosis (MS). HAD primarily involves subcortical gray matter, and both HAD and MS affect sub-cortical white matter. AD is a cortical disease. The process of M∅ and astrocytes activation leading to neurotoxicity share similarities among the three diseases. Human Immunodeficiency Virus (HIV)-1-infected M∅ are involved in the pathogenesis of HAD and produce toxic molecules including cytokines, chemokines, and nitric oxide (NO). In AD, M∅s produce these molecules and are activated by β-amyloid proteins and related oligopeptides. Demyelination in MS involves M∅ that become lipid laden, spurred by several possible antigens. In these three diseases, cytokine/chemokine communications between M∅ and astrocytes occur and are involved in the balance of protective and destructive actions by these cells. This review describes the role of M∅ and astrocytes in the pathogenesis of these three progressive neurological diseases, examining both beneficent and deleterious effects in each disease.
Assessment of Mental Status Finney, Glen R; Minagar, Alireza; Heilman, Kenneth M
Neurologic clinics,
02/2016, Letnik:
34, Številka:
1
Journal Article
Recenzirano
Assessing the mental status of patients with a neurobehavioral disorder is a critical element in the diagnosis and treatment of these patients. This assessment should always be performed after the ...patient's history it taken and a general physical as well as a neurologic examination is completed. The mental status examination commences with observing the patient's appearance and level of consciousness. The examiner should also pay attention to patient's social behavior, emotional state and mood. There are 3 major means of assessing a patient's mental status. One type attempts to determine if the patient is demented and the severity of the dementia as it pertains to their ability to perform activities of daily living as well as instrumental activities. A second type of assessment utilizes what may be termed as "screening tests" or "omnibus tests". These brief tests are performed independent of the patient's history and examination. The two most frequently used screening tests are the Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The third means of assessing a patient's mental status is by using specific neuropsychological tests that focus on specific domains of cognition, such as frontal executive functions, attention, episodic verbal and visuospatial memory, declarative knowledge such as language (speech, reading and writing) and arithmetical, as well as visuospatial and perceptual abilities. These neurobehavioral, neuropsychiatric and neuropsychological assessments of patients with a cognitive decline and behavioral abnormalities should often be accompanied by laboratory tests, and neuroimaging that can help determine the underlying pathologic process so that effective therapeutic and management approaches can be provided.
Metastases to the dura and adjacent parenchyma occur in 1%-2% of patients with prostate cancer. Dural metastases manifest as subdural fluid collections and present as a chronic subdural hematoma. We ...present a patient with advanced prostate cancer who experienced a fall and a traumatic brain injury. Computer tomography (CT) of the brain revealed a bilateral subdural hematoma (SDH). During the follow-up examination, the patient's mental status declined, and a follow-up brain CT showed an expansion of the SDH. Brain MRI with contrast demonstrated dural lesions suspicious for metastasis to the dura. Histopathologic examination of the lesions confirmed metastatic prostate adenocarcinoma. While uncommon, leptomeningeal-dural metastatic lesions stemming from prostate adenocarcinoma should be suspected in patients with known prostate cancer who present with subdural collections. This is even more significant if the patient with prostatic adenocarcinoma has sustained a recent head injury and presents with a subdural hematoma on neuroimaging. Brain MRI provides more data towards the differential diagnosis of these lesions and should be an essential part of the diagnostic workup. Biopsy and histopathologic examination of these lesions are indicated in the diagnostic workup of these uncommon lesions.
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