Magnetic Resonance Imaging as a Major Milestone in Multiple Sclerosis Diagnosis and Treatment

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Magnetic resonance imaging (MRI) has played a unique role in the diagnosis and management of patients with MS. In recent years, there have been considerable changes in the diagnostic criteria for MS as MRI-based studies have demonstrated their power in the earlier and more accurate diagnosis of the disease. Moreover, MRI metrics have become key supportive outcome measures for evaluating the efficacy of experimental treatments in randomized controlled trials. MRI can also be used as a prognostic tool in patients with clinically isolated syndrome (CIS). Conventional MR techniques including proton density, T1/T2-weighted images, and FLAIR sequences are now accepted in standard protocols for diagnostic and treatment outcome measures in clinical trials for MS. Radiological features may show a similarity between radiologically isolated syndrome and MS. Approximately two-thirds of individuals with RIS exhibit radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. However, a current challenge in the global application of established criteria for RIS involves the accurate classification of subjects with incidentally identified anomalies that are highly characteristic of MS, in comparison to those categorized in medical parlance as possessing "unidentified bright objects" or nonspecific T2-hyperintensities, which are commonly identified in patients with migraine headache who fulfill the spatial dissemination requirements for MS. The need for systematically acquired data for improvements in the classification of radiologically isolated syndrome (RIS) and the generation of risk algorithms are critically important, providing a basis for scientifically supported management and most importantly, minimizing the number of improperly classified subjects exposed to unnecessary medical testing, MS treatments, and psychological harm. In addition, brain atrophy is a common finding that can now be quantitatively assessed by MR volumetric measures. Further, integrated strategies that combine MRI and clinical markers in scoring systems have provided a potentially useful approach for the management of patients with MS.Wo

Evaluating Treatment Decision for Multiple Sclerosis

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Steps in the Pathogenesis of Multiple Sclerosis - I: From Neuroinflammation to Neurodegeneration

Background: Inflammation has been described as a deleterious factor in MS immunopathogenesis for a long time. However, recent studies have proved the neuronal protective and efficacious effects of inflammation. Inflammation in the brain is a double-edged process that may be beneficial in promoting homeostasis and repair, but can also result in tissue injury through the damaging potential of inflammatory mediators. Control mechanisms that minimize the extent of the inflammatory reaction are necessary in order to preserve brain architecture and restore function. The end result of the inflammatory process, neurotoxicity and/or neuroprotection, is a function of the fine balance between the two cellular systems and of the complex signaling relationships between anti-inflammatory neuroprotective factors. In central nervous system inflammation the extent of tissue injury depends on both native and adaptive elements of the immune system. Besides, inflammation is not limited with the invasion of exogeneus cells infiltrating from the blood brain barrier. Astrocytes and microglial cells as being endogeneous also play an important role in the process. Secondary inflammatory mediators from these cells trigger the unique local inflammation of central nervous system. In the active MS plaques distinct cytokines and chemokines have been determined. C o n c l u s i o n: Inflammation has different aspects and some proof of beneficial roles can be summarized: Before the clinical signs of /during the experimental allergic encephalomyelitis (EAE) the presence of IFN-g h a s been shown as a limitting factor for the progression, the delivery of anti- I F N -g monoclonal antibodies have increased the morbidity in EAE. CD4+ T cells stimulate microglial cells to secrete some mediators as interleukin E2 that can supress IL-12 and the same cells can also secrete neruprotective factors as brain derived neurotrophic factor. Another group of cells, macrophages trigger remyelinization by clearing myelin debris. This review discusses about the contradictory effects of inflammation on the immunopathogenesis of multiple sclerosis. It outlines the cells responsible for the inflammatory cascade, both beneficial and detrimental effects of inflammation on myelin and axonal integrity and additional relation for demyelination and axonal transsection

The Effect of Walking Distance on EDSS Score in Patients with Multiple Sclerosis

OBJECTIVE: This study aimed first to identify the range of the Expanded Disability Status Scale (EDSS) score by comparing the actual walking distance and the estimated walking distance of multiple sclerosis (MS) patients, and second, to investigate the effect of fatigue on walking distance. METHODS: Thirty MS patients and 20 age -and gender- matched healthy volunteers were included in the study. MS patients were divided into two groups according to the EDSS score. Fatigue was measured using the Fatigue Severity Scale (FSS) and motor fatigue was measured using the 200 meter walking test. The increase in muscle tone was evaluated by Modified Ashworth Scale. The first group of MS patients and healthy control group patients were asked to estimate the distance they can walk without rest within six minutes. Then, their actual walking distance was measured for six minutes. The second group of MS patients was asked to estimate their most probable walking distance without rest; then, the actual walking distance of the patients was measured. RESULTS: In terms of FSS values, fatigue severity was different in the two MS groups (p 0.05), the second MS group’s estimated and actual walking distances were significantly different (p< 0.05). A negative correlation was found between FSS scores and estimated walking distance in the second MS group (p< 0.05). A negative correlation was present between motor fatigue and actual walking distance only in the second MS group (p< 0.05). CONCLUSION: EDSS evaluation is more reliable in patients with low level disability. The accuracy issues arise in patients with EDSS scores of 4-5. Additionally, there is an important correlation between motor fatigue and walking distance in these patients. For motor fatigue, spasticity is an important determinant

Steps in Multiple Sclerosis Pathogenesis - II: The Role of Biological Markers, Sodium Channels and Glutamate in Neurodegeneration

Scientific background: Neurodegeneration following inflammatory in- jury is considered to be a pathological correlate of irreversible disability in patients with multiple sclerosis (MS). The presence of amyloid precur- sor protein in active lesions, oxidative injury of mitochondrial DNA, dis/inactivation of mitochondrial enzymes, loss of axonal density in nor- mal appearing white matter, reduction of N-acetylaspartate (NAA)/cre- atinin ratio in magnetic resonance spectroscopy (MRS) and the correla- tion between reduced NAA levels and disability have been determined as evidences of neurodegeneration in MS. In the disease immunopatho- genesis some biological indicators of axonal transsection as NAA, ac- tin, tubulin, L-neurofilaments, anti-axolemma IgG, antigangliozide anti- bodies, glial fibrillary acid protein, S-100 protein, nitric oxide, neuronal specific enolase, 14-3-3 protein, apoprotein E have been described and put in association with the clinicial status. The description of axonal transsection which is a main cause of disabi- lity has been made in the very early times when the first histopatholo- gic signs of multiple sclerosis were discovered. Although it has a long past, the role of neurodegenerative mechanisms in the axonal transsec- tion has been recently described. Genetic factors, excitotoxicity, apop- tosis, depletion of growth factors and energy, inducible demyelination are the other mechanisms that cause neurodegeneration. Recent studies have shown that glutamate excitotoxicity may be a com- ponent in the pathogenesis of MS. Glutamate transporters determine the levels of extracellular glutamate and are essential to prevent excitotoxicity. In MS, the evident association between insidious and prolonged microglial activation and glutamate excitotoxicity has been emphasized and in addition glutamate excitotoxicity is considered to be responsible due to progressive loss of oligodendrocytes (OLG). Excitotoxicity in OLGs begins as Ca + + influx via AMPA/kainat receptors. The number of AMPA re- ceptors increased on postsynaptic membrane and apoptotic cellular death occur because of prolonged activation of these receptors. Proinflamma- tory cytokines such as interlukine-1 and tumor necrosis-· as increasing receptor expression on OLGs cause to be prone to excitotoxic death. The gradual loss of axons is thought to underlie irreversible clinical defi- cits in this disease. The precise mechanisms of axonopathy are poorly understood, but likely involve excess accumulation of Ca ions. In healthy fibers, ATP-dependent pumps support homeostasis of ionic gradients. When energy supply is limited, either due to inadequate delivery (e.g., ischemia, mitochondrial dysfunction) and/or excessive utilization (e.g., conduction along demyelinated axons), ion gradients break down, unleashing a variety of aberrant cascades, ultimately leading to Ca overload. During Na pump dysfunction, Na can enter axons through non-inactivating Na channels, promoting axonal Na overload. This will gate voltage-sensitive Ca channels and stimulate reverse Na-Ca exchan- ge, leading to further Ca entry. Energy failure will also promote Ca release from intracellular stores. Also, after demyelination a new orga- nisation of different types of sodium channels has been shown to ap- pear on axons and inflammatory cells. In this manuscript the role of voltage-gated sodium channels and glu- tamate excitotoxicity, and interactions of glutamate with receptors and cytokines on the immunopathogenesis of multiple sclerosis are revie- wed and discusse

Acute Disseminated Encephalomyelitis After Oral Therapy With Herbal Extracts: A Case Report

Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. Case Report: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findings, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse methylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. Conclusion: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions.WoSScopu

Progressive Onset Multiple Sclerosis: Demographic, Clinical And Laboratory Characteristics Of Patients With And Without Relapses In The Course

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Comparing Routine Neurorehabilitation Program With Trunk Exercises Based On Bobath Concept In Multiple Sclerosis: Pilot Study

This study compared trunk exercises based on the Bobath concept with routine neurorehabilitation approaches in multiple sclerosis (MS). Bobath and routine neurorehabilitation exercises groups were evaluated. MS cases were divided into two groups. Both groups joined a 3 d/wk rehabilitation program for 8 wk. The experimental group perfolined trunk exercises based on the Bobath concept, and the control group performed routine neurorehabilitation exercises. Additionally, both groups performed balance and coordination exercises. All patients were evaluated with the Trunk Impairment Scale (TIS), Berg Balance Scale (BBS), International Cooperative Ataxia Rating Scale (ICARS), and Multiple Sclerosis Functional Composite (MSFC) before and after the physiotherapy program. In group analysis, TIS, BBS, ICARS, and MSFC scores and strength of abdominal muscles were significantly different after treatment in both groups (p 0.05). Although trunk exercises based on the Bobath concept are rarely applied in MS rehabilitation, the results of this study show that they are as effective as routine neurorehabilitation exercises. Therefore, trunk exercises based on the Bobath concept can be beneficial in MS rehabilitation programs.WoSScopu