Displaying publications 21 - 40 of 50 in total

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  1. Paudel YN, Angelopoulou E, Piperi C, Gnatkovsky V, Othman I, Shaikh MF
    Curr Neuropharmacol, 2020;18(11):1126-1137.
    PMID: 32310049 DOI: 10.2174/1570159X18666200420125017
    Epilepsy is a devastating neurological condition characterized by long-term tendency to generate unprovoked seizures, affecting around 1-2 % of the population worldwide. Epilepsy is a serious health concern which often associates with other neurobehavioral comorbidities that further worsen disease conditions. Despite tremendous research, the mainstream anti-epileptic drugs (AEDs) exert only symptomatic relief leading to 30% of untreatable patients. This reflects the complexity of the disease pathogenesis and urges the precise understanding of underlying mechanisms in order to explore novel therapeutic strategies that might alter the disease progression as well as minimize the epilepsy-associated comorbidities. Unfortunately, the development of novel AEDs might be a difficult process engaging huge funds, tremendous scientific efforts and stringent regulatory compliance with a possible chance of end-stage drug failure. Hence, an alternate strategy is drug repurposing, where anti-epileptic effects are elicited from drugs that are already used to treat non-epileptic disorders. Herein, we provide evidence of the anti-epileptic effects of Fingolimod (FTY720), a modulator of sphingosine-1-phosphate (S1P) receptor, USFDA approved already for Relapsing-Remitting Multiple Sclerosis (RRMS). Emerging experimental findings suggest that Fingolimod treatment exerts disease-modifying anti-epileptic effects based on its anti-neuroinflammatory properties, potent neuroprotection, anti-gliotic effects, myelin protection, reduction of mTOR signaling pathway and activation of microglia and astrocytes. We further discuss the underlying molecular crosstalk associated with the anti-epileptic effects of Fingolimod and provide evidence for repurposing Fingolimod to overcome the limitations of current AEDs.
    Matched MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
  2. Rovina K, Siddiquee S, Shaarani SM
    Front Microbiol, 2016;7:798.
    PMID: 27303385 DOI: 10.3389/fmicb.2016.00798
    Allura Red AC (E129) is an azo dye that widely used in drinks, juices, bakery, meat, and sweets products. High consumption of Allura Red has claimed an adverse effects of human health including allergies, food intolerance, cancer, multiple sclerosis, attention deficit hyperactivity disorder, brain damage, nausea, cardiac disease and asthma due to the reaction of aromatic azo compounds (R = R' = aromatic). Several countries have banned and strictly controlled the uses of Allura Red in food and beverage products. This review paper is critically summarized on the available analytical and advanced methods for determination of Allura Red and also concisely discussed on the acceptable daily intake, toxicology and extraction methods.
    Matched MeSH terms: Multiple Sclerosis
  3. Kuan TLT, Amini F, Seghayat MS
    Iran J Basic Med Sci, 2017 Jul;20(7):729-738.
    PMID: 28852436 DOI: 10.22038/IJBMS.2017.9000
    Multiple sclerosis is a debilitating disease of the central nervous system. It affects people of all ages but is more prevalent among 20-40 year olds. Patients with MS can be presented with potentially any neurological symptom depending on the location of the lesion. A quarter of patients with MS suffer from bilateral lower limb spasticity among other symptoms. These devastating effects can be detrimental to the patient's quality of life. Hematopoietic stem cells (HSCs) have been used as a treatment for MS over the past 2 decades but their safety and efficacy has are undetermined. The objective of this study is to evaluate the feasibility and toxicity of autologous HSCs transplantation in MS. A literature search was done from 1997 to 2016 using different keywords. A total of 9 articles, which met the inclusion and exclusion criteria, were included in this review. The type of conditioning regimen and technique of stem cell mobilization are summarized and compared in this study. All studies reported high-dose immunosuppressive therapy with autologous HSCs transplantation being an effective treatment option for severe cases of multiple sclerosis. Fever, sepsis, and immunosuppression side effects were the most observed adverse effects that were reported in the selected studies. HSCs is a feasible treatment for patients with MS; nevertheless the safety is still a concern due to chemo toxicity.
    Matched MeSH terms: Multiple Sclerosis
  4. Zahiri N, Abollahi I, Nabavi SM, Ehsani F, Arab AM, Shaw I, et al.
    Malays J Med Sci, 2017 Mar;24(1):69-80.
    PMID: 28381930 DOI: 10.21315/mjms2017.24.1.8
    BACKGROUND: Multiple sclerosis (MS) is the most widespread disabling neurological condition in young adults around the world. The purpose of this study was to investigate the impact of explicit information (EI) on motor-sequence learning in MS patients.

    METHODS: Thirty patients with relapsing-remitting MS (RRMS), age: 29.5 (SD = 5.6) years and 30 healthy gender-, age-, and education-matched control group participants, age: 28.8 (SD = 6.0) years, were recruited for this study. The participants in the healthy group were then randomly assigned into an EI (n = 15) group and a no-EI (n = 15) group. Similarly, the participants in the control group were then randomly assigned into EI (n = 15) and no-EI (n = 15) groups. The participants performed a serial reaction time (SRT) task and reaction times. A retention test was performed after 48 hours.

    RESULTS: All participants reduced their reaction times across acquisition (MS group: 46.4 (SD = 3.3) minutes, P < 0.001, and healthy group: 39.4 (SD = 3.3) minutes, P < 0.001). The findings for the within-participants effect of repeated measures of time were significant (F(5.06, 283.7) = 71.33. P < 0.001). These results indicate that the interaction between group and time was significant (F(5.06, 283.7) = 6.44. P < 0.001), which indicated that the reaction time in both groups was significantly changed between the MS and healthy groups across times (B1 to B10). The main effect of the group (MS and healthy) (F(1, 56) = 22.78. P < 0.001) and also the main effect of no-EI vs EI (F(1, 56) = 4.71. P < 0.001) were significant.

    CONCLUSION: This study demonstrated that that RRMS patients are capable of learning new skills, but the provision of EI prior to physical practice is deleterious to implicit learning. It is sufficient to educate MS patients on the aim and general content of the training and only to provide feedback at the end of the rehabilitative session.

    Matched MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
  5. Razazian N, Kazeminia M, Moayedi H, Daneshkhah A, Shohaimi S, Mohammadi M, et al.
    BMC Neurol, 2020 Mar 13;20(1):93.
    PMID: 32169035 DOI: 10.1186/s12883-020-01654-y
    BACKGROUND: Despite many benefits of the physical activity on physical and mental health of patients with Multiple Sclerosis (MS), the activity level in these patients is still very limited, and they continue to suffer from impairment in functioning ability. The main aim of this study is thus to closely examine exercise's effect on fatigue of patients with MS worldwide, with particular interest on Iran based on a comprehensive systematic review and meta-analysis.

    METHODS: The studies used in this systematic review were selected from the articles published from 1996 to 2019, in national and international databases including SID, Magiran, Iranmedex, Irandoc, Google Scholar, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant ones were selected based on some plausible keywords to the aim of this study. Heterogeneity index between studies was determined using Cochran's test and I2. Due to heterogeneity in studies, the random effects model was used to estimate standardized mean difference.

    RESULTS: From the systematic review, a meta-analysis was performed on 31 articles which were fulfilled the inclusion criteria. The sample including of 714 subjects was selected from the intervention group, and almost the same sample size of 720 individuals were selected in the control group. Based on the results derived from this meta-analysis, the standardized mean difference between the intervention group before and after the intervention was respectively estimated to be 23.8 ± 6.2 and 16.9 ± 3.2, which indicates that the physical exercise reduces fatigue in patients with MS.

    CONCLUSION: The results of this study extracted from a detailed meta-analysis reveal and confirm that physical exercise significantly reduces fatigue in patients with MS. As a results, a regular exercise program is strongly recommended to be part of a rehabilitation program for these patients.

    Matched MeSH terms: Multiple Sclerosis/complications; Multiple Sclerosis/rehabilitation*
  6. Viswanathan S, Botross N, Rusli BN, Riad A
    Mult Scler Relat Disord, 2016 Nov;10:112-115.
    PMID: 27919476 DOI: 10.1016/j.msard.2016.10.001
    Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients.
    Matched MeSH terms: Multiple Sclerosis/cerebrospinal fluid
  7. Cheong WL, Mohan D, Warren N, Reidpath DD
    Mult Scler Relat Disord, 2019 Oct;35:86-91.
    PMID: 31357123 DOI: 10.1016/j.msard.2019.07.009
    BACKGROUND: Despite the global consensus on the importance of palliative care for patients with multiple sclerosis (MS), many patients in developing countries do not receive palliative care. Improving access to palliative care for MS requires a contextual understanding of how palliative care is perceived by patients and health professionals, the existing care pathways, and barriers to the provision of palliative care.

    OBJECTIVE: This study aims to examine and contrast the perceptions of MS patients, neurologists, and palliative care physicians towards providing palliative care for patients with MS in Malaysia.

    METHODS: 12 MS patients, 5 neurologists, and 5 palliative care physicians participated in this qualitative study. Each participant took part in a semi-structured interview. The interviews were transcribed verbatim, and analysed using an iterative thematic analysis approach.

    RESULTS: Patients and neurologists mostly associated palliative care with the end-of-life and struggled to understand the need for palliative care in MS. Another barrier was the lack of understanding about the palliative care needs of MS patients. Palliative care physicians also identified the scarcity of resources and their lack of experience with MS as barriers. The current referral-based care pathway itself was found to be a barrier to the provision of palliative care.

    CONCLUSIONS: MS patients in Malaysia face several barriers in accessing palliative care. Overcoming these barriers will require improving the shared understanding of palliative care and its role in MS. The existing care pathway also needs to be reformed to ensure that it improves access to palliative care for MS patients.

    Matched MeSH terms: Multiple Sclerosis/therapy*
  8. Cheong WL, Mohan D, Warren N, Reidpath DD
    Disabil Rehabil, 2021 07;43(15):2184-2190.
    PMID: 31769306 DOI: 10.1080/09638288.2019.1695000
    BACKGROUND: The needs of patients with multiple sclerosis have been well-studied in high-income, high-prevalence countries but few studies have been based in low- and middle-income countries where resources are relatively scarce. As such, little is known about the needs of patients living in these countries.

    OBJECTIVE: The study seeks to develop an understanding of the needs of patients with multiple sclerosis living in Malaysia in order to generate insights and contribute to a global database of patients' experience.

    METHOD: 12 patients with multiple sclerosis participated in this qualitative study and took part in a semi-structured interview. The interviews were transcribed and analysed using an iterative thematic analysis approach.

    RESULTS: The experiences, challenges and needs of the patients were reported. Five themes were developed (Daily living, Financial, Emotional and psychological, Healthcare, and Family). These predominantly revolved around the struggles of coping and adapting to the symptoms and disabilities imposed by multiple sclerosis, their heavy reliance on personal finances to cope with the increased costs of living for themselves and their families, as well as the limited healthcare services and treatments available to help them to manage the physical and emotional symptoms of multiple sclerosis.

    CONCLUSION: Patients with multiple sclerosis in Malaysia have complex needs that are neglected due perceived lack of importance of the disease and the poor understanding of multiple sclerosis in general. Patients rely heavily on their finances to improve their quality of life. This perpetuates health inequities and reform of the national health financing system is needed to provide patients with the healthcare and support they need.Implications for rehabilitationPatients with multiple sclerosis in Malaysia prioritize being able to cope and adapt to their disabilities in order to continue performing their activities of daily living.There is a need to increase the availability and accessibility of healthcare professionals that are experienced with the management of multiple sclerosis.Healthcare professionals need to improve their understanding of the patients' needs and what they consider to be important in order to provide therapy that is effective and relevant.Patients also require financial support to help them with the increased costs of living associated with MS as well as the costs of healthcare services such as physiotherapy and rehabilitation.

    Matched MeSH terms: Multiple Sclerosis*
  9. Gough N, Brkan L, Subramaniam P, Chiuccariello L, De Petrillo A, Mulsant BH, et al.
    PLoS One, 2020;15(2):e0223029.
    PMID: 32092069 DOI: 10.1371/journal.pone.0223029
    With technological advancements and an aging population, there is growing interest in delivering interventions at home. Transcranial Direct Current Stimulation (tDCS) and Cognitive Remediation (CR) as well as Cognitive Training (CT) have been widely studied, but mainly in laboratories or hospitals. Thus, the objectives of this review are to examine feasibility and the interventions components to support the domiciliary administration of tDCS and CR. We performed a systematic search of electronic databases, websites and reference lists of included articles from the first date available until October 31, 2018. Articles included had to meet the following criteria: original work published in English using human subjects, majority of tDCS or CR intervention administered remotely. A total of 39 studies were identified (16 tDCS, 23 CR/CT, 5 using both tDCS & CT). Four studies were single case studies and two were multiple case studies. The remaining 33 studies had a range of 9-135 participants. Five tDCS and nine CR/CT studies were double blind randomized controlled trials. Most studies focused on schizophrenia (8/39) and multiple sclerosis (8/39). Literature examined suggests the feasibility of delivering tDCS or CR/CT remotely with the support of information and communication technologies.
    Matched MeSH terms: Multiple Sclerosis/therapy
  10. Paudel YN, Angelopoulou E, C BK, Piperi C, Othman I
    Life Sci, 2019 Dec 01;238:116924.
    PMID: 31606383 DOI: 10.1016/j.lfs.2019.116924
    Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease with distinctive features of focal demyelination, axonal loss, activation of glial cells, and immune cells infiltration. The precise molecular mechanism underlying the disease progression remains enigmatic despite of the rapid progression on experimental and clinical MS research. The focus of MS therapy relies on the repression of the pathogenic autoimmune response without compromising an adaptive immune response. High mobility group box-1 (HMGB1) protein is a ubiquitous nuclear protein driving pro-inflammatory responses as well as targeting innate immune signaling that initiates and mediates autoimmunity as well as sterile injury. A considerable amount of experimental and human studies suggests the contribution of HMGB1 in the pathogenesis of MS/experimental autoimmune encephalitis (EAE). In this regard, HMGB1 protein has gained increased attention, as an emerging possible therapeutic target against MS. This is more strengthened by the promising therapeutic outcome demonstrated by HMGB1 neutralizing agents in the experimental EAE model. Herein, we attempt to shed more light on the molecular crosstalk of HMGB1 protein in the pathogenesis of MS/EAE suggesting that HMGB1 blockade could impede the pro-inflammatory loop that drives MS autoimmunity.
    Matched MeSH terms: Multiple Sclerosis/drug therapy*; Multiple Sclerosis/metabolism; Multiple Sclerosis/pathology
  11. Viswanathan S, Rose N, Arip M, Chai CH, Law WC, Sim R, et al.
    Mult Scler Relat Disord, 2018 Oct;25:300-308.
    PMID: 30172173 DOI: 10.1016/j.msard.2018.07.003
    We performed a retrospective observational analytical study looking at the frequencies and characteristics of multiple sclerosis(MS) and neuromyelitis optica spectrum disorders(NMOSD) in consecutive patients with idiopathic inflammatory demyelinating disease (IIDDs) attending three centers (2009-2017). Of 523 patients with IIDDs, there were 173 patients with NMOSD and 230 patients with MS. The percentage of NMOSD: IIDDs was 33%. The percentage of NMOSD:Total MS and NMOSD cohort was 43%. Of 141 seropositive NMOSD patients, 134(95%) were from the three main ethnic groups. The percentage of seropositive NMOSD to IIDDs and to combined MS and NMOSD was 26.9% and 35% respectively. Ratios of MS to NMOSD were nearly equal at 1.3 to 1.0, reinforcing the high ratio of NMOSD to MS in Asia. Nearly half of the Chinese cohort were seropositive ie; 71/141 (50%) with the remainder being Malays; 56/141 (39.7%) and Indians; 7/141 (5%). Amongst the other indigenous groups seropositivity was seen in 2 each of Iban, Bajau, Kadazan descent as well as one of Bidayuh origin. Comparatively, seropositivity in NMOSD is commoner amongst the Chinese compared to the Malays (p ≤ 0.005) and Indians, p ≤ 0.05 with ratios as high as 10:1. In the MS group of 230 subjects, 123(53.5%) were Malays (ratio of MS:NMOSD of 2:1), 41(17.8%) were Chinese, (ratio of MS:NMOSD of 0.5:1.0) and 54 (23.5%)were Indians (ratios of MS:NMOSD of 5:1 amongst the Indians). The remainder from East Malaysia were made up of 2 each of Kadazans, Ibans and Bajaus including 3 each of Bidayuh and Eurasian descent. Comparatively, in the NMOSD and MS cohorts a female preponderance was noted more so amongst Chinese NMOSD patients, with rare familial occurrence in both but more in Malay MS/NMOSD patients. This study also highlighted some of the inter-ethnic differences in presentation of MS and NMOSD amongst the 3 main ethnic races in Malaysia and confirms indigenous races having MS/NMOSD which needs further research. It also reviewed current literature on similar inter-ethnic differences world wide. To conclude, MS and NMOSD are the commonest demyelinating diseases seen in Malaysia with interesting inter-ethnic differences and similarities.
    Matched MeSH terms: Multiple Sclerosis/ethnology*; Multiple Sclerosis/epidemiology*
  12. Thumboo J, Seah A, Tan CT, Singhal BS, Ong B
    Ann Acad Med Singap, 2011 Feb;40(2):67-73.
    PMID: 21468459
    INTRODUCTION: The Multiple Sclerosis International Quality of Life questionnaire (MusiQoL) is a self-administered, multi-dimensional, patient-based health-related quality of life (HRQoL) instrument. With increasing prevalence of multiple sclerosis (MS) in Asian countries, a valid tool to assess HRQoL in those patients is needed. The aim of this study was to evaluate patient acceptability, content validity and psychometric properties of an Asian version of the English MusiQoL in Singapore, Malaysia and India.

    MATERIALS AND METHODS: English speaking patients older than 18 years of age with a defi nite diagnosis of MS were included. The self-administered survey material included the adapted HRQoL questionnaire, a validated generic HRQoL questionnaire: the short-form 36 (SF-36), as well as a checklist of 14 symptoms. We assessed the internal and external validity of the adapted MusiQoL.

    RESULTS: A total of 81 patients with MS were included in the study. The questionnaire was generally well accepted. In the samples from Malaysia and Singapore, all scales exhibited good internal consistency (Cronbach's alpha >0.70). Correlation to SF-36 was generally good, demonstrating high construct validity (P <0.001) in some aspects of the MusiQoL.

    CONCLUSION: The Asian adaptation of the English version of the MusiQoL in evaluating HRQoL seems to be a valid, reliable tool with adequate patient acceptability and internal consistency.

    Matched MeSH terms: Multiple Sclerosis/drug therapy; Multiple Sclerosis/psychology*
  13. Seah, B.H.A., Tow, S.L.C., Ong, K.C.B. Ong, Yang, C.C., Tsai, C.P., Lee, K.H., et al.
    Neurology Asia, 2017;22(4):341-348.
    MyJurnal
    Optic neuritis, which may be a precursor to multiple sclerosis (MS), is an uncommon disease in
    Asian patients. The Asian Collaborative Longitudinal Optic Neuritis Epidemiology (ACLONE) is
    an observational cohort study that assessed the risk of recurrent optic neuritis and/or progression
    of further neurologic events, either MS or neuromyelitis optica (NMO) in Asian patients with firstever
    optic neuritis. Secondary aims were to study the presenting characteristics and visual outcome,
    and to identify risk factors for development of either MS or NMO. A total of 112 patients (25 men
    and 87 women) aged from 12 to 61 years were recruited from Singapore, Taiwan, South Korea and
    Malaysia. Of these, 94 (84%) had unilateral optic neuritis, with the right eye involved in 45 patients
    and the left eye in 49 patients and the remaining 18 (16%) had bilateral optic neuritis. Follow up
    data was available for 104 patients, and patients were followed for a median duration of 25.9 months.
    Of these patients, 6 patients were adjudicated to have reached the primary endpoint (composite of
    MS/NMO and optic neuritis): 3 patients with recurrent optic neuritis also subsequently experienced
    neurologic symptoms, and 3 patients without recurrent eye involvement had neurologic symptoms.
    Only one patient was considered to have prototypical MS, the other 5 were diagnosed with NMO,
    all with subsequent antibody confirmation. Optic neuritis in Asian patients has significantly different
    presenting characteristics from the classic description. However, in the majority of the patients it is
    usually a benign disease, with good visual outcome and no further events.
    Matched MeSH terms: Multiple Sclerosis
  14. Vijayasingham L, Mairami FF
    PMID: 30050385 DOI: 10.2147/DNND.S131729
    Patients with multiple sclerosis tend to report higher levels of work difficulties and negative outcomes, such as voluntary and involuntary work termination and reduced work participation. In this article, we discuss the complex interactions of disease, personal coping strategies, and social and structural factors that contribute to their work experiences and outcomes. An overview of the coping strategies and actions that leverage personal and context-level factors and dynamics is also provided to support the overall goal of continued work in patients with MS.
    Matched MeSH terms: Multiple Sclerosis
  15. Tan CT, Leong S
    Singapore Med J, 1992 Dec;33(6):575-80.
    PMID: 1488664
    A study of visual evoked potential (VEP), brainstem evoked potential (BAEP) and median nerve somatosensory evoked potential (SSEP) in 26 Malaysian patients with clinically definite Multiple Sclerosis (MS). This study showed an overall high rate of abnormality, with 85% of patients for VEP, 31% for BAEP and 65% for median nerve SSEP. The rate of abnormality was particularly high for patients who were symptomatic, reaching 100% of patients for VEP, 50% of patients in BAEP, 83% of nerves for median nerve SSEP. The rate of abnormality among those who were asymptomatic was lower, varying from 32% of eyes in VEP, 27% of patients in BAEP and 31% of nerves in median nerve SSEP. Three out of 10 patients with optic spinal form of MS have abnormal BAEP. These show the usefulness of the evoked potential studies in confirming the clinical lesions as well as demonstrating subclinical involvement. The rate of abnormal evoked responses for the asymptomatic patients in this study is generally lower than that published elsewhere.
    Matched MeSH terms: Multiple Sclerosis/physiopathology*
  16. Purohit B, Ganewatte E, Kollias SS
    Malays J Med Sci, 2016 Sep;23(5):91-95.
    PMID: 27904430
    Multiple sclerosis (MS) patients treated with natalizumab often face the uncommon but severe complication of developing progressive multifocal leukoencephalopathy (PML). PML may be further complicated by immune reconstitution inflammatory syndrome (IRIS) after the removal of the drug. Since both PML and IRIS are associated with high morbidity and mortality rates, early clinical and radiological diagnosis of these complications is of paramount importance. Here, we report a case of an adult male patient who was diagnosed with PML after receiving natalizumab therapy for 6 years for the treatment of MS. Upon cessation of natalizumab, he presented with a paradoxical worsening of clinical and radiological findings consistent with an inflammatory brain injury due to IRIS. He was treated with high dose corticosteroid therapy followed by a gradual improvement in clinical and imaging findings. This article illustrates the magnetic resonance imaging (MRI) features of natalizumab-associated PML-IRIS, along with a brief overview of its clinical features, complications and management strategies.
    Matched MeSH terms: Multiple Sclerosis
  17. Malko P, Syed Mortadza SA, McWilliam J, Jiang LH
    Front Pharmacol, 2019;10:239.
    PMID: 30914955 DOI: 10.3389/fphar.2019.00239
    Microglial cells in the central nervous system (CNS) are crucial in maintaining a healthy environment for neurons to function properly. However, aberrant microglial cell activation can lead to excessive generation of neurotoxic proinflammatory mediators and neuroinflammation, which represents a contributing factor in a wide spectrum of CNS pathologies, including ischemic stroke, traumatic brain damage, Alzheimer's disease, Parkinson's disease, multiple sclerosis, psychiatric disorders, autism spectrum disorders, and chronic neuropathic pain. Oxidative stress is a salient and common feature of these conditions and has been strongly implicated in microglial cell activation and neuroinflammation. The transient receptor potential melastatin-related 2 (TRPM2) channel, an oxidative stress-sensitive calcium-permeable cationic channel, is highly expressed in microglial cells. In this review, we examine the recent studies that provide evidence to support an important role for the TRPM2 channel, particularly TRPM2-mediated Ca2+ signaling, in mediating microglial cell activation, generation of proinflammatory mediators and neuroinflammation, which are of relevance to CNS pathologies. These findings lead to a growing interest in the TRPM2 channel, a new player in neuroinflammation, as a novel therapeutic target for CNS diseases.
    Matched MeSH terms: Multiple Sclerosis
  18. Espiritu AI, Leochico CFD, Separa KJNJ, Jamora RDG
    Mult Scler Relat Disord, 2020 Feb;38:101862.
    PMID: 31778926 DOI: 10.1016/j.msard.2019.101862
    BACKGROUND: Scientific productivity in the Southeast Asian (SEA) region in the field of multiple sclerosis and neuromyelitis optica spectrum disorder (MS/ NMOSD) was hypothesized to be low in magnitude. The aim of this study was to determine and compare MS/ NMOSD research outputs among the SEA countries in terms of established bibliometric indices. The association between these productivity indices and relevant country-specific socioeconomic factors was also determined.

    METHODS: A systematic review was conducted to include all relevant published MS/ NMOSD studies in the SEA indexed in MEDLINE, Embase, Scopus and CENTRAL from the inception of these databases to August 1, 2019. Quantity of research productivity was measured in terms of the total published documents. Quality of research impact was evaluated by assessing the study designs of the published reports, publications in journals with impact factor (IF) and PlumX Metrics (citations, usage, captures, mentions and social medias). Population size, gross domestic product (GDP) per capita, percentage (%) of GDP allocated to research and development (R&D), and the total number of neurologists reported in each country were obtained from reliable published data.

    RESULTS: Out of 3,547 articles identified, only 142 articles fulfilled the eligibility criteria; therefore, the total number of publications in the SEA region related to MS/ NMOSD was deemed low in quantity. Most studies were cross-sectional and case reports/ series; hence, most studies offered low level of evidence. Since the aggregate scores in citations, usage, captures, mentions, and social medias in PlumX Metrics and publications in journals with IF were low, the overall quality of the published articles was considered low. Thailand (57 articles), Malaysia (40) and Singapore (29) contributed to the majority of publications on the topic-. GDP per capita was statistically correlated with usage. Percent GDP for R&D was positively correlated with total publications, usage, captures and social mediaindices.

    CONCLUSION: In conclusion, the scientific impact of MS/ NMOSD in the SEA was considered low in quantity and quality. This study must encourage researchers in the SEA to produce greater volumes of high-quality publications in this particular field and motivate governments to increase % GDP for R&D for the benefit of patients suffering fromthese rare and disabling conditions.

    Matched MeSH terms: Multiple Sclerosis*
  19. Islam MA, Kundu S, Hassan R
    Curr Gene Ther, 2020;19(6):376-385.
    PMID: 32141417 DOI: 10.2174/1566523220666200306092556
    Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.
    Matched MeSH terms: Multiple Sclerosis/genetics*; Multiple Sclerosis/immunology*; Multiple Sclerosis/therapy*
  20. Ziganshin RH, Ivanova OM, Lomakin YA, Belogurov AA, Kovalchuk SI, Azarkin IV, et al.
    Mol Cell Proteomics, 2016 Jul;15(7):2366-78.
    PMID: 27143409 DOI: 10.1074/mcp.M115.056036
    Acute inflammatory demyelinating polyneuropathy (AIDP) - the main form of Guillain-Barre syndrome-is a rare and severe disorder of the peripheral nervous system with an unknown etiology. One of the hallmarks of the AIDP pathogenesis is a significantly elevated cerebrospinal fluid (CSF) protein level. In this paper CSF peptidome and proteome in AIDP were analyzed and compared with multiple sclerosis and control patients. A total protein concentration increase was shown to be because of even changes in all proteins rather than some specific response, supporting the hypothesis of protein leakage from blood through the blood-nerve barrier. The elevated CSF protein level in AIDP was complemented by activization of protein degradation and much higher peptidome diversity. Because of the studies of the acute motor axonal form, Guillain-Barre syndrome as a whole is thought to be associated with autoimmune response against neurospecific molecules. Thus, in AIDP, autoantibodies against cell adhesion proteins localized at Ranvier's nodes were suggested as possible targets in AIDP. Indeed, AIDP CSF peptidome analysis revealed cell adhesion proteins degradation, however no reliable dependence on the corresponding autoantibodies levels was found. Proteome analysis revealed overrepresentation of Gene Ontology groups related to responses to bacteria and virus infections, which were earlier suggested as possible AIDP triggers. Immunoglobulin blood serum analysis against most common neuronal viruses did not reveal any specific pathogen; however, AIDP patients were more immunopositive in average and often had polyinfections. Cytokine analysis of both AIDP CSF and blood did not show a systemic adaptive immune response or general inflammation, whereas innate immunity cytokines were up-regulated. To supplement the widely-accepted though still unproven autoimmunity-based AIDP mechanism we propose a hypothesis of the primary peripheral nervous system damaging initiated as an innate immunity-associated local inflammation following neurotropic viruses egress, whereas the autoantibody production might be an optional complementary secondary process.
    Matched MeSH terms: Multiple Sclerosis/immunology*
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