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Multiple sclerosis. The neuropathology of a case with a plea

Arumugasamy N

Med J Malaya, 1969 Sep;24(1):45-8.
PMID: 4243843
Matched MeSH terms: Multiple Sclerosis/pathology*
Multiple sclerosis in Malaysia

Tan CT

Arch. Neurol., 1988 Jun;45(6):624-7.
PMID: 3369969

Thirty consecutive patients from peninsular Malaysia with clinically definite multiple sclerosis were studied; 80% were ethnic Chinese, with a female-male ratio of 5:1. The average age at onset was 29.7 years, with one relapse average every 1.9 years. Optic-spinal recurrence was the most common clinical pattern of the disease, accounting for 63.3% (19/30) of the cases. All the patients had spinal cord involvement sometime during the course of the illness. The mortality was high at 36.7% (11/30), with an average duration of symptoms of 7.6 years. There was characteristic severe residual visual and motor disability. At the time of the last examination, 12 patients had bilateral optic atrophy with blindness or severe visual acuity impairment. Sixteen patients were bedridden or confined to a wheelchair. The severe motor disability reflected the severe spinal cord involvement. It was the main factor that accounted for the high mortality. The cerebral, cerebellar, and brain-stem involvements were, however, generally transient. None of the patients' had a family history of similar illness despite the average sibling size of six. There was no example of Devic's disease. The clinical pattern was closest to those patients who presented from Taiwan.

Matched MeSH terms: Multiple Sclerosis/complications*; Multiple Sclerosis/epidemiology
Fulltext Clinically definite multiple sclerosis in a young Malay female. A case report

Muthusamy E, Tan CT

Med J Malaysia, 1988 Jun;43(2):170-2.
PMID: 3237134
Matched MeSH terms: Multiple Sclerosis/diagnosis*; Multiple Sclerosis/physiopathology
Prognosis of patients who present with an episode of myelopathy of unknown origin in Malaysia: a retrospective study of 52 patients

Tan CT

Aust N Z J Med, 1989 Aug;19(4):297-302.
PMID: 2783084

Fifty-four per cent of 52 patients presenting to the University of Malaya Medical Centre with a myelopathy for which appropriate investigations uncovered no definite etiology, subsequently developed clinically definite or probable multiple sclerosis. In the subgroup of patients with a presentation indicative of acute/subacute transverse myelopathy, 14 or 52% also went on to develop clinically definite or probable multiple sclerosis, a far higher proportion than previously recorded in the literature. This finding is probably a further manifestation of racial difference in the behaviour of multiple sclerosis. For the group as a whole, the only factor which appeared to be associated with an increased risk of developing multiple sclerosis was female sex; 67% of 33 female patients went on to develop multiple sclerosis after a mean follow-up period of 5.5 years. Other factors such as age of onset, racial composition, level of spinal cord involvement, presence of fever and CSF finding were found not to be important.

Matched MeSH terms: Multiple Sclerosis/complications; Multiple Sclerosis/diagnosis*; Multiple Sclerosis/ethnology
CT scan changes in multiple sclerosis among Malaysian patients

Tan CT, Abdullah D, Zakariya AH

Neuroradiology, 1991;33(6):494-8.
PMID: 1780049

A study of 12 patients with clinically definite multiple sclerosis (CDMS) using high dose infusion CT showed overall abnormality of 75% with an average of 2.5 lesions per patient. 75% of the patients showed abnormality of the cerebrum, mostly asymptomatic. The main changes were ventricular dilatation and asymmetry, isolated or generalized cerebral atrophy, areas of low attenuation mainly in the deeper parts of the cerebrum and the peri-ventricular area. 25% of the patients showed changes in the brainstem and none was seen in the cerebellum. The abnormality was more florid in patients with clinically disseminated forms of the disease. The study demonstrated that asymptomatic cerebral involvement is common among Asian patients with MS and CT is a useful tool in the overall assessment and diagnosis of Asian MS patients.

Matched MeSH terms: Multiple Sclerosis/ethnology; Multiple Sclerosis/pathology
Fulltext Evoked response study among Malaysian multiple sclerosis patients

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*
Fulltext The hot bath test among Malaysian multiple sclerosis patients

Tan CT

Med J Malaysia, 1994 Mar;49(1):68-73.
PMID: 8057994

This is a study of 13 Malaysian patients with clinically definite Multiple sclerosis (MS) subjected to a hot bath test with VEPs, BAEPs, median nerve SSEPs before and after heating. Five patients (38%) developed neurological changes with the rise in body temperature. There was an average of 0.46 new sign per patient. Four patients had motor disturbances attributed mainly to aggravation of spinal cord dysfunction. Two patients had additional visual deterioration, one patient has associated VEP change. This study shows that though Uhthoff's phenomenon has not been noted in the reports of Asian MS patients, when subjected to rigorous testing, Asian MS patients also show sensitivity to body temperature change. However, the percentage of positivity of the hot bath test is much lower than that reported for Caucasians. Thus this study shows further differences between Asian and Caucasian MS patients.

Matched MeSH terms: Multiple Sclerosis/diagnosis*; Multiple Sclerosis/genetics; Multiple Sclerosis/epidemiology; Multiple Sclerosis/physiopathology*
Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West

Chong HT, Ramli N, Lee KH, Kim BJ, Ursekar M, Dayananda K, et al.

Can J Neurol Sci, 2006 Feb;33(1):95-100.
PMID: 16583730

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.

Matched MeSH terms: Multiple Sclerosis/pathology*
Fulltext A review of multiple sclerosis with Asian perspective

Chong HT, Tan CT

Med J Malaysia, 2008 Dec;63(5):356-61.
PMID: 19803290 MyJurnal

Multiple sclerosis, although a rare disease in Asia, often presents significant diagnostic challenges to clinicians. There has been rapid advancement in the understanding of the underlying genetic influence, pathophysiology, investigation and treatment recently. This paper reviewed the latest development of various aspects of the disease and examined the differences between the manifestations of Asian and Western patients. The implications of these differences to investigation and treatment were also touched upon.

Matched MeSH terms: Multiple Sclerosis/diagnosis; Multiple Sclerosis/ethnology*; Multiple Sclerosis/therapy
The past, present and future of imaging in multiple sclerosis

Ramli N, Rahmat K, Azmi K, Chong HT

J Clin Neurosci, 2010 Apr;17(4):422-7.
PMID: 20167498 DOI: 10.1016/j.jocn.2009.09.014

Despite technological advances in imaging, multiple sclerosis (MS) remains a clinical diagnosis that is supported, but not replaced, by laboratory or imaging findings. However, imaging is essential in the current diagnostic criteria of MS, for prediction of the likelihood of MS for patients with clinically isolated syndromes, correlation with lesion pathology and assessment of treatment outcome. This article gives an overview of imaging in MS with particular emphasis on the role of MRI in various diagnostic imaging criteria. Novel imaging for MS using 3 Tesla field strengths, magnetization transfer imaging, diffusion tensor imaging, magnetic resonance spectroscopy and cell-specific contrast will be reviewed.

Matched MeSH terms: Multiple Sclerosis/pathology*
Asian adaptation and validation of an English version of the multiple sclerosis international quality of life questionnaire (MusiQoL)

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*
Glutamate receptors and transporters as comparative cues to the glutamatergic circuits of the avian and mammalian brain

Islam, M.R., Muzaimi, M., Abdullah, J.M.

Orient Neuron Nexus, 2011;2(1):2-9.
MyJurnal

Glutamate is the principal excitatory neurotransmitter in the central nervous system, and plays important roles in both physiological and pathological neuronal processes. Current understanding of the exact mechanisms involved in glutamate-induced neuronal excitotoxicity, in which excessive glutamate causes neuronal dysfunction and degeneration, whether acute or chronic, remain elusive. Conditions, due to acute insults such as ischaemia and traumatic brain injury, and chronic neurodegenerative disorders such as multiple sclerosis and motor neuron disease, suffer from the lack of translational neuroprotection in clinical setting to tackle glutamate excitotoxicity despite steady growth of animal studies that revealed complex cell death pathway interactions. In addition, glutamates are also released by non-neuronal cells including astrocytes and oligodendroglia. Thus, attempts to elucidate this complexity are closely related to our understanding of the glutamatergic circuitry in the brain. Neuronal cells develop a glutamatergic system at glutamatergic synapses that utilise glutamate as an intercellular signaling molecule to characterise the output, input, and termination of this signaling. As to signal input, various kinds of glutamate receptors have been identified and characterized. Na+-dependent glutamate transporters at the plasma membrane are responsible for the signal termination through sequestration of glutamate from the synaptic cleft. The signal output systems comprise vesicular storage and subsequent exocytosis of glutamate by using vesicular glutamate transporters. Similar to the mammalian brain, the regional differences of glutamatergic neurons and glutamate receptor neurons suggest many glutamatergic projections in the avian brain, as supported by recent evidence of glutamate-related genes distribution. Glutamatergic target areas are expected to show high activity of glutamate transporters that remove released glutamate from the synaptic clefts. This review summarises and compares glutamatergic circuits in the avian and mammalian brain, particularly in the olfactory pathway, the paffial organization of glutamatergic neurons and connection with the striatum, hippocampal-septal pathway, visual and auditory pathways, and granule cell-Purkinje cell pathway in the cerebellum. Comparative appreciation of these glutamatergic circuits, particularly with the localisation and/or expression of specific subtypes of glutamate transporters, would provide the morphological basis for physiological and pharmacological designs that supplement existing animal studies of the current proposed mechanisms that underlie glutamate-induced neuronal excitotoxicity.

Matched MeSH terms: Multiple Sclerosis
Fulltext Encephalitis followed by optic neuritis: a case report and review of literature

Hasan S, B Basri H, P Hin L, Stanslas J

Pak J Med Sci, 2013 May;29(3):859-62.
PMID: 24353644

Encephalitis has been included in the causes of optic neuritis, but post encephalitic optic neuritis has been rarely reported. Majority of the cases of optic neuritis are either idiopathic or associated with multiple sclerosis, especially in western countries. This is very important in the Asian population where the incidence and prevalence of multiple sclerosis is not as high as in the Western countries. Although post infectious optic neuritis is more common in children, it can also be found in adults and is usually seen one to three weeks after a symptomatic infective prodrome. Here, we present a case of a 48 year-old-male who developed optic neuritis following viral encephalitis. His first presentation was with severe headache of two weeks duration. Viral encephalitis was diagnosed and treated. The patient presented again three weeks later with right eye pain and other features typical of optic neuritis. Corticosteroid therapy facilitated prompt recovery. Optic neuritis is an uncommon manifestation of encephalitis. It is important that both doctors and patients remain aware of post infectious cause of optic neuritis, which would enable a timely diagnosis and treatment of this reversible cause of vision loss.

Matched MeSH terms: Multiple Sclerosis
A previously misdiagnosed cohort of aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder with disease duration of >10 years in multi-ethnic Penang, Malaysia: Clinical features and disease course

Hor JY, Lim TT, Chow HB, Tan K, Cheah CF, Ching YM, et al.

Mult Scler Relat Disord, 2016 Jan;5:89-90.
PMID: 26856950 DOI: 10.1016/j.msard.2015.11.008
Matched MeSH terms: Multiple Sclerosis/diagnosis*; Multiple Sclerosis/immunology*
Autoantibodies to tetraspanins (CD9, CD81 and CD82) in demyelinating diseases

Miyaji K, Paul F, Shahrizaila N, Umapathi T, Yuki N

J Neuroimmunol, 2016 Feb 15;291:78-81.
PMID: 26857499 DOI: 10.1016/j.jneuroim.2015.12.012

Tetraspanin family proteins, CD9, CD81 and CD82 are expressed in the oligodendrocytes and Schwann cells. We investigated autoantibodies to tetraspanin proteins in patients with demyelinating diseases. Sera were collected from 119 multiple sclerosis patients, 19 neuromyelitis optica, 42 acute inflammatory demyelinating polyneuropathy, 23 chronic inflammatory demyelinating polyneuropathy and 13 acute motor axonal neuropathy as well as 55 healthy controls. Few multiple sclerosis and acute inflammatory demyelinating polyneuropathy patients had autoantibodies that were weakly reactive to CD9 or CD81 but the significance is unclear. It is unlikely that these autoantibodies are pathogenic or serve as potential biomarkers in demyelinating diseases.

Matched MeSH terms: Multiple Sclerosis/blood*
Fulltext The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and Immunological Profiling of Physiological Fluids

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*
Natalizumab-Related Progressive Multifocal Leukoencephalopathy-Immune Reconstitution Inflammatory Syndrome: A Case Report Highlighting Clinical and MRI Features

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
Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases

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
Fulltext Extraction, Analytical and Advanced Methods for Detection of Allura Red AC (E129) in Food and Beverages Products

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
Fulltext Interference Effect of Prior Explicit Information on Motor Sequence Learning in Relapsing-Remitting Multiple Sclerosis Patients

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

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