Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

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Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Autoimmune Diseases ◽

10.4061/2011/932351 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 14

Author(s):

Giulio Disanto ◽

Antonio J. Berlanga ◽

Adam E. Handel ◽

Andrea E. Para ◽

Amy M. Burrell ◽

...

Keyword(s):

Multiple Sclerosis ◽

Complex Disease ◽

Outcome Prediction ◽

Demyelinating Disease ◽

Clinical Course ◽

Personalised Medicine ◽

Specific Treatment ◽

Environmental Agents ◽

The Central Nervous System ◽

Different Populations

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research.

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Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

Multiple Sclerosis International ◽

10.1155/2013/614716 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

S. Viswanathan ◽

N. Rose ◽

A. Masita ◽

J. S. Dhaliwal ◽

S. D. Puvanarajah ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neuromyelitis Optica ◽

Demyelinating Disease ◽

Age At Onset ◽

Positive Family History ◽

Disease Onset ◽

Demyelinating Diseases ◽

Lesion Length ◽

Relapsing Remitting ◽

Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

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The induced dose of experimental autoimmune encephalomyelitis was not determinant and proportional to histopathological findings

European Journal of Public Health ◽

10.1093/eurpub/ckab120.080 ◽

2021 ◽

Vol 31 (Supplement_2) ◽

Author(s):

Maiara Carolina Perussolo ◽

Bassam Felipe Mogharbel ◽

Lucia de Noronha ◽

Katherine Athayde Teixeira de Carvalho

Keyword(s):

Spinal Cord ◽

Experimental Autoimmune Encephalomyelitis ◽

Demyelinating Disease ◽

Clinical Signs ◽

Signs And Symptoms ◽

Control Group ◽

Autoimmune Encephalomyelitis ◽

Histopathological Findings ◽

The Brain ◽

Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. It presents a diversity of neurologic signs and symptoms as well the incapacities. Since the need for advances in MS treatment, many studies are for new therapeutic technologies, mainly through using preclinical models as experimental autoimmune encephalomyelitis (EAE). This study aimed to observe and analyze the development in Lewis rats-induced model of EAE. Methods It was used 23 females of Rattus norvegicus, from 6 to 8 weeks, weighing around 170 g. Of 23 rats, 19 underwent EAE induction distributed in six groups to establish the evolution of clinical signs. B. pertussis toxin (PTX) doses were 200, 250, 300, 350–400 ng, and four animals as the control group. The animals had weight and scores analyzed daily, starting seven and ending 24 days after induction. Then, all animals were euthanized, and the brain and spinal cord were collected for histopathological analyses. Results The results showed that the dose of 250 ng of PTX induced de higher score and weight reduction. All groups who received the PTX demonstrated histopathological findings. Those characterized as leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brain. In the spinal cord, the loosening of the myelinated fibers was observed by increasing the axonal space in all tested doses of PTX. Conclusions EAE was not dose-dependent. Histopathological findings do not proportionally related to clinical signs, as in human patients with MS.

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Multiple sclerosis and other demyelinating diseases

10.1093/med/9780198569381.003.0871 ◽

2011 ◽

Author(s):

Alastair Compston

Keyword(s):

Multiple Sclerosis ◽

Demyelinating Disease ◽

Past History ◽

Central Pontine Myelinolysis ◽

Clinical Manifestations ◽

Nerve Impulse ◽

Demyelinating Diseases ◽

Clinical Neurology ◽

Disease Heterogeneity ◽

Axonal Dysfunction

The oligodendrocyte–myelin unit subserves saltatory conduction of the nerve impulse in the healthy central nervous system. At one time, many disease processes were thought exclusively to target the structure and function of myelin. Therefore, they were designated ‘demyelinating diseases’. But recent analyses, based mainly on pathological and imaging studies, (re)emphasize that axons are also directly involved in these disorders during both the acute and chronic phases. Another ambiguity is the extent to which these are inflammatory conditions. Here, distinctions should be made between inflammation, as a generic process, and autoimmunity in which rather a specific set of aetiological and mechanistic conditions pertain. And there are differences between disorders that are driven primarily by immune processes and those in which inflammation occurs in response to pre-existing tissue damage.With these provisos, the pathological processes of demyelination and associated axonal dysfunction often account for episodic neurological symptoms and signs referable to white matter tracts of the brain, optic nerves, or spinal cord when these occur in young people. This is the clinical context in which the possibility of ‘demyelinating disease’ is usually considered by physicians and, increasingly, the informed patient. Neurologists will, with appropriate cautions, also be prepared to diagnose demyelinating disease in older patients presenting with progressive symptoms implicating these same pathways even when there is no suggestive past history. Both in its typical and atypical forms multiple sclerosis remains by far the commonest demyelinating disease. But acute disseminated encephalomyelitis, the leucodystrophies, and central pontine myelinolysis also need to be considered in particular circumstances; and multiple sclerosis itself has a differential diagnosis in which the relapsing-remitting course is mimicked by conditions not associated with direct injury to the axon–glial unit. Since our understanding of the cause, pathogenesis and features of demyelinating disease remains incomplete, classification combines aspects of the aetiology, clinical features, pathology, and laboratory components. Whether the designation ‘multiple sclerosis’ encapsulates one or more conditions is now much debated. We anticipate that a major part of future studies in demyelinating disease will be further to resolve this question of disease heterogeneity leading to a new taxonomy based on mechanisms rather than clinical empiricism. But, for now, the variable ages of onset, unpredictable clinical course, protean clinical manifestations, and non-specific laboratory investigations continue to make demyelinating disease one of the more challenging diagnostic areas in clinical neurology.

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Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses

Multiple Sclerosis International ◽

10.1155/2018/8487471 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Maria P. Gontika ◽

Maria C. Anagnostouli

Keyword(s):

Multiple Sclerosis ◽

Early Onset ◽

Demyelinating Disease ◽

Age Of Onset ◽

Genetic Locus ◽

Human Leukocyte ◽

Myelin Oligodendrocyte Glycoprotein ◽

Demyelinating Diseases ◽

Disease Course ◽

Clinical Phenotypes

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patients with demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)—which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s—has also emerged as the primary genetic locus in early-onset MS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1⁎1501 and DRB1⁎0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS.

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Loss of HDAC11 ameliorates clinical symptoms in a multiple sclerosis mouse model

Life Science Alliance ◽

10.26508/lsa.201800039 ◽

2018 ◽

Vol 1 (5) ◽

pp. e201800039 ◽

Cited By ~ 10

Author(s):

Lei Sun ◽

Elphine Telles ◽

Molly Karl ◽

Fengdong Cheng ◽

Noreen Luetteke ◽

...

Keyword(s):

Multiple Sclerosis ◽

Mouse Model ◽

Experimental Autoimmune Encephalomyelitis ◽

Immune Cell ◽

Demyelinating Disease ◽

Demyelinating Diseases ◽

Clinical Severity ◽

Autoimmune Encephalomyelitis ◽

Immune Mediated ◽

Experimental Autoimmune

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system (CNS). There is no known cure for MS, and currently available drugs for managing this disease are only effective early on and have many adverse side effects. Results from recent studies suggest that histone deacetylase (HDAC) inhibitors may be useful for the treatment of autoimmune and inflammatory diseases such as MS. However, the underlying mechanisms by which HDACs influence immune-mediated diseases such as MS are unclear. More importantly, the question of which specific HDAC(s) are suitable drug targets for the potential treatment of MS remains unanswered. Here, we investigate the functional role of HDAC11 in experimental autoimmune encephalomyelitis, a mouse model for MS. Our results indicate that the loss of HDAC11 in KO mice significantly reduces clinical severity and demyelination of the spinal cord in the post-acute phase of experimental autoimmune encephalomyelitis. The absence of HDAC11 leads to reduced immune cell infiltration into the CNS and decreased monocytes and myeloid DCs in the chronic progressive phase of the disease. Mechanistically, HDAC11 controls the expression of the pro-inflammatory chemokine C–C motif ligand 2 (CCL2) gene by enabling the binding of PU.1 transcription factor to the CCL2 promoter. Our results reveal a novel pathophysiological function for HDAC11 in CNS demyelinating diseases, and warrant further investigations into the potential use of HDAC11-specific inhibitors for the treatment of chronic progressive MS.

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Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study

Brain ◽

10.1093/brain/awaa102 ◽

2020 ◽

Vol 143 (5) ◽

pp. 1431-1446 ◽

Cited By ~ 18

Author(s):

Yoshiki Takai ◽

Tatsuro Misu ◽

Kimihiko Kaneko ◽

Norio Chihara ◽

Koichi Narikawa ◽

...

Keyword(s):

Multiple Sclerosis ◽

Humoral Immunity ◽

Demyelinating Disease ◽

Myelin Oligodendrocyte Glycoprotein ◽

Demyelinating Diseases ◽

Perivascular Spaces ◽

Clinical Diagnoses ◽

Demyelinating Lesions ◽

Oligoclonal Igg ◽

Aqp4 Antibody

Abstract Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.

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Utilità della risonanza magnetica perfusionale nella diagnosi differenziale tra lesioni demielinizzanti e patologia multinfartuale

Rivista di Neuroradiologia ◽

10.1177/19714009970100s212 ◽

1997 ◽

Vol 10 (2_suppl) ◽

pp. 35-36

Author(s):

C. Micheli ◽

M. Gallucci ◽

O. Gagliardo ◽

G. Cardone ◽

G. B. Minio Paluello ◽

...

Keyword(s):

Multiple Sclerosis ◽

Arrival Time ◽

Demyelinating Disease ◽

Risonanza Magnetica ◽

Demyelinating Diseases ◽

Vascular Lesions ◽

Acquisition Time ◽

Conventional Mri ◽

Number Of Patients ◽

The Difference

20 pts affected by chronic cerebrovascular disease (10) and demyelinating disease (10) were studied by means of conventional MRI and T2*-w dynamic scans (6 slices acquired in 2“, 60 dynamic scans obtained for each slice, total acquisition time ?120”) with the aim of evaluating wether different patterns could be defined between infarctions and demyelinations. 5 subjects were excluded for different reasons. Signal intensity (SI) and transit time (BPAT = Bolus Peak Arrival Time) values were calculated from ROIs positioned on affected and contralateral non affected areas in each pt. In the group affected by demyelinating diseases, data from pathological ROIs were not significantly different from the contralateral, although the basal value of the lesions started from more elevated levels. On the contrary, pts affected by vascular lesions showed significantly different values of SI between pathological ROIs and apparently normal contralateral brain (χ2 test, p<0.001). In two cases, asymmetry of the BPAT due to extracranial carotid stenosis were recorded. In conclusion, our experience encourages the use of perfusional studies with the aim of characterizing pathological processes. The difference recorded between the two groups could suggest wider use of the technique when differential diagnosis between the two pathological entities is not simply obtainable by standard MRI (i.e.: Multiple Sclerosis vs. autoimmune vasculitides). The limited number of patients enrolled in this study makes our results to be considered non definitive, although encouraging.

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Syringomyelia in demyelinating disease of the central nervous system: Report of two cases

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1110657s ◽

2011 ◽

Vol 139 (9-10) ◽

pp. 657-660 ◽

Cited By ~ 1

Author(s):

Dejan Savic ◽

Slobodan Vojinovic ◽

Mirjana Spasic ◽

Zoran Peric ◽

Stevo Lukic

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Magnetic Resonance ◽

Demyelinating Disease ◽

Clinical Signs ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

The Central Nervous System

Introduction. Syringomyelia is a cavitary extension inside the spinal cord which can be either symptomatic or congenitally-idiopathic. Syringomyelia during the course of the disease in patients presenting with clinically definite multiple sclerosis was described earlier. Syringomyelia in patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis is unusual. Case Outline. We present two patients presenting with demy-elinating disease of the central nervous system with syringomyelia in the cervical and thoracic spinal cord. We did not find classical clinical signs of syringomyelia in our patients, but we disclosed syringomyelia incidentally during magnetic resonance exploration. Magnetic resonance exploration using the gadolinium contrast revealed the signs of active demyelinating lesions in the spinal cord in one patient but not in the other. Conclusion. Syringomyelia in demyelinating disease of the central nervous system opens the question whether it is a coincidental finding or a part of clinical features of the disease. Differentiation of the significance of syringomyelia finding in these patients plays a role in the choice of treatment concept in such patients.

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State-of-the-Art Review: Demyelinating Diseases in Indonesia

Multiple Sclerosis International ◽

10.1155/2021/1278503 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Hana Larassati ◽

Riwanti Estiasari ◽

Reyhan E. Yunus ◽

Paul M. Parizel

Keyword(s):

Multiple Sclerosis ◽

Demyelinating Disease ◽

State Of The Art ◽

Acute Disseminated Encephalomyelitis ◽

Demyelinating Diseases ◽

Diagnostic Process ◽

Imaging Features ◽

Indonesian Population ◽

The Central Nervous System ◽

Medical Advances

Demyelinating diseases are more common in Indonesia than previously believed. However, it is still a challenge for a country such as Indonesia to implement the scientific medical advances, especially in the diagnostic process of demyelinating diseases, to achieve the best possible outcome for these groups of patients, within the constraints of what is socially, technologically, economically, and logistically achievable. In this review, we address the 4 major classes of demyelinating disease: multiple sclerosis (MS), neuromyelitis optica (NMO), anti-MOG-associated encephalomyelitis (MOG-EM), and acute disseminated encephalomyelitis (ADEM), and discuss their prevalence, demographics, clinical diagnosis workup, and imaging features in the Indonesian population, as well as the challenges we face in their diagnosis and therapeutic approach. We hope that this overview will lead to a better awareness of the spectrum of demyelinating diseases of the central nervous system in Indonesia.

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