scholarly journals Signs of neuroinflammation outweigh neurodegeneration as predictors for early conversion to MS

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Nervana Mohamed El Fayomy ◽  
Hanan Helmy Mohamed ◽  
Manal Mohamed Kamal ◽  
Aya Hamid Alsayyad ◽  
Enas Hamid Alsayyad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Clinical Manifestations ◽  
Transcranial Sonography ◽  
Oligoclonal Bands ◽  
Lesion Load ◽  
Demyelinating Disorder ◽  
Significant Difference ◽  
A Prospective Study ◽  
Ultrasonographic Assessment

Abstract Background The pathophysiological mechanisms underlying multiple sclerosis include both inflammatory and degenerative processes. We aimed to study and compare markers of neuroinflammation and neurodegeneration in patients with first presentation of demyelinating disorder and to prospectively identify which of the studied markers serve as predictors for early conversion to multiple sclerosis. Thus, 42 patients with first clinical manifestations suggestive of demyelinating disease were included in a prospective study. Subjects underwent thorough history taking and clinical evaluation. Laboratory studies involved analysis of cerebrospinal fluid (CSF) and serum chitinase 3-like 1 levels. Brain imaging included MRI and ultrasonographic assessment. Results T1 black holes, elevated oligoclonal bands (OCB), high baseline T2 lesion load, and enhanced MRI lesions were significantly higher in patients with 1st attack multiple sclerosis. Significantly higher CSF-OCB and serum chitinase 3-like 1 protein was detected in patients with multiple sclerosis (MS) compared to clinically isolated syndrome, and higher levels in MS convertors than non-convertors. Cognitive dysfunction evaluated by MoCA test and brain atrophy assessed using transcranial sonography did not show significant difference among the studied groups. Logistic regression analysis showed that heavy T2 lesion load served as the only predictor of conversion to MS. Conclusion Early conversion to MS after first attack of demyelination is related to detection of signs of neuroinflammation rather than neurodegeneration.

Torticollis as an Initial Manifestation of a Seronegative Demyelinating Disorder in a Child: A Case Report

2021 ◽  
Author(s):  
Sandesh Kini ◽  
Yellanthoor Ramesh Bhat ◽  
Lakshmikanth Halegubbi Karegowda
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Case Report ◽  
Demyelinating Disease ◽  
Oligoclonal Bands ◽  
Initial Manifestation ◽  
Demyelinating Disorder ◽  
The Brain

AbstractTorticollis refers to a condition in which the head is persistently tilted to one side, sometimes associated with pain. Torticollis in a child can be congenital or acquired. Torticollis as an initial manifestation of an underlying demyelinating syndrome is quite rare in children. Here, we report a 7-year-old girl who presented with persistent torticollis. Neuroimaging of the brain revealed features of a demyelinating disease. Further studies did not show any evidence of multiple sclerosis. Cerebrospinal fluid was negative for antiaquaporin-4 antibodies, antimyelin oligodendrocyte glycoprotein antibodies, and oligoclonal bands. A seronegative demyelinating disorder was considered. She was treated with pulsed methylprednisolone therapy. She responded well to steroids with no progression of illness during follow-up. Torticollis was partially improved.

scholarly journals Cerebrospinal Fluid Analysis in Multiple Sclerosis Diagnosis: An Update

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 245 ◽  
Author(s):  
Bruna Lo Sasso ◽  
Luisa Agnello ◽  
Giulia Bivona ◽  
Chiara Bellia ◽  
Marcello Ciaccio
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Laboratory Diagnosis ◽  
Oligoclonal Bands ◽  
Csf Biomarkers ◽  
Laboratory Findings

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with brain neurodegeneration. MS patients present heterogeneous clinical manifestations in which both genetic and environmental factors are involved. The diagnosis is very complex due to the high heterogeneity of the pathophysiology of the disease. The diagnostic criteria have been modified several times over the years. Basically, they include clinical symptoms, presence of typical lesions detected by magnetic resonance imaging (MRI), and laboratory findings. The analysis of cerebrospinal fluid (CSF) allows an evaluation of inflammatory processes circumscribed to the CNS and reflects changes in the immunological pattern due to the progression of the pathology, being fundamental in the diagnosis and monitoring of MS. The detection of the oligoclonal bands (OCBs) in both CSF and serum is recognized as the “gold standard” for laboratory diagnosis of MS, though presents analytical limitations. Indeed, current protocols for OCBs assay are time-consuming and require an operator-dependent interpretation. In recent years, the quantification of free light chain (FLC) in CSF has emerged to assist clinicians in the diagnosis of MS. This article reviews the current knowledge on CSF biomarkers used in the diagnosis of MS, in particular on the validated assays and on the alternative biomarkers of intrathecal synthesis.

scholarly journals Clinical manifestations and imaging features of white matter demyelination in older patients

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096680
Author(s):  
Jian Li ◽  
Yi-Ming Zhao
Keyword(s):  
White Matter ◽  
Clinical Diagnosis ◽  
Older Patients ◽  
Demyelinating Disease ◽  
Clinical Manifestations ◽  
Imaging Features ◽  
Significant Difference ◽  
Clinical Diagnoses ◽  
Chief Complaints ◽  
Magnetic Resonance Imaging Mri

Objective To investigate the clinical manifestations and imaging features of older patients with white matter demyelination diagnosed by magnetic resonance imaging (MRI). Methods Ninety-six patients with leukoaraiosis diagnosed by MRI were divided by their clinical diagnoses into a demyelinating group (40 cases) and a non-demyelinating group (56 cases). The imaging and clinical features of the patients in the two groups were analyzed. Results Compared with the non-demyelinating group, there were significantly more women in the demyelinating group than men. There was no significant difference in age between the two groups. Of the 37 cases who had an imaging report of “white matter demyelination and multiple sclerosis,” 36 cases had a clinical diagnosis in accordance with white matter demyelination (97.3%). Of the 59 cases who had an imaging report of “white matter demyelination”, only four cases had a clinical diagnosis in accordance with demyelination (6.8%). Conclusion In older patients with headaches, vertigo, other head symptoms, and unilateral numbness as the chief complaints, a clinical diagnosis of demyelinating disease is very unlikely when the imaging report states white matter demyelination only.

Multiple sclerosis and other demyelinating diseases

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.

scholarly journals The Significance of HLA DRB1*1501 and Oligoclonal Bands in Multiple Sclerosis: Clinical Features and Disability

Medicina ◽  
2011 ◽  
Vol 47 (7) ◽  
pp. 368 ◽  
Author(s):  
Renata Balnytė ◽  
Daiva Rastenytė ◽  
Ingrida Ulozienė ◽  
Dalia Mickevičienė ◽  
Erika Skrodenienė ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Features ◽  
Clinical Symptoms ◽  
Oligoclonal Bands ◽  
Disability Score ◽  
Mcdonald Criteria ◽  
Disability Status ◽  
Igg Index ◽  
Degree Of Disability ◽  
A Prospective Study

The aim of the present study was to determine the value of immunogenetic risk factors and to estimate their relationship with the clinical features and disability status of patients with multiple sclerosis in a Lithuanian population. Materials and Methods. This was a prospective study of 80 patients with multiple sclerosis. The diagnosis of multiple sclerosis was based on the revised McDonald criteria. Oligoclonal bands (OCBs) of immunoglobulin G (IgG) were tested using isoelectric focusing and IgG specific immunofixation. HLA DRB1 alleles were genotyped using polymerase chain reaction. Results. Of all patients, 55% were positive for OCBs and 56% for HLA DRB1*1501. OCBpositive patients with multiple sclerosis had higher EDSS scores than their OCB-negative counterparts at onset of the disease (3.93±1.21 and 3.36±0.96 points, respectively; P=0.02) and during the last visit (4.31±2.06 and 3.09±1.98 points, respectively; P=0.009). The mean relapse rate was higher in the OCB-positive group compared with OCB-negative group (1.45±0.69 and 0.58±0.64, respectively; P=0.001). OCB-positive patients had higher IgG index compared with OCB-negative patients (P=0.0001). No relationship was found between HLA DRB1*1501 antigen status and the clinical features or EDSS score, and presence or absence of OCB in the present subset of patients with multiple sclerosis. Conclusions. The presence of oligoclonal bands in the cerebrospinal fluid of the patients with multiple sclerosis was associated with the greater number of exacerbations, higher degree of disability, and higher IgG index. There were no significant associations between the presence of HLA DRB1*1501 allele and the clinical symptoms, course of disease, or disability score.

Factors predicting incomplete recovery from relapses in multiple sclerosis: a prospective study

2008 ◽  
Vol 14 (4) ◽  
pp. 485-493 ◽  
Author(s):  
MA Leone ◽  
S. Bonissoni ◽  
L. Collimedaglia ◽  
F. Tesser ◽  
S. Calzoni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Mri ◽  
Total Duration ◽  
Oligoclonal Bands ◽  
Relapsing Remitting ◽  
Environmental Background ◽  
Maximum Improvement ◽  
A Prospective Study ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Speed Of Onset

Objective To prospectively evaluate predictors of incomplete recovery after the first attacks in a cohort of patients with clinically isolated syndrome or relapsing—remitting multiple sclerosis. Methods Seventy-two consecutive patients recruited from January 2001 to December 2003, evaluated every six months or at any relapse up to 31 July 2005. Relapse intervals were calculated from the date of onset, nadir, onset of improvement and maximum improvement. Predictive factors analysed were relapse-related (age at relapse onset, season and severity of the relapse, type of symptoms, speed of onset, plateau and total duration, number of affected Functional systems, preceding infections) and individual-related (gender, age at first attack, season of birth and first attack, characteristics of first brain MRI and cerebrospinal fluid oligoclonal bands, Link Index, IgG). Results We counted 209 attacks: 44 (21%) left mild sequelae, and 27 (13%) severe. The highest probability of sequelae was associated with sphincteric symptoms (9/20; 45%), followed by sensitive (38/113; 34%), motor (20/84; 24%), visual (13/61; 21%), cerebellar (4/24; 17%), brainstem (5/44; 11%) and others (0/6) ( P 0.005). Four variables were still relevant to predict sequelae after multivariate analysis: mild, moderate or severe relapses versus very mild (Odds ratio = 17.2, 95% confidence limits = 2.2—136.4), intermediate or long relapses versus short (3.2, 1.5—6.9), age ≥ 30 at relapse onset (2.9, 1.5—5.7) and bi-polysymptomatic versus monosymptomatic (2.2, 1.1—4.3). Conclusions Factors predicting incomplete recovery are more closely linked to the characteristics of the single relapse (extension and duration of tissue damage) than to the patient's genetic and environmental background. Multiple Sclerosis 2008; 14: 485—493. http://msj.sagepub.com

scholarly journals Free Light Chains and Intrathecal B Cells Activity in Multiple Sclerosis: A Prospective Study and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Gabriella Passerini ◽  
Gloria Dalla Costa ◽  
Francesca Sangalli ◽  
Lucia Moiola ◽  
Bruno Colombo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Inflammatory Diseases ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
The Other ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Free Light Chains ◽  
A Prospective Study

Background. The presence of CSF oligoclonal bands (OBs) is an independent prognostic factor for multiple sclerosis (MS), but the difficulties in the standardization of the test and the interlaboratory variation in reporting have contributed to its limited use in the diagnosis of the disease. Standard nephelometric assays to measure free light chains (FLC) levels have been recently developed and the test may improve the detection of intrathecal B cells activity.Methods. The presence of OBs, kappa and lambda FLC levels, and standard indices of intrathecal inflammation were assessed in 100 consecutive patients, including patients with MS, clinically isolated syndromes (CIS), other inflammatory diseases of the CNS, and other noninflammatory diseases.Results. Both KFLC and LFLC correlated strongly with the presence of OCBs and with all common tests for intrathecal inflammation (p<0.001for all comparisons). KFLC and LFLC were significantly different in patients with MS and CIS compared to the other groups (p<0.001andp<0.001, resp.) and had a better diagnostic accuracy than all the other tests (area under the curve 82.3 % for KFLC index and 79.3 % for LFLC index).Conclusion. Nephelometric assays for KFLC in CSF reliably detect intrathecal immunoglobulin synthesis and discriminate MS patients.

scholarly journals Bilateral internuclear ophthalmoplegia in multiple sclerosis of very late onset

2021 ◽  
Author(s):  
Guilherme Drumond Jardini Anastacio ◽  
Stella de Angelis Trivellato ◽  
Hendrick Henrique Fernandes Gramasco ◽  
Ana Claudia Pires Carvalho ◽  
Omar Gurrola Arambula ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual Acuity ◽  
Demyelinating Disease ◽  
Hip Prosthesis ◽  
Age Of Onset ◽  
Late Onset ◽  
Oligoclonal Bands ◽  
Internuclear Ophthalmoplegia ◽  
Lower Limb Pain ◽  
The Right

Context: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. The average age of onset is in the range of 28 to 31 years, but it can occur from the first year of life or after the seventh decade. If diagnosed over 60 years of age, it is called very late onset, with low prevalence. Bilateral internuclear ophthalmoplegia is a rare syndrome characterized by bilateral restriction of the adduction of the eyes in the conjugated horizontal gaze, which is generally secondary to demyelinating and vascular diseases. Case report: A 64-year-old man, brown, with a history of alcoholism, gout, hypothyroidism, arterial hypertension and generalized osteoarthritis with a right hip prosthesis with difficulty walking, presented a five-day subacute bilateral visual turbidity and binocular horizontal diplopia. On physical examination, he presented bilateral internuclear ophthalmoplegia, with a reduction in bilateral visual acuity worse on the right, in addition to lower limb pain pseudoparesis, with bilateral Babinski sign. Investigation with visual evoked potential demonstrated bilateral demyelinating optic neuropathy on the right, cerebrospinal fluid with more than two oligoclonal bands present, neuroaxis magnetic resonance imaging showing a change in the signal of the right optic nerve and multiple demyelinating lesions, fulfilling the criteria for dissemination in space and time. Therapy with Methylprednisolone 1g / day for 5 days was performed, with improvement of the condition, maintaining only visual sequelae with decreased visual acuity, and disease-modifying therapy was also started with stabilization of the condition. Conclusions: Despite being more rare, very late-onset MS should be considered as a diagnosis, even with singular presentations as in the case reported.

111 Epileptic seizures in multiple sclerosis

2018 ◽  
Vol 89 (6) ◽  
pp. A44.1-A44
Author(s):  
Stephen Walsh ◽  
Joel Corbett ◽  
K Meng Tan ◽  
Simon Broadley
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Age Of Onset ◽  
Case Reports ◽  
Case Series ◽  
Clinical Information ◽  
Epileptic Seizures ◽  
Disease Course ◽  
Number Of Patients ◽  
Significant Difference

IntroductionEpileptic seizures have been described in association with multiple sclerosis (MS) in both anecdotal case reports and case series. The recent identification of specific antibodies to myelin oligodendrocyte glycoprotein (MOG) protein in a small number of patients with demyelinating disease which may resemble neuromyelitis optica or acute disseminated encephalopathy, which may involve seizures, raises the possibility that anti-MOG antibody related demyelination may account for the association of epilepsy with MS.MethodsWe have undertaken a retrospective review of cases of MS diagnosed at the Gold Coast MS clinic over a 10 year period. All cases were systematically asked if they had ever had an epileptic seizure either via a patient completed questionnaire or at a clinic visit. Demographic and clinical information were also recorded. These data have been analysed using descriptive statistics and appropriate tests for significant differences between those with epilepsy and those without.Results428 cases with complete data were identified. Those with a history of epilepsy were slightly younger (median (range); 44.5 (27–64) years vs 4715–88 years), but this difference was not statistically significantly different. The gender ratio was the same for both groups (9/12 (75%) for those with epilepsy and 326/416 (78%)). There was no significant difference in age of onset, disease course, relapse frequency or level of disability. Although numbers are small, seizure appear to occur most frequently earlier in the disease course and are rarely an ongoing issue.ConclusionThese data support earlier work indicating that epilepsy occurs in people with MS who are younger. This fits with the notion that seizures arise in the context of the inflammatory stage of multiple sclerosis rather than the degenerative phase. Further work needs to be undertaken to assess any association with anti-MOG antibodies and epileptic seizures in demyelinating disease.

scholarly journals Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin

2004 ◽  
Vol 10 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Mónica Santos ◽  
Maria do Carmo Costa ◽  
Maria Edite Rio ◽  
Maria José Sá ◽  
Marta Monteiro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prognostic Markers ◽  
Demyelinating Disease ◽  
Age At Onset ◽  
Progression Rate ◽  
Clinical Context ◽  
Portuguese Population ◽  
Significant Difference ◽  
S Alleles ◽  
Rate Of Progression

Multiple sclerosis (MS) is a demyelinating disease that affects about one in 500 young Europeans. In order to test the previously proposed influence of the A PO E and SC A 2 loci on susceptibility to MS, we studied these loci in 243 Portuguese patients and 192 healthy controls and both parents of 92 patients. We did not detect any significant difference when A PO E and SC A 2 allele frequencies of cases and controls were compared, or when we compared cases with different forms of the disease. Disequilibrium of transmission was tested for both loci in the 92 trios, and we did not observe segregation distortion. To test the influence of the A PO E o4 and SC A 2 22 C AGs alleles on severity of disease, we compared age at onset and progression rate between groups with and without those alleles. We did not observe an association of the o4 or the 22 C AG s alleles with rate of progression in our total patient population; allele o4 was associated with increased rate of progression of MS in a subset of patients with less than 10 years of the disease. However, globally in the Portuguese population, the A PO E and SC A2 genes do not seem to be useful in the clinical context as prognostic markers of this disorder.

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