Clinical and diagnostic aspects of multiple sclerosis and acute monophasic encephalomyelitis in pediatric patients: a single centre prospective study

Objective The purpose of the study was to compare and contrast the initial presenting demographic, clinical, neuroimaging, and laboratory features in a cohort of children affected from multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Methods A 12-year prospective study was conducted in 68 pediatric patients (age ≤ 17 years) who presented with a first episode of central nervous system inflammation suggestive of a demyelinating multifocal pathology. All patients had undergone magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination. The mean follow-up period, as at ending on December 31, 2007, was 6.8 ± 2.7 years (range 3.2–12.6 years). Results At clinical onset, children who developed MS during the follow-up (48 patients; 34 females, 14 males; mean age at onset: 14.4 ± 2.5) significantly differed from children affected by ADEM (20 patients; 8 females, 12 males; mean age at onset: 8.1 ± 3.8 ) for the following parameters: prevalence of females affected (female/male ratio: 2.8 versus 0.6, P = 0.03); mean age at onset ( P < 0.001); monosymptomatic onset (73% vs 30%, P = 0.002); encephalopathy-like onset (0% vs 50%, P < 0.001); presence of oligoclonal IgG bands (IgGOB) in CSF (83% vs 10%, P < 0.001); and periventricular (79% vs 20%, P < 0.001), brain stem (12.5% vs 60%, P = 0.000), and basal ganglia (10% vs 50%, P < 0.001) lesions at MRI. Conclusions Our findings depict a pattern of demographic, clinical, neuroimaging, and laboratory findings that can help to distinguish, at clinical onset, children suffering from ADEM from those who will develop MS. Childhood-onset MS seems not to differ from adult-onset MS from both clinical and paraclinical features.

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Multifocal Balo's Concentric Sclerosis in Children: Report of a Case and Review of Literature

Journal of Neurosciences in Rural Practice ◽

10.4103/jnrp.jnrp_504_16 ◽

2017 ◽

Vol 08 (S 01) ◽

pp. S136-S138

Author(s):

Sanjeev Kumar Bhoi ◽

Suprava Naik ◽

Jayantee Kalita ◽

U. K. Misra

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Acute Disseminated Encephalomyelitis ◽

Review Of Literature ◽

Resonance Imaging ◽

Concentric Pattern ◽

Baló’S Concentric Sclerosis ◽

Magnetic Resonance Imaging Mri ◽

Post Infectious

ABSTRACTBalo's concentric sclerosis (BCS) is a rare demyelinating lesion considered to be a variant of multiple sclerosis (MS). On magnetic resonance imaging (MRI) Balo's concentric sclerosis shows the typical concentric pattern. We report a case of 10 year old child with BCS who presented as post infectious acute disseminated encephalomyelitis (ADEM). He is asymptomatic and had no relapse after 6 years of follow-up.

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Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Spanish cohort of patients with clinically isolated syndromes

Multiple Sclerosis Journal ◽

10.1177/1352458511417828 ◽

2011 ◽

Vol 18 (1) ◽

pp. 39-44 ◽

Cited By ~ 27

Author(s):

M Gómez-Moreno ◽

M Díaz-Sánchez ◽

A Ramos-González

Keyword(s):

Multiple Sclerosis ◽

Mri Scan ◽

Clinically Isolated Syndromes ◽

Mcdonald Criteria ◽

International Panel ◽

Clinical Onset ◽

Magnetic Resonance Imaging Mri ◽

Sensitivity Specificity ◽

New Criteria

Background: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate the accuracy of these new criteria for lesions dissemination in space (DIS) and time (DIT), from a single MRI scan, to predict conversion from CIS to clinically definite MS. Methods: We studied 67 CIS patients with baseline MRI performed within the first 3 months after onset. The follow-up was of at least 24 months. The sensitivity, specificity and accuracy of Barkhof–Tintoré criteria and the new proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0. Results: The mean age for clinical onset was 30 years and 64% of patients were female. The overall conversion rate was 74%. In our cohort, Barkhof–Tintoré criteria showed a sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan in 54 patients with baseline scans that included gadolinium-enhanced images. The sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy of 59.26%. Conclusion: New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis.

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Partial acute transverse myelitis is a predictor of multiple sclerosis in children

Multiple Sclerosis Journal ◽

10.1177/1352458514526943 ◽

2014 ◽

Vol 20 (11) ◽

pp. 1485-1493 ◽

Cited By ~ 3

Author(s):

P Meyer ◽

N Leboucq ◽

N Molinari ◽

A Roubertie ◽

M Carneiro ◽

...

Keyword(s):

Multiple Sclerosis ◽

Prognostic Factors ◽

Severe Disease ◽

Brain Mri ◽

Age At Onset ◽

Transverse Myelitis ◽

First Episode ◽

Acute Transverse Myelitis ◽

Subsequent Risk

Background: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. Objectives: To determine the clinical course and prognostic factors after a first episode of ATM in children. Methods: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. Results: Median age at onset was 11 years (range 3–15 years). Follow-up data were available for a median of 4 years (range 0.5–16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3–11), with a 60% probability of having a relapse at five years ( p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). Conclusion: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.

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Pediatric onset multiple sclerosis: McDonald criteria 2010 and the contribution of spinal cord MRI

Multiple Sclerosis Journal ◽

10.1177/1352458513493033 ◽

2013 ◽

Vol 19 (10) ◽

pp. 1330-1335 ◽

Cited By ~ 23

Author(s):

Hannah-Maria Hummel ◽

Wolfgang Brück ◽

Steffi Dreha-Kulaczewski ◽

Jutta Gärtner ◽

Jens Wuerfel

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Age At Onset ◽

Regional Distribution ◽

Pediatric Multiple Sclerosis ◽

Mcdonald Criteria ◽

Spinal Mri ◽

Magnetic Resonance Imaging Mri ◽

Pediatric Onset

Background: Diagnostic magnetic resonance imaging (MRI) criteria have not been sufficiently validated in pediatric multiple sclerosis (MS) despite differences in epidemiologic data and clinical disease courses between pediatric and adult MS. Objective: The objective of this paper is to evaluate the diagnostic applicability and validity of the revised McDonald diagnostic criteria 2010 in a large cohort of pediatric-onset MS patients (POMS) and compare them to previously recommended MRI-based classifications. Furthermore, we aimed to investigate the contribution of spinal cord lesions to the revised McDonald criteria 2010. Methods: A cohort of 85 patients with definite MS, age at onset 2.8–18 years, was analyzed in a retrospective multicenter study. Number and regional distribution of T2w and contrast-enhancing T1w lesions at initial and follow-up MRIs were main outcome measures. Results: In 62% of POMS the initial MRI within four weeks after symptom onset was sufficient to diagnose MS according to the revised McDonald criteria 2010. In a subcohort of patients with spinal MRI at first presentation, 10% reached the dissemination in space (DIS) and dissemination in time (DIT) criteria only by the inclusion of contrast-enhancing spinal lesions. Conclusions: The revised McDonald criteria 2010 facilitate the diagnosis of POMS already at first presentation. The addition of a spinal cord MRI was helpful only in selected cases.

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Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome

Neurology ◽

10.1212/wnl.0000000000004312 ◽

2017 ◽

Vol 89 (9) ◽

pp. 900-908 ◽

Cited By ~ 133

Author(s):

Eva-Maria Hennes ◽

Matthias Baumann ◽

Kathrin Schanda ◽

Banu Anlar ◽

Barbara Bajer-Kornek ◽

...

Keyword(s):

Age At Onset ◽

Disease Onset ◽

Acute Disseminated Encephalomyelitis ◽

Oligoclonal Bands ◽

First Episode ◽

Cell Counts ◽

Csf Cells ◽

Younger Age ◽

Mog Antibodies

Objective:To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS).Methods:Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study.Results:Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG-ab cutoff titer ≥1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%.Conclusions:Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course.

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Predictive role of evoked potential examinations in patients with clinically isolated optic neuritis in light of the revised McDonald criteria

Multiple Sclerosis Journal ◽

10.1177/1352458507085061 ◽

2008 ◽

Vol 14 (4) ◽

pp. 472-478 ◽

Cited By ~ 10

Author(s):

Magdolna Simó ◽

Péter Barsi ◽

Zsuzsanna Arányi

Keyword(s):

Multiple Sclerosis ◽

Optic Neuritis ◽

Motor Evoked Potentials ◽

First Episode ◽

Clinical Criteria ◽

Mcdonald Criteria ◽

Mri Scans ◽

Magnetic Resonance Imaging Mri

To analyse the sensitivity and role of somatosensory and motor evoked potentials (EP) in patients with a first episode of clinically isolated optic neuritis (ON) in predicting the development and course of multiple sclerosis (MS), 27 patients with ON underwent EP and magnetic resonance imaging (MRI) examinations at presentation. Follow-up MRI scans were also performed (mean: 20, range: 4—48 months). It was found that 2/27 patients did not fulfill the MRI (McDonald) and clinical criteria of MS upon follow-up and also had normal EP results. Abnormal EP results were found in 6/27 patients and all of them had follow-up MRI results fulfilling the revised McDonald criteria of MS; 4/6 patients in this group were also diagnosed as clinically definitive MS. The majority, 19/27 patients had normal EP results, but went on to develop MS based on follow-up MRI results and McDonald criteria. Of these patients, however, only 3/19 converted to clinically definitive MS as well. The baseline MRI was abnormal in similar proportions (4/6 and 12/19) in these last two groups of patients. Thus, abnormal EP examinations at the first episode of ON can be considered as a predictive factor only for the earlier clinical conversion to MS — in this respect, however, being more sensitive than the initial MRI — and as such they may contribute to the delineation of the patient group who may benefit from early immunomodulatory treatment. They do not however have a predictive value for the development of MS itself as diagnosed by the McDonald criteria. Multiple Sclerosis 2008; 14: 472—478. http://msj.sagepub.com

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Abstract 3729: Delayed Hematoma Expansion Occurs After ICH: Observations from the Safety of Pioglitazone for Hematoma Resolution in INtraCerebral Hemorrhage (SHRINC) trial

Stroke ◽

10.1161/str.43.suppl_1.a3729 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Navdeep S Sangha ◽

Farhaan Vahidy ◽

Mallikarjunarao Kasam ◽

Mohammed Rahbar ◽

Bursaw Andrew ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Prospective Study ◽

Univariate Analysis ◽

Primary Objective ◽

Hematoma Expansion ◽

Hematoma Growth ◽

Secondary Objective ◽

Magnetic Resonance Imaging Mri ◽

Associated Risk Factors

Background and Purpose Early hematoma expansion (EHE) has been described in the first 48 hours. SHRINC is a phase 2 prospective safety trial whose primary objective is to assess the safety of pioglitazone (PIO) when administered to patients with spontaneous intracerebral hemorrhage (SICH) compared to standard care. A secondary objective is to characterize the changes in hematoma resolution and expansion over time. This prospective study addresses the natural history, clinical impact, and associated risk factors of late hematoma expansion (LEX) by serial magnetic resonance imaging (MRI) after SICH. Methods SHRINC aims to enroll 78 subjects between the ages of 18-80 with a SICH of ≥ 5 ml. This analysis includes the first 42 patients enrolled. Four subjects were excluded because they did not have an MRI after day 2. A baseline CTH was performed followed by an MRI within 24 hours of symptom onset. Hematoma volume (Hv) was measured on FLAIR sequences using a previously published semi-automated range of interest method. LEX was defined as an increase in Hv > 0.5 ml after the 48 hour MRI. Factors associated with LEX were evaluated with logistic regression. Longitudinal analyses were used for measurements taken over the follow up period. Results: Ten (26.3%) of 38 subjects displayed LEX. Eight subjects had LEX between day 2 to 14, and 4 between days 14 to 28. The median initial Hv was 16.1cc in LEX patients and 24.1cc in those without expansion (NEX) (p=0.23). Lower platelet counts (p=0.04) and BUN levels (p=0.03) were associated with LEX in univariate analysis. Multivariate analysis suggested that those with higher BUN levels were less likely to have LEX (OR=0.81; 95%CI 0.65-0.99). Blood pressure and EHE (13.2%) were not associated with LEX. There was no difference in neurological worsening (NIHSS increase ≥ 4), 6 month mRS or death between LEX and NEX. Conclusion: This is the first prospective study to address LEX with serial MRIs. LEX occurs between day 2 to 14 and day 14 to 28. Elevated BUN levels may decrease the likelihood of LEX. A limitation of our study is that the effect of PIO on LEX could not be evaluated because SHRINC is a blinded trial. Further studies will assess the pathophysiology of LEX and its potential implications in clinical trials evaluating hematoma growth and resolution.

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Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US

Neurology ◽

10.1212/wnl.0000000000006471 ◽

2018 ◽

Vol 91 (19) ◽

pp. e1778-e1787 ◽

Cited By ~ 17

Author(s):

Kristen M. Krysko ◽

Jennifer Graves ◽

Mary Rensel ◽

Bianca Weinstock-Guttman ◽

Gregory Aaen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Side Effect ◽

Pediatric Patients ◽

Dimethyl Fumarate ◽

Short Term ◽

Pediatric Multiple Sclerosis ◽

Disease Modifying Therapies ◽

The Us ◽

Disease Modifying

ObjectiveTo characterize the use and safety of newer disease-modifying therapies (DMTs) in children with multiple sclerosis (MS) and clinically isolated syndrome (CIS) treated under 18 years of age.MethodsThis is a cohort study including children with MS or CIS followed at 12 outpatient practices participating in the US Network of Pediatric MS Centers. DMT use, including duration, dose, and side effects, was analyzed. Newer DMTs were defined as agents receiving Food and Drug Administration approval or with increased use in adult MS after 2005.ResultsAs of July 2017, 1,019 pediatric patients with MS (n = 748) or CIS (n = 271) were enrolled (65% female, mean onset 13.0 ± 3.9 years, mean follow-up 3.5 ± 3.1 years, median 1.6 visits per year). Of these, 78% (n = 587) with MS and 11% (n = 31) with CIS received DMT before 18 years of age. This consisted of at least one newer DMT in 42%, including dimethyl fumarate (n = 102), natalizumab (n = 101), rituximab (n = 57), fingolimod (n = 37), daclizumab (n = 5), and teriflunomide (n = 3). Among 17%, the initial DMT prescribed was a newer agent (36 dimethyl fumarate, 30 natalizumab, 22 rituximab, 14 fingolimod, 2 teriflunomide). Over the last 10 years, the use of newer agents has increased, particularly in those ≥12 years and to lesser extent in those <12 years. The short-term side effect profiles of newer DMTs did not differ from those reported in adults.ConclusionNewer DMTs are often used in pediatric MS, and have similar short-term safety, tolerability, and side effect profiles as in adults. These findings may help inform pediatric MS management.

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The Ala/Ala genotype of PPARY Pro12 Ala polymorphism is associated with late onset of multiple sclerosis

Archives of Biological Sciences ◽

10.2298/abs1302447l ◽

2013 ◽

Vol 65 (2) ◽

pp. 447-453

Author(s):

N. Lukic ◽

A. Stankovic ◽

E. Dincic ◽

M. Bundalo ◽

Z. Krsmanovic ◽

...

Keyword(s):

Multiple Sclerosis ◽

Late Onset ◽

Age At Onset ◽

Peroxisome Proliferator ◽

Pro12ala Polymorphism ◽

Peroxisome Proliferator Activated Receptor ◽

Post Hoc ◽

Genotype And Allele Frequencies

The function of peroxisome proliferator-activated receptor ? (PPAR?) in immune regulation, as well as in antiinflammatory and anti-proliferative actions towards T lymphocytes, has been reported. A potential role of PPARs in multiple sclerosis (MS) was suggested. The aim of this study was to investigate if there is an association of PPAR?-2 Pro12Ala polymorphism with MS in 361 patients from Serbia. The genotype and allele frequencies of Pro12Ala polymorphism were not significantly different between controls and patients, or between females and males. In contrast to controls, we detected a rare Ala/Ala genotype in patients with MS. We found that there is a significant association of Ala/Ala genotype with older age at onset (ANOVA, p=0.07; LSD post-hoc, Ala/Ala vs. Pro/Ala, p=0.03, Ala/Ala vs. Pro/Pro p=0.02). It would be useful to validate our results in other populations, as well as to perform follow-up of the disease progression in regard to PPAR? genotypes.

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Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients

Multiple Sclerosis Journal ◽

10.1177/1352458512466317 ◽

2012 ◽

Vol 19 (7) ◽

pp. 941-946 ◽

Cited By ~ 91

Author(s):

Peter Huppke ◽

Kevin Rostasy ◽

Michael Karenfort ◽

Brenda Huppke ◽

Rainer Seidl ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Optic Neuritis ◽

Pediatric Patients ◽

Case Series ◽

Acute Disseminated Encephalomyelitis ◽

Oligoclonal Bands ◽

Central Nervous System Disorders ◽

Established Disease

Background: Some pediatric patients with inflammatory demyelinating central nervous system disorders cannot be classified under any of the established disease entities, making their treatment and prognosis difficult. Objective: The objective of this study is to characterize a subgroup of pediatric patients with recurrent demyelinating central nervous system disorders. Methods: This study includes a case series of pediatric patients with monophasic or recurrent acute disseminated encephalomyelitis (ADEM) who later presented with either monophasic or recurrent optic neuritis (ON). Results: We describe seven patients with a median follow-up of six years (five females, two males) who presented at a median age of 6 years (range 4–8 years) with monophasic ( n = 4) or recurrent ADEM (two to four attacks) followed by monophasic ( n = 3) or recurrent ON (two to nine attacks). Cranial magnetic resonance imaging (MRI) was typical for ADEM ( n = 6) with complete or almost complete resolution of lesions on follow-up. Cerebrospinal (CSF) studies at the time of ADEM showed a pleocytosis in six patients and were negative for oligoclonal bands (OCBs) in all. In all patients high titers for serum anti-MOG antibodies were detected. Conclusion: ADEM followed by ON is a rare but distinct clinical phenotype among pediatric patients. Further studies are needed to allow recommendations on treatment or prognosis.

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