Multiple Sclerosis In Children

Purpose
Long-term MRI follow-up of childhood-onset Relapsing/Remitting Multiple Sclerosis (RRMS) was carried out in 4 cases.

MRI findings were correlated with clinical course and characteristic differences from adult-onset RRMS were elaborated.

Methods
Two girls and one boy with true childhood-onset, and one girl with juvenile-onset RRMS underwent 5-16 MRI examinations within 6-8 years.

The total number of lesions, the numbers of new, active, disappearing and reappearing lesions, InfraTentorial and U-fiber lesions, "giant" plaques and "black holes" were counted.

Callosal Atrophy and general Brain Atrophy were assessed. The findings were related to the physical status according to the Expanded Disability Status Scale (EDSS).

Results And Conclusions
Results showed that the primary differences in childhood-onset RRMS compared to adult-onset RRMS lie in the lack of, or slower development of irreversible changes ("Black Hole" formation, Brain Atrophy).

Despite Callosal Atrophy and intensive U-fiber region involvement, school performance was unchanged.

Regarding the frequency of "giant" Lesions, an even more pronounced White Matter involvement was found in our children compared to adults. All children exhibited a rather "Benign" disease course.

A more intensive ReMyelination, less severe Neuronal loss, and higher Functional Brain Plasticity at younger ages may account for these differences.

Introduction
The secondary Encephalitis Disorders are due to an Immunological mechanism which causes DeMyelinating lesions of the Central and Peripheral Nervous Systems, with very variable clinical features.

The PathoGenesis and localization of Benign Encephalitis of the BrainStem and the Miller Fisher Syndrome (MFS) are still subject to debate.

It is suggested that they may both belong to different extremes of the same nosological spectrum known as the Ophthalmoplegia-Ataxia-Areflexia Syndrome.

Clinical Case
We report the case of an 11 year old boy with Encephalitis of the BrainStem who had electromyographic alterations compatible with the Guillain Barre Syndrome, and MR images characteristic of an acute DeMyelinating Disorder of the BrainStem.

Conclusions
The Encephalitis of the BrainStem is an uncommon condition in children which leads to diagnostic difficulty at its onset.

Since this is similar in other disorders such as MFS, Tumors, CerebroVascular accidents and less often in the initial stages of Multiple Sclerosis.

The clinical course is very useful to distinguish between these conditions. MR is the imaging technique of choice for diagnosis in these patients.

Although there is currently no specific treatment for Post-Infectious Encephalitis, the use of high doses of ImmunoGlobulins may be justified in view of the PhysioPathological origin of the condition.

The prognostic factors for relapse of the initial MRI findings after a first episode of acute CNS Inflammatory DeMyelination are unclear in children.

In this study we aimed to identify initial MRI factors that are predictive of a second attack and disability after a first episode of acute CNS Inflammatory DeMyelination in childhood.

A cohort of 116 children who had a first episode of acute CNS Inflammatory DeMyelination between 1990 and 2002 was studied using survival analysis methods.

The initial MRI data were reviewed in a systematic, standardized, double-blind manner. The average follow-up was 4.9 +/- 3 years.

Multivariate analysis showed that the rate of second attack was higher in patients with Corpus Callosum long axis perpendicular lesions (34 out of 116 patients, 30%) on the initial MRI [Hazard Ratio (HR) 2.89;

95% confidence interval (CI) 1.65-5.06] and/or with the sole presence of well-defined lesions (46 out of 116 patients, 40%) (HR 1.71; 95% CI 1.29-2.27).

Both criteria were more specific predictors (100%) of relapse, demonstrating conversion to Multiple Sclerosis, than the three Barkhof Criteria (63%).

But were less sensitive (21% compared with 52%). None of the MRI criteria was predictive of severe disability.

Using initial MRI and survival analysis methods, we identified two specific predictors of relapse and conversion to Multiple Sclerosis.

After a first episode of acute CNS Inflammatory DeMyelination in childhood. Their low sensitivity, however, shows that this prediction remains difficult.

Although Psychological distress and Cognitive Dysfunction are well documented in adults with Multiple Sclerosis (MS), they are poorly understood in children with the disease.

PsychoSocial difficulty experienced by children and adolescents with MS involves factors common to all chronic illnesses in children, as well as MS-specific factors.

The PsychoSocial manifestations of the disease may affect the patient's self-image, role functioning, mood, and Cognition to adversely affect schooling, interpersonal relationships, and treatment compliance.

Furthermore, the impact of having a family member with MS may affect overall family functioning.

Assessment and interventions for PsychoSocial and Cognitive problems in pediatric MS should be multidisciplinary in nature and address the child's functioning at home, school, and among peers, as well as the effect on the family.

Studies in adult patients with Multiple Sclerosis (MS) suggest significant benefit of early treatment initiation.

However, there are no approved therapies for children and adolescents with MS.

For adult MS, tolerability and efficacy of several ImmunoModulatory and ImmunoSuppressive drugs have been demonstrated. Guidelines for the use of these MS therapies in children do not exist.

Several small cohort studies of the safety and tolerability of Disease-Modifying Therapies (DMTs) in children and adolescents with MS have been recently reported.

The side effects of Interferon-beta (IFN-ß) and Glatiramer Acetate (GA) appear to be similar to those reported by adults.

The long-term tolerability and safety have yet to be established and efficacy data have yet to be studied.

In view of the potential for significant long-term physical and Cognitive disability in children with MS, and recent evidence that initiation of ImmunoModulatory therapy early in the course of MS improves long-term prognosis.

An increasing number of children and adolescents with MS are being offered the DMTs approved for adults.

This review summarizes current knowledge of DMTs in pediatric MS and experience in several centers treating pediatric MS and MS variants.

Such as NeuroMyelitis Optica (Devic Disease), Balo's Concentric Sclerosis, Marburg acute MS, and Schilder Disease (MyelinoClastic Diffuse Sclerosis).

Finally, an overview of symptomatic MS therapies and experiences with these treatments in pediatric patients is provided.