'Scanning Speech' has been used as a description of a prominent characteristic of the Dysarthria of Multiple Sclerosis (MS) as well as of Ataxic Dysarthria in general.

It is thought to be measurable as equalized Syllable durations.

There are seemingly contradictory Prosodic-Temporal characteristics of Ataxic Dysarthria: perceptually characterized as Prosodic excess as well as Phonatory-Prosodic insufficiency and Acoustic characteristics including signs of IsoChrony as well as variability.

This study investigates the temporal characteristics at two levels, duration and variability of Syllable durations and the durations of InterStress Intervals.

A group of 14 individuals with MS and Ataxic Dysarthria as well as 15 control subjects were studied. It was concluded that individuals with Ataxic Dysarthria and MS showed:

1. For Syllables: significantly increased durations and decreased IntraUtterance variability (more IsoChrony or Syllable equalization) as well as significantly increased InterUtterance variability;

2. For InterStress Intervals: significantly increased durations and increased variability (less IsoChrony).

The results point to inflexibility as well as instability of Temporal control, which could contribute to the explanation of why the perceptual characteristics are contradictory.

Copyright 2000 S. Karger AG, Basel

In this study, we evaluated the correlation between NeuroPsychological Impairment (measured with the Brief Repeatable Battery NeuroPsychological Tests).

And JuxtaCortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to Spin-Echo MRI sequences in detecting JuxtaCortical MS lesions.

A total of 39 patients with Definite MS were evaluated by MRI with a conventional and fast Spin Echo sequence and fast-FLAIR sequence.

And NeuroPsychological tests of the Brief Repeatable Battery NeuroPsychological tests were performed. The Z-score of all subtests were used to calculate a Cognitive Impairment Index.

The results show that a high number of JuxtaCortical lesions is detected with thin slice FLAIR (30% of all lesions seen). This percentage was not superior to Spin-Echo, reflecting the thin slice thickness (3 mm) we used.

The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques.

While the number of Non-Cortical lesions correlated with the Expanded Disability Status Scale (r=0.32, P=0.045), the number of JuxtaCortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index.

Our study underlines the high number of JuxtaCortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI.

It also stresses the importance of JuxtaCortical lesions on determining NeuroPsychological Impairment.

Multiple Sclerosis (2000) 6 280 - 285

In a randomized, placebo-controlled, double-blind study, Glatiramer Acetate (Copaxone(R)) reduced the relapse rate and slowed accumulation of disability for patients with Relapsing/Remitting Multiple Sclerosis.

Of the original 251 patients randomized to receive Glatiramer Acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug.

The majority of the original double-blind cohort continues to receive Glatiramer Acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse.

The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg Glatiramer Acetate were well tolerated.

The mean annual relapse rate of the patients who received Glatiramer Acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 - 0.51). The rate per year has continued to drop and for the sixth year is 0.23.

Of the group who have received Glatiramer Acetate without interruption for 5 or more years, 69.3% were Neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS).

Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out.

This study demonstrates the sustained efficacy of Glatiramer Acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with Relapsing forms of Multiple Sclerosis.

Multiple Sclerosis (2000) 6 255 - 266

A comprehensive set of 31 Binocular NeuroPsychological tasks assessing a series of Spatial and Non-Spatial VisuoPerceptual abilities was used to study VisuoPerceptual Impairment.

In a representative group of 49 MS-clinic patients exhibiting neither diagnosed Ophthalmological afflictions nor major Psychiatric diagnoses.

Among these patients, true frequency rate of VisuoPerceptual Impairment, i.e. of subjects failing four or more tasks, was estimated at 26%.

The pattern of VisuoPerceptual Impairment was non-uniform, non-selective, restricted and idiosyncratic. Only four tasks yielded significant rates of impairment.

They concerned Color Discrimination, the perception of the Muller-Lyer illusion and Object Recognition in two separate conditions.

Each of the four factors identified by factor analysis had an important representative (with factor loading >0.35) among these four tasks. Failures on these tasks correlated poorly.

Together, the four tasks satisfactorily predicted VisuoPerceptual Impairment as defined by the comprehensive set of tasks (sensitivity 86.7%; specificity 81.3%), but with regard to an uncontaminated criterion, their aggregate sensitivity and specificity was only 75 and 56% respectively.

VisuoPerceptual NeuroPsychological task performance related significantly but weakly to Cognitive Status, Physical Disability and to Pyramidal, Cerebellar and BrainStem Neurological Signs.

And did not correlate with other clinical Neurological Signs, disease duration, type of MS, a history of Optic Neuritis, Depression or medication status.

Multiple Sclerosis (2000) 6 241 - 254

Sp3 belongs to a large family of transcription factors that bind GC/T box elements. We have previously demonstrated the deficient expression of Sp3 in Peripheral Blood MonoNuclear Cells (PBMC) from most patients with Multiple Sclerosis (MS).

In the current study, the Sp3 Gene was assigned to Chromosome 7 by using somatic cell hybrid mapping and analysis of a Chromosome 7-specific cosmid library. The position of Sp3 was refined to 7p14-p15.2 by fluorescence in situ hybridization (FISH).

Southern blot and polymerase chain reaction analysis of Genomic DNA failed to demonstrate a detectable difference between MS and control PBMC.

Spontaneous Sinusoidal Oscillations of the eyes are a feature of disorders affecting Central Myelin, including Multiple Sclerosis. The mechanism responsible for these Oscillations (Pendular Nystagmus) is unknown.

We tested the hypothesis that Pendular Nystagmus is due to instability of the Neural integrator, a network of Neurons that normally guarantees steady gaze by mathematically integrating PreMotor signals.

It was possible to make a model of the Neural integrator unstable, and abnormal feedback then produced sustained Oscillations so that it simulated Pendular Nystagmus.

One prediction of the model is that a large PreMotor signal, such as is required to generate a rapid (Saccadic) eye movement, will transiently suppress the activity of some Neurons in the network, and that this will "reset" the Oscillations, i.e., produce a phase shift; larger Saccades will produce greater phase shifts.

Alternatively, if the source of Pendular Nystagmus is outside the Neural integrator (i.e., is present on velocity inputs to the stable integrator), then it may not be possible to reset the Oscillations with a Saccadic Eye movement.

We compared the phase relationships of Pendular Nystagmus prior to and following Saccades in six patients with Multiple Sclerosis (MS).

All patients showed phase shifts (median 64 degrees) of their Ocular Oscillations following large (more than 10 degrees) Saccades; smaller Saccades (less than 5 degrees) caused smaller phase shifts (median 17 degrees).

Our findings suggest that, in MS, Pendular Nystagmus arises from an instability in the feedback control of the Neural integrator for Eye movements, which depends on a distributed network of Neurons in the BrainStem and Cerebellum.

Objectives
Body cooling has been proposed as a symptomatic treatment for Multiple Sclerosis.

This study aimed to assess the effects of body cooling and of Circadian variations on clinical parameters and on Visual and Auditory Evoked Potential measures in Multiple Sclerosis patients.

Methods
Clinical status was assessed and VEPs, BAEPs and MLAEPs (all with two stimulus frequencies) were recorded a total of 4 times on two separate days (two times per day at 08:30 and 15:00 h each day) in 10 Multiple Sclerosis patients and 10 controls.

On one of these days, the subjects were submitted to body cooling before the afternoon session.

Results
Tympanic temperature was significantly higher in the afternoon. Cooling lowered the temperature by 1.4 degrees C. No clinical effects were observed.

Circadian effects were detected on VEP amplitude, which increased both in controls and in patients at low stimulus frequency (P<0.01), and increased in controls and decreased in patients at high stimulus frequency (interaction: P<0.01).

Cooling determined an increase in BAEP I-V peak-to-peak time in controls, and a reduction in patients at high stimulus frequency (interaction: P<0.01).

In patients, cooling also determined a great increase in MLAEP amplitude (interaction: P<0.001). We did not find cooling effects on VEP measures.

Conclusions
Visual and Auditory Evoked Potentials showed differences in Circadian and cooling effects between controls and Multiple Sclerosis patients.

These differences are consistent with the hypothesis of Temperature-dependent Conduction Blocks in DeMyelinated fibers. Cooling may have a clinical effect in selected patients only.

Methods
The prevalence of AntiBodies against Herpes Simplex Virus type 1 (HSV-1), HSV-2, EBV, and CytoMegaloVirus was determined in a group of 108 MS patients and in 163 healthy control subjects.

Sera were analyzed using combinations of novel assay systems employing highly purified Viral and recombinant Antigens. In addition, PCR for the detection of EBV DNA was performed in serial samples.

Results
In contrast to the control populations, AntiBodies against EBV were present in 100% of MS patients. Among the tested Human HerpesViruses, this high extent of seropositivity was only found for EBV.

Primary infection was found exclusively in the control group (3.7%), whereas serologic evidence of EBV reactivation was seen in MS patients (13.9%) as well as control subjects (17.2%).

There was no temporal coincidence between EBV reactivation and disease activity in MS patients.

However, in 19 patients followed monthly for 1 year, active Viral replication as measured by increased ImmunoGlobulin (Ig) M and IgA responses to EBV early Antigens (p54 + p138).

Positive Serum DNA was seen in 72.7% of patients with exacerbations during the study period and in none of the patients with clinically stable disease.

Conclusions
The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.

There is a lack of precise data concerning the natural history of Cognitive Disorders in Multiple Sclerosis (MS), but recent NeuroPsychological studies have demonstrated that the incidence of such disorders in MS appears to be frequent (40-65% of cases).

And have shown in particular that Recent Memory, Conceptual Reasoning, Attention, Executive Functions, VisuoSpatial Perception and Information Processing Speed are negatively affected.

In contrast, language functions, general intelligence and Implicit Memory appear to be relatively well preserved.

Although the presence and the degree of Cognitive Disorders does not seem to be directly linked to disease duration or to the extent of physical Disability, the relationship between Cognitive decline and Brain lesions detected by Magnetic Resonance Imaging (MRI) is still a subject of discussion.

The prevalence of Emotional and Affective Disorders is difficult to estimate.

Their frequency has only rarely been investigated, and the lack of data on the natural history of these disorders and those factors which they have in common (the PsychoSocial consequences of this chronic and disabling disease, Cognitive Impairment, and Brain lesions) further complicate the determination of treatment strategy.

The adoption of appropriate strategies could limit the negative impact of this disease on the social functioning of MS patients.

It is unclear whether Brain MRI lesions are associated with Depression in Multiple Sclerosis (MS).

Neurological dysfunction in Depressed (n= 19) and non-Depressed (n = 29) MS patients was rated by Expanded Disability Status Scale (EDSS). EDSS was weakly predictive of the presence of (p = 0.03) and severity of (p = 0.01) Depression.

After correcting for EDSS, the presence of Depression was predicted by Superior Frontal and Superior Parietal HypoIntense T₁ lesions (p<0.01);

The severity of Depression was predicted by Superior Frontal, Superior Parietal and Temporal T₁ lesions, Lateral and Third Ventricular enlargement, and Frontal Atrophy (p<0.01).

Depression was not related to bright T₂ lesions or enhancement.

We conclude that Atrophy and Cortical-SubCortical disconnection due to Frontal and Parietal White Matter destructive lesions may contribute to Depression in MS.