MS Abstracts 03e-2g1

Plasma exchange has not been widely accepted as a treatment for Multiple Sclerosis. However, several uncontrolled studies have suggested that patients with severe attacks of MS and other inflammatory DeMyelinating Disease may improve rapidly after Plasma exchange treatment.

We recently completed a randomized, sham-controlled, crossover clinical trial of Plasma exchange in 22 patients with idiopathic inflammatory DeMyelinating diseases of the Central Nervous System.

Twelve had MS and ten had other inflammatory DeMyelinating disease syndromes.

Forty-two percent of patients experienced moderate or greater recovery over 2 weeks of active treatment administered every other day while only 6% of patients experienced similar improvement while receiving sham treatment.

Three patients who failed the sham treatment subsequently improved rapidly after crossover to active treatment; no patient who failed active treatment improved after crossover to sham.

This study illustrates the importance of designing randomized clinical trials based on the treatment regimen and patient population studied in the uncontrolled reports that suggested treatment efficacy.

Plasma exchange should be considered for patients with idiopathic inflammatory DeMyelinating disease syndromes when they have failed CorticoSteroid therapy.

J. Clin. Apheresis. 16:39-42, 2001. Copyright 2001 Wiley-Liss, Inc.

The Paced Auditory Serial Addition Test (PASAT) is a commonly used procedure that combines elements of both a working memory task and a test of information processing speed.

Patients with Multiple Sclerosis (MS) have consistently been found to be impaired on this test and it has been recommended as a core outcome measure in clinical trials.

The standard score for this task is the number of correct responses at each stimulus presentation rate.

But a concern has been raised that subjects may ignore some test items in order to chunk the information into manageable portions and avoid performing several Cognitive tasks simultaneously.

To account for this strategy, one can examine the proportion of correct responses that are consecutive (termed dyads), since such responses require that the task be performed according to the instructions.

We compared a group of 35 mildly to moderately disabled MS patients and matched healthy controls on the PASAT.

The MS patients made significantly fewer correct responses at the 2 slowest presentation rates (2.4, 2.0 s/digit) while their scores at faster rates (1.6, 1.2 s/digit) did not discriminate them from controls as well.

Nevertheless, the MS patients' percentage of dyads was significantly lower than that of the control sample across all stimulus presentation rates.

While our study supports the use of the PASAT as a test that distinguishes MS patients from healthy individuals, our results also illustrate problems that lie in the interpretation of this difference in performance.

It appears that a chunking strategy may be common in the PASAT, particularly as task demands increase, and that this may mask actual performance differences.

If so, the total correct response score alone is limited as a measure of working memory and information processing speed.

More detailed analyzes of PASAT performance, coupled with other measures of information processing, may help clarify the underlying Cognitive deficits of MS patients.

Deficits in tasks measuring Visual processing have been earlier reported in studies of MS. Yet, the nature and severity of Visual-processing deficits in MS remains unclear.

We used a new method in order to measure the different stages of Visual processing in object recognition: shape recognition, familiarity recognition, semantic categorization, and identification with naming.

Six two-choice reaction-time tasks were presented to 30 MS patients and 15 healthy controls. The patients were divided into cognitively preserved and Cognitively deteriorated study groups according to their Cognitive status.

The purpose was to find out whether deficits at specific stages of Visual processing can be found in Cognitively deteriorated MS patients.

Cognitively deteriorated MS patients did not perform as well as Cognitively preserved MS patients or healthy controls.

They were slower already at the early stage of Visual processing where discrimination of whole objects from scrambled ones was required. They also had higher error rates in tasks requiring object familiarity detection and object identification with naming.

Thus, Cognitively deteriorated MS patients had difficulties in visual shape recognition and semantic-lexical processing.

However, variation of performances was large within both of the patient groups indicating that even patients without a generalized Cognitive decline may have deficits in some stages of the visual processing.

We suggest that because of the heterogeneity of the patients, every single case needs to be examined separately in order to identify the possible deficits in Visual processing.

HHV-6 is an opportunistic Viral pathogen that has been demonstrated as the cause of often life-threatening illness in pediatric patients and transplant recipients.

A substantial body of scientific evidence links HHV-6 to the etiology of such chronic diseases as Multiple Sclerosis. For these reasons, it is important that patients in these groups be screened for possible infection with HHV-6.

Serological studies for IgG and/or IgM can be misleading, as are PCR analyzes, which cannot distinguish between latent and actively replicating virus. Currently, the only reliable method for diagnosing an active infection with HHV-6 is Viral isolation.

Thirty-one patients were followed-up, at 3-month intervals for the first year and at 6-month intervals for the second year, after an episode of Optic Neuritis. The object was to confirm previous evidence for a progressive shortening of Visual Evoked Potential (VEP) latencies.

And to determine whether this is associated with any change in the clinical Ocular examination, visual fields or contrast sensitivity.

VEP latencies were found to decrease significantly during both the first and (less strikingly) the second year, the most marked changes occurring between 3 and 6 months.

Contrast sensitivity improved during the first 9 months, but subsequently tended (non-significantly) to deteriorate.

A similarly transient improvement in central visual field sensitivity was seen in a subgroup of patients with clinically overt Multiple Sclerosis.

In the data from the acutely unaffected fellow eyes, no significant changes in VEP parameters or functional indices were observed.

The findings extend those of a previous study which showed significant shortening of VEP latencies between 6 months and 3 years without significant functional improvement.

Over this period, a significant prolongation of VEP latencies occurred in the asymptomatic fellow eye, accompanied by contrast sensitivity deterioration.

Taken in conjunction, the two studies suggest that recovery processes involving ReMyelination or, possibly, ion channel reorganization proceed for at least 2 years.

The concurrent effects of insidious DeMyelination and/or Axonal degeneration (also occurring in the fellow Optic Nerve) are initially masked by the recovery process, but gradually become more evident.

The functional benefits of the long-term recovery process are relatively minor and are usually reversed within a few years.

Nevertheless, it is suggested that long-term ReMyelination may perform an important role in protecting DeMyelinated Axons from degeneration.

Understanding the factors which promote long-term ReMyelination may have significant implications for therapy in Multiple Sclerosis.

Objective
We tested the hypothesis that the Plasma level of Endothelin-1 (ET-1) is increased in patients with Multiple Sclerosis (MS).

The peptide ET-1 is one of the most potent known Vasoconstrictors. An increased level of Endothelin could explain some of the Vascular symptoms of these patients.

Materials And Methods
A specific radioimmunoassay was used to determine ET-1 Plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects.

Results
The Plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005).

The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers.

Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease.

Conclusions
The Plasma ET-1 level is markedly and significantly increased in patients with MS. Neither the cause of such an increase nor the PathoGenetic role is known.

We report on a 10-year old previously healthy boy who exhibited a fulminant and nearly monophasic clinical course of DeMyelinating Encephalitis with Relapsing IntraCranial Hypertension Syndrome.

Histologic examination of a diagnostic Brain biopsy revealed an inflammatory DeMyelinating process with PeriVascular T-Lymphocytic infiltration and Axonal damage reminiscent of Multiple Sclerosis-like lesions. In the Brain, the DNA of Human Herpes Virus 6 (HHV6) was detectable.

Eleven months after the initial symptoms and on maintainance with oral Steroids, MRI showed DeMyelination of both Hemispheres as well as DeMyelination of the BrainStem and Wallerian Degeneration. The boy exhibited a severe Neurologic defect syndrome.

The clinical and radiological course is unusual because of the asymmetric progression of the Encephalitis and the extensive confluent lesions without demarcated border or enhancement of the rim after injection of Gadolinium.

The clinical course showed no definite Steroid response.

The PathoGenetic relevance of HHV6 remains elusive. Although single patients with HHV6-associated EncephaloMyelitis have been reported, HHV6 DNA is occasionally detected in Brains of healthy individuals.