HemiDystonia is usually associated with a structural lesion in the ContraLateral Basal Ganglia. We report a patient with definite Multiple Sclerosis, according to Poser's Criteria, presenting with an acute-onset sustained left HemiDystonia.

Cranial T₂-weighted Magentic Resonance Imaging (MRI) showed several HyperIntense lesions in the Centri Semiovali and in the PeriVentricular area without Basal Ganglia involvement.

Moreover Cervical spinal cord T₂-weighted MRI showed two HyperIntense lesions in the left PosteroLateral Spine at C2 and C3, and one lesion in the right PosteroLateral Spine at C4 levels.

The HemiDystonia improved completely after daily treatment with 1000 mg of MethylPrednisolone, and Cervical MRI was performed after the improvement which showed that the lesions had become smaller and less intense.

Finally we consider that the HemiDystonia may be caused by the Cervical Spinal Cord lesions of Multiple Sclerosis.

We present a case of Paroxysmal HemiDystonia in a patient with an isolated DeMyelinating lesion in the SubThalamic region, involving the Posterior Arm of the Internal Capsule and extending to the SubThalamic Nucleus and MesenCephalon, possibly due to Multiple Sclerosis.

Compared with similar reports in the literature, in our case there was a paucity of lesions, permitting a more direct clinico-anatomical correlation.

The role of the SubThalamic region and Basal Ganglia circuitry in the Genesis of symptomatic Dystonia is discussed.

Background
Major Depression affects one in two patients with Multiple Sclerosis (MS) during the course of their lifetime. This adds to the morbidity associated with the disorder and may contribute to an increased mortality rate because of suicide.

Over the past few years, with the advent of disease modifying treatments for MS, a new concern with respect to Mood has arisen, namely the possibility that some of these drugs may have Depression as a clinically significant side effect.

Objective
To ascertain whether disease modifying treatments in MS are associated with the development of Depression or the worsening of a depressive illness.

Methodology
A MEDLINE and PSYCHLIT search focusing on Depression and disease modifying treatments going back to 1993 (the publication date of the results of the first randomized, placebo controlled trial).

The methodology pertaining to the assessment of Depression is critically reviewed. Furthermore, a critical summary is provided of treatment modalities for the Depressed MS patient.

Results
There are conflicting data that Depression may occur with some disease modifying drugs, particularly Interferon-ß-1b.

However, all studies reveal limitations with respect to the assessment of Mood. Some reports, despite omitting details of how mentation was assessed, still comment on the presence or absence of Depression.

Others suffer from one or more of the following shortcomings: a failure to assess premorbid risk factors for Mood Disorder; a reliance on one question to assess Depression; the utilisation of self report Mood Rating Scales of questionable validity; neglecting to distinguish Depression as a symptom from Depression as a Syndrome (i.e. Major Depression as defined by the DMS-1V).

Conclusions
Given the many methodological pitfalls inherent in all studies to date, it is premature to conclude that disease modifying drugs are associated with Depression.

Evidence suggests that treatment of Depression, irrespective of a putative association with a disease modifying agent, is frequently effective.

This applies to PharmacoTherapy or PsychoTherapy, although the former may be preferred should Depression arise during a course of treatment with a disease modifying agent.

Multiple Sclerosis (2000) 6 343 - 348

Gene therapy traditionally has been associated with "gene replacement." where exogenous recombinant DNA is introduced ex vivo into Somatic Cells that are then introduced back into the patient as a way to correct an inherited Genetic defect.

However, several novel Gene therapy strategies for treating AutoImmune Diseases recently have emerged.

Strategies involving the use of several types of DNA vaccines, the application of various Viral vectors, and the use of diverse cellular vectors have shown promise in inhibiting AutoImmune-mediated inflammation and repairing tissue damaged as a result of AutoImmune attack.

In the current review, we examine and discuss the development and proposed use of emerging Gene therapy strategies for the treatment of AutoImmune Disease.

With specific emphasis on Experimental AutoImmune EncephaloMyelitis (EAE), an animal model widely used in Multiple Sclerosis (MS) research.

Objective
To determine whether Cognitive Fatigue, defined as a decline in Cognitive performance over a single testing session, could be identified in MS.

Methods
Forty-five individuals with MS and 14 healthy control participants completed a 4-hour session of Cognitive testing.

That involved a baseline NeuroPsychological Battery, a continuous effortful Cognitive task (completing mental arithmetic problems administered on a computer), and a repeat NeuroPsychological Battery.

Self-report measures of Fatigue and Affect were completed before each step of the testing session.

Results
The pattern of change in Cognitive performances over the testing session significantly differed between the MS and control participants.

Individuals with MS showed declines on measures of Verbal Memory and Conceptual Planning, whereas the control participants showed improvement.

There were no significant differences between the groups on any of the baseline Cognitive measures/P>

The MS participants performed worse than the control subjects on tests of Visual Memory, Verbal Memory, and Verbal Fluency that were repeated following the continuous effortful Cognitive task.

Both MS and control participants reported increased mental and physical Fatigue across the testing session compared with their baseline values.

Conclusion
Individuals with MS show declines in Cognitive performance during a single testing session and fail to show the improvement exemplified by healthy control subjects.

Recently there have been considerable advances made in the treatment of Multiple Sclerosis.

For the first time since its initial clinical description in the 1800s, there are now available several medications which unequivocally exert favorable clinical effects, through the lowering of the biological activity of the human illness.

The therapeutic efficacy of IFN-ß preparations seems particularly well established in this regard on the basis of five large, independent, trials of this agent.

These trials have demonstrated remarkably consistent reductions in both attack rates and disability levels using a combination of clinical and Magnetic Resonance Imaging outcome measures.

The therapeutic benefit of Glatiramer Acetate also has been well established, although there is less available data on this agent than there is for Interferon.

It is important to recognize, however, that, although these agents represent an important first step in the management of patients with Multiple Sclerosis, they are only partial therapies.

In order to actually cure the illness or even to substantially improve patient outcome we need considerably better agents than we have currently.

Nevertheless, it is likely that, with improved knowledge of the role that Interferon-ß plays in the PathoGenesis of Multiple Sclerosis and with better understanding of the mechanism by which Glatiramer Acetate exerts its therapeutic effect, greatly improved therapeutic agents will be available in the future.

In addition, it seems likely that, in the future (by analogy to the experience in oncology), we will begin utilising combinations of therapies in order to better control the biological activity of this debilitating disease.

Such combination therapy will almost certainly include combinations of partially effective agents as well as combinations of these agents with other medications (e.g., the ImmunoSuppressive drugs) which, by themselves, have only been demonstrated to exert marginal clinical benefits on the course of illness.

Moreover, it also seems likely that, increasingly, therapeutic strategies that enhance or promote Myelin repair will become a major focus of clinical research in this area.

Background
Fas (CD95) triggers programmed cell death and is involved in shutting off the Immune Response. Inherited deleterious mutations hitting Fas or its signaling pathway cause AutoImmune LymphoProliferative Syndrome (ALPS).

Objective
To assess the possibility that decreased Fas function plays a role in development of MS.

Methods
The authors evaluated Fas function in long-term T-Cell lines (21 days of culture) from 32 patients with Relapsing/Remitting MS (RR/MS), 15 with Secondary/Progressive MS (SPMS), and 15 with Primary/Progressive MS (PP/MS) by assessing cell survival upon Fas triggering by MonoClonal AntiBodies (Mab).

Results
Fas-induced cell death was significantly lower in all patient groups than in controls, and lower in SP/MS than in RR/MS.

Moreover, 8/15 patients with PP/MS, 10/15 with SP/MS, and 8/32 with RR/MS were frankly resistant to Fas.

Frequency of resistance to Fas-induced cell death was significantly higher in all patient groups than in controls (2/75), and higher in SP/MS than in RR/MS.

The findings that the parents of two Fas-resistant patients were Fas-resistant and that fusion of T-Cells from two Fas-resistant patients with Fas-sensitive HUT78 cells gave rise to Fas-resistant hybrid lines.

Suggest that Fas-resistance is due to inherited alterations of the Fas signaling pathway, with production of molecules exerting a dominant negative effect on a normal Fas system.

Conclusions
Defects of the Immune Response shutting-off system may be involved in the PathoGenesis of MS, particularly in its progressive evolution.

The specific aim of this study was to determine whether progressive Brain atrophy could be detected within 18 months of establishing a diagnosis of Relapsing/Remitting Multiple Sclerosis (RRMS).

Fifteen patients with clinically definite RRMS (mean disease duration from first symptom=6 months, mean EDSS=1.2) completed 6 - 14 monthly quantitative MRI sessions.

The volume of the Lateral Ventricles was determined each month using a semi-automated thresholding technique from T₁-weighted axial images.

The number of new monthly Gadolinium-enhancing (Gd⁺) lesions and EDSS scores were also recorded. Lateral Ventricular volumes increased significantly during this study.

When individual data were examined, statistically significant changes were observed in six of 15 patients. Monthly change in Ventricular volume was related to baseline EDSS and total number of new Gd⁺ lesions.

These observations indicate Brain atrophy, a putative imaging marker of diffuse DeMyelination and Axonal loss, can occur as early as 18 months after first symptons of RRMS, and is related to the baseline level of disability and to the number of new Gd⁺ lesions.

Multiple Sclerosis (2000) 6 332 - 337

Objectives
To determine the quality of life (QoL) of MS patients during the initial 6 months of treatment with Interferon-ß (IFN-ß).

Furthermore, to determine whether changes in QoL relate to disability, emotional state, therapeutic expectations or side effect profile.

Background
IFN-ß has been shown to have beneficial effects on the course of MS.

Since the aim of IFN-ß treatment is not to cure but to slow down the disease it is important to know how this treatment affects QoL.

Surprisingly, the impact of treatment with IFN-ß on QoL measures has not been extensively studied so far.

Methods
Case report documentation, including EDSS, SF-36 and MADRAS scores, of 51 Relapsing/Remitting MS patients treated with IFN-ß was obtained at baseline and at months 1, 3 and 6.

Patients also filled in a form about their expectations of therapy and a questionnaire on side effects.

Results
During treatment there was a significant linear trend indicating improvement in the Role-Physical Functioning (RPF) scale of the SF-36 (F1,50=4.9, P=0.032).

A transient decrease at month 1 was found in the scale for bodily pain, indicating more experienced pain (F1,50=19.8, P<0.001).

Subgroup analysis showed that patients with most depressive symptoms on the MADRAS at baseline contributed most to the increase in RPF scores over time (F1,24=5,6 P=0.026).

Furthermore, we found associations between adverse event scores and several domains of QoL.

Conclusions
Our findings suggest that IFN-ß therapy has an impact on QoL of MS patients in that it improves role-physical functioning and transiently worsens experienced bodily pain.

QoL during treatment with IFN-ß is influenced by depressive symptoms at baseline as well as by treatment-associated side-effects.

Multiple Sclerosis (2000) 6 338 - 342