MS Abstracts 03b-2g5

Trigeminal involvement detected by Magnetic Resonance Imaging (MRI) in Multiple Sclerosis (MS) patients is usually associated with Trigeminal Neuralgia (TN) or painless Paresthesia in the Trigeminal distribution.

Our aim is to review the incidence of Trigeminal involvement on MRI in a series of patients with MS at our institution, with further clinical correlation.

We reviewed MRI scans of 275 MS patients for the presence of Gadolinium enhancement on postcontrast T₁-weighted images, anatomical and signal abnormalities on different sequences at the Pontine Trigeminal Root Entry Zone (REZ) and in the Cisternal portion of the Nerves.

We observed enhancement in the Cisternal portion of the Nerves and signal abnormalities (with or without enhancement) at the Pontine Trigeminal REZ in 8 (2.9%) patients, and enhancement was BiLateral in 6 (75%) of those.

Despite the inflammatory activity, none of them had TN and 3 (37.5%) had only painless Paresthesia in the correspondent V3 distribution. We also found a marked Trigeminal Hypertrophy in 2 (25%) patients, both with a longer period of disease.

Our results confirm a high and clinically silent incidence of Trigeminal involvement in MS patients, and suggest a simultaneous role of the Central and Peripheral type of Myelin in Trigeminal DeMyelination.

Objective
The Human Herpesvirus Type-6 (HHV-6) has been implicated in Multiple Sclerosis (MS). ValAcyclovir is an AntiViral agent with an excellent safety profile.

A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with ValAcyclovir would be safe and (2) observe if ValAcyclovir would delay the progression of MS clinically or by Magnetic Resonance Imaging (MRI).

Design/Methods
Fifty-eight patients were stratified as to severity and randomly assigned to receive ValAcyclovir (3000 mg/day) or placebo for a period of two years.

Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and Brain MRI scans.

Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations.

Results
No patient discontinued the study due to side effects or toxicity.

In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect.

Conclusions
Although not statistically significant, positive trends were detected for Acyclovir by clinical measures, but not by MRI.

Objective
To examine the safety of combination therapy with Mitoxantrone (MITX) and Interferon-ß-1b (IFN-ß-1b) in patients with Multiple Sclerosis (MS) and a high on-therapy relapse rate and enhancing lesions on baseline Magnetic Resonance Imaging (MRI) scan.

Methods
Ten patients with worsening Relapsing/Remitting or Secondary/Progressive MS were studied using monthly MRI with triple-dose Gadolinium contrast.

All patients must have been on IFN-ß-1b for at least six months, have at least one enhancing lesion on a screening MRI, at least one relapse on IFN-ß-1b in the six months prior to study entry and be Neutralizing AntiBody negative.

Monthly MRI scans using triple dose contrast and a 30-minute delay between contrast administration and scanning were carried out three times over two months to obtain baseline numbers of enhancing lesions each month.

At the end of the baseline phase, MITX was administered at 12 mg/m2 (month 3), and 5 mg/m2 at months 4 and 5. Dosing was continued at 5 mg/m2 every third month. Monthly MRI scanning was continued throughout the duration of MITX dosing.

The primary outcome measure was the frequency of new enhancing lesions. Secondary outcome measures included relapse rate, and T₁ HypoIntense and T₂ lesion burden.

Results
Following the addition of MITX to IFN-ß-1b mean enhancing lesion frequency decreased 90% at month 7 (P = 0.008) and enhancing lesion volume decreased by 96% (P = 0.01). Relapse rates decreased 64% (P = 0.004).

T₂ lesion burden and T₁ HypoIntense lesion burden increased slightly during the baseline phase and decreased following MITX but the difference did not reach statistical significance.

There were no serious adverse events on combination therapy and no drop-outs due to toxicity.

Total white blood cell count was reduced at 14 days post-MITX infusion but returned to normal levels by day 21. There were no neutropenic fevers and there was no clinically significant elevation of Liver function tests.

Conclusions
While the number of patients in this study was small, the results suggest that the combination is safe and well tolerated. Disease activity was substantially reduced following the addition of MITX to IFN-ß-1b.

Twenty-five Multiple Sclerosis patients, taking part in a rehabilitation program, were randomly assigned to treatment with Pulsed Magnetic Field Therapy (PMFT) or to sham therapy in order to study the additional effect of PMFT as part of a multimodal Neurological rehabilitation program on Fatigue.

Patients demographic and disease specific characteristics were recorded. Level of Fatigue was measured by Fatigue Severity Scale (FSS) at entrance and discharge and with a Visual Analog Scale (VAS) immediate before and after a single treatment session.

The 'Magnetic Cell Regeneration' system by Santerra was used for PMFT. A single treatment lasted 16 minutes twice daily over 3-4 weeks and consisted of relaxed lying on a PMF mattress. Sham intervention was conducted in an identical manner with the PMF-device off.

Patients and statistics were blinded. Level of Fatigue measured by FSS was high at entrance in both treatment group (TG) and control group (CG) (5.6 versus 5.5).

Over time of rehabilitation Fatigue was reduced by 18% in TG and 7% in CG which was statistically not significant. There was a statistically significant immediate effect of the single treatment session which 18% reduction of Fatigue measured by VAS in TG versus 11% in CG.

Because of a high 'placebo effect' of simple bed rest, a only small and short lasting additional effect of PMFT and high costs of a PMF-device, we cannot recommend PMFT as an additional feature of a multimodal Neurological rehabilitation program in order to reduce Fatigue level of MS-patients.

Background
Awareness of the factors influencing discontinuation of ImmunoModulatory Drugs (IMD) treatment in Multiple Sclerosis (MS).

Can help to find approaches to patient management with the aim of establishing more specific indications and also attaining more optimal patient selection in future clinical trials.

Objective
To identify the causes that influence adhesion to IMD therapy within the clinical practice in a large cohort of patients with MS.

Patients And Methods
We have studied all MS patients who have initiated IMD in our hospital.

All patients took part in training sessions where treatment expectations and side effects were explained and they received training in the administration technique. Reasons for stopping therapy were recorded during follow-up.

Results
We studied 632 MS patients (mean follow-up was 47.1 (28.7) months). At the time of analysis, 107/632 patients (17%) were no longer receiving IMD.

Almost half of the patients who stopped IMD (52/107) did so within the first two years on therapy.

Fifty-six patients stopped IMD because of lack of efficacy. Only 27 patients (4.3%) discontinued treatment for reasons other than inefficacy or side effects.

The proportion of patients with Secondary/Progressive MS that stopped IMD therapy was 30%, while only 13.5% of the patients with Relapsing/Remitting MS stopped therapy (P < 0.0001).

Expanded Disability Status Scale (EDSS) score at entry was the main factor that predicted interruption of therapy.

Conclusions
The proportion of patients interrupting IMD in our center is low, possibly due to individualized care.

Higher EDSS, mainly in the first two years of treatment, is the main factor related with interruption. Close follow-up of these patients would be useful in avoiding early discontinuation of therapy.

Monocyte migration through the disrupted Cerebral Endothelial Cell (EC) junctions plays an essential role in formation of Multiple Sclerosis (MS) DeMyelinating lesions.

During pathogenesis of MS, activated ECs release Endothelial MicroParticles (EMP), which possibly facilitate TransEndothelial migration (TEMIG) of Monocytes.

To assess functional roles of EMP in MS, specifically, their:
• Interaction with Monocytes
• Effect on Monocyte TEMIG in an in vitro model of
  • Brain MicroVascular Endothelial Cells (BMVEC)
• Phenotypic profiles of EMP elicited by MS Plasma
• The effects of IFN-ß-1b on release of EMP and on
  • TEMIG of Monocytes (Mono) and Monocytes:EMP complexes (Mono:EMP) through the BMVEC

The effect of IFN-ß-1b on the release of EMP and the TEMIG of Mono and Mono:EMP was assessed by preincubating BMVEC cultures of IFN-ß 1b prior to addition of plasma.

Three EMP phenotypes, CD54, CD62E and CD31 were assayed. Plasma specimens from 20 patients with Relapsing/Remitting MS (11 in exacerbation, MS-E, and 9 in remission, ME-R) and 10 healthy controls were studied.

Incubation of BMVEC with MS-E plasma yielded elevated levels of EMPCD54, EMP62E and EMPCD31 relative to MS-R and control Plasmas.

MS-E but not MS-R or control Plasma also augmented TEMIG of Monocytes, respectively.

Mono:EMP complexes further augmented TEMIG relative to Mono alone, but only in the presence of MS-E Plasma; there was no significant effect with MS-R or control Plasmas.

The presence of IFN-ß-1b inhibited TEMIG of Mono and Mono:EMP by 20% and 30%, respectively.

MS-E but not MS-R plasma elicited release of activation-derived EMP and enhanced TEMIG of Mono and Mono:EMP.

IFN-ß-1b inhibited TEMIG and release of EMP, suggesting a role of EMP and a novel therapeutic mechanism for IFN-ß-1b in MS.

We investigated ElectroPhysiological correlates of Fatigue in patients with Multiple Sclerosis (MS).

TransCranial Magnetic Stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with Fatigue (MS-F), MS patients without Fatigue (MS-NF) and healthy control subjects.

All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the Motor Task, MS-F patients had less inhibition in the Primary Motor Cortex compared to both other groups.

Postexercise, IntraCortical Inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the Motor Threshold was correlated with the Fatigue severity.

We conclude that MS patients with Fatigue have an impairment of Inhibitory Circuits in their Primary Motor Cortex. The results also indicate that Fatigue severity is associated with an exercise-induced reduction of membrane excitability.

Introduction
This study used reliable and validated instruments to compare Pain severity in Multiple Sclerosis (MS) to that in other chronic painful conditions, and to examine relationships between chronic Pain in MS and health-related quality of life (HRQOL).

Methods
Ninety-nine MS patients completed a self-administered survey comprised of the Medical Outcomes 36-Item Short-Form Health Survey, the Short-Form McGill Pain Questionnaire, and the Hospital Anxiety and Depression Scale.

Results
Pain severity was not different between MS patients with pain and Rheumatoid Arthritis (P = 0.77) or OsteoArthritis (P = 0.98) patients.

Chronic Pain in MS was less often Neurogenic than Non-Neurogenic, although severity of Neurogenic Pain was greater than that of Non-Neurogenic Pain (P = 0.048).

Chronic pain in MS was found to have no significant relationship to age, disease duration or disease course.

Instead, we found that pain was correlated with aspects of HRQOL, particularly mental health (r = 0.44, P < 0.0001) versus physical functioning (r = 0.19, P > 0.05).

Chronic pain was significantly related to Anxiety and Depression for females but not for males with MS.

Conclusions
Chronic pain in MS is as severe as pain in Arthritic conditions and is associated with reduced HRQOL. Thus, pain can be a significant symptom for MS patients and the need for treatment may be underestimated.

Pedometers are inexpensive and user-friendly devices that might be practical for measuring physical activity among individuals with Multiple Sclerosis (MS).

This study involved an evaluation of the accuracy of two pedometers against actual steps taken under controlled laboratory conditions (five minute bouts of walking at five different treadmill speeds [41, 54, 67, 80, and 94 m x min(-1)]) among 23 individuals with MS who were ambulatory without an aide.

Both pedometers exhibited good accuracy with the 67, 80, and 94 m x min(-1) speeds, but poor accuracy with the 41 and 54 m x min(-1) speeds.

Those results support the quantification of physical activity using pedometers among those with MS who are ambulatory without an aide.

Malignant forms of Multiple Sclerosis (MS) represent a limited group of very aggressive DeMyelinating Diseases, which rapidly progress to severe disability leading often to life-threatening conditions.

On these clinical entities, currently available therapies for MS are not very effective.

Recently, it has been demonstrated that intense ImmunoSuppression followed by Autologous Stem Cell Transplantation (ASCT) can affect the clinical course of individuals with severe MS.

And completely abrogate the inflammatory activity detected by Magnetic Resonance Imaging (MRI).

We report on the treatment with intense Immune ablation followed by ASCT of three patients with malignant MS whose clinical course indicated a dramatically poor prognosis.

This procedure succeeded in halting the rapidly worsening course of disease.

The effect was long lasting, as demonstrated by a sustained efficacy over a two-year period in two subjects and 12 months in the third case.

In addition, a striking effect on inflammation-related MRI findings was obtained.

These results support a role for intense ImmunoSuppression followed by ASCT as treatment in rapidly evolving malignant MS cases unresponsive to conventional therapies.

We conducted an evaluation of changes in Cognition in Progressive Multiple Sclerosis (MS) patients receiving monthly intravenously pulse of Cyclophosphamide (700 mg/m2) with MethylPrednisolone (1g).

Twenty-eight consecutive Progressive MS patients (10 Primary/Progressive, 18 Secondary/Progressive MS) were evaluated before and after six and 12 months of treatment.

The WAIS-R score, Memory and Executive Functions were evaluated.

Under treatment we found a significant improvement in global Cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months.

However, mechanisms of action of the positive effect of these Anti-Inflammatory and ImmunoSuppressive treatments on Cognition remain unclear.

The revision of MEDLINE from 1966 to 2003 did not report any association between Multiple Sclerosis (MS) and Melkersson-Rosenthal Syndrome (MRS).

This is a case report of a 51-year-old woman, with history of four recurrent Bell's Palsies.

In 1999 she developed a right facial paralysis due to a SupraNuclear Pyramidal lesion with Right MonoParesis.

The family history showed five relatives with recurrent Bell's Paralysis and plicata tongue.

Physical examination: Right Bell's paralysis, Left Supranuclear facial paralysis, furrowed tongue, Right HemiParesis with pallor of the Optic Disks.

Brain Magnetic Resonance Imaging (MRI) demonstrated the typical lesions of MS and CSF OligoClonal Bands. This is the first observation of a patient with hereditary MRS and MS.

The link between both diseases is discussed.