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Multiple Sclerosis - Abstracts 7b-2g

  1. Gut focused behavioral treatment (biofeedback) for Constipation and Faecal Incontinence in Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2000 Aug;69(2):240-243

  2. Multiple Sclerosis-From Probable to Definite Diagnosis: A 7-Year Prospective Study
    Arch Neurol 2000 Jul;57(7):974-979

  3. Hyperactive tendon reflexes in spastic Multiple Sclerosis: measures and mechanisms of action
    Arch Phys Med Rehabil 2000 Jul;81(7):901-9

  4. Low-Dose Gabapentin Combined with either Lamotrigine or Carbamazepine Can Be Useful Therapies for Trigeminal Neuralgia in Multiple Sclerosis
    Eur Neurol 2000 Jul;44(1):45-48

  5. Effect of precooling on physical performance in Multiple Sclerosis
    Mult Scler 2000 Jun;6(3):176-80

  6. Activated T-Cell Changes in blood correlate with disease activity in Multiple Sclerosis
    Arch Neurol 2000 Aug;57(8):1183-1189

  7. Acute Aphasia in Multiple Sclerosis
    Arch Neurol 2000 Aug;57(8):1207-1209

  8. Monocytes in Multiple Sclerosis: phenotype and Cytokine profile
    J NeuroImmunol 2001 Jan 1;112(1-2):197-205

  9. Extended observations on the association of HHV-6 and Multiple Sclerosis
    J NeuroVirol 2000 May;6 Suppl 2:S85-7


Gut Focused Behavioral Treatment (Biofeedback) For Constipation And Faecal Incontinence In Multiple Sclerosis

Wiesel PH, Norton C, Roy AJ, Storrie JB, Bowers J, Kamm MA
J Neurol NeuroSurg Psychiatry 2000 Aug;69(2):240-243
St Mark's Hospital, Dept of Gastroenterology and Physiology, Northwick Park, Watford Road, Harrow HA1 3UJ, London, UK
PMID# 10896701

To determine whether gut focused behavioral treatment (Biofeedback) is a useful therapy in Multiple Sclerosis patients referred for Constipation, Incontinence, or a combination of these symptoms.

Most patients with Multiple Sclerosis complain of Constipation, Faecal Incontinence, or a combination of the two.

Patients rate these bowel symptoms as having a major impact on their life. Until now the management of these problems has been empirical, with a lack of evaluated therapeutic regimes.

Thirteen patients (eight women, median age 38 years, median duration of Multiple Sclerosis 10 years) complaining of Constipation, with or without Faecal Incontinence underwent a median of four sessions of behavioral treatment.

Anorectal Physiological Tests were performed before therapy. Impairment and disability were rated with the Kurtzke score and the Cambridge Multiple Sclerosis basic score (CAMBS). Patients were contacted a median of 14 months after completion of treatment.

A beneficial effect was attributed to biofeedback in five patients.

Mild to moderate disability, quiescent and Non-Relapsing Disease, and absence of progression of Multiple Sclerosis over the year before Biofeedback were predictive of symptom improvement. No physiological test predicted the response to therapy.

Biofeedback retraining is an effective treatment in some patients with Multiple Sclerosis complaining of Constipation or Faecal Incontinence.

A response is more likely in patients with limited disability and a Non-Progressive Disease course.


Multiple Sclerosis-From Probable To Definite Diagnosis

A 7-Year Prospective Study
Achiron A, Barak Y
Arch Neurol 2000 Jul;57(7):974-979
Multiple Sclerosis Center, Sheba Medical Center, Tel Hashomer 52621, Israel
PMID# 10891979

To investigate the rate of progression from Probable to Clinically Definite Multiple Sclerosis (MS) and to define patients who had rapidly (within 1 year) progressed to a definite diagnosis.

Design & Patients
A 7-year prospective study. A group of 163 patients experiencing their first episode of Neurologic symptoms suggestive of MS.

All patients had Brain Magnetic Resonance Imaging that demonstrated at least 3 DeMyelinating lesions at onset.

Within the follow-up period (mean, 42 months; range, 13-84 months), 136 patients (83.4%) had an additional relapse and were thus defined as having Clinically Definite MS.

Whereas, 27 patients (16.6%) were defined as having Clinically Probable MS.

Most of the 136 patients with Clinically Definite MS (57.6%, 94 patients) experienced the additional relapse within 1 year.

Demographic and clinical parameters at presentation were analyzed to identify variables predictive of rapid progression (within 1 year) to Clinical Definite MS.

Motor involvement at Onset was the only clinical parameter associated with rapid progression to a definite diagnosis.

Survival curves demonstrated that PolySymptomatic involvement and higher Extended Disability Status Scale score at presentation correlated with rapid progression to definite diagnosis.

Most patients with a diagnosis of Probable MS and positive Brain Magnetic Resonance Imaging will progress rapidly to Clinically Definite MS.

Arch Neurol 2000;57:974-979


Hyperactive Tendon Reflexes In Spastic Multiple Sclerosis: Measures And Mechanisms Of Action

Zhang LQ, Wang G, Nishida T, Xu D, Sliwa JA, Rymer WZ
Arch Phys Med Rehabil 2000 Jul;81(7):901-9
Rehabilitation Institute of Chicago, and Northwestern University, Dept of Physical Medicine and Rehabilitation, Chicago, IL, USA
PMID# 10896002; UI# 20352898

To develop new measures of tendon reflexes and evaluate hyperactive reflexes in patients with Spastic Multiple Sclerosis (MS).

With the subject relaxed, a hand-held instrumented hammer was used to tap the patellar tendon and record the tapping force.

While knee extension torque and quadriceps EMG were recorded isometrically as measures of the reflex response.

Setting & Subjects
Research laboratory in a rehabilitation hospital. Ten Spastic MS and 14 healthy subjects.

Main Outcome Measures
Tendon tapping force (designated as system input), reflex torque (as output), their dynamic relationship (characterized as system parameters tendon reflex gain, contraction rate, and reflex loop delay), Ashworth scale, and tendon reflex scale.

The system parameters provide more repeatable measures than do input or output parameters alone because they quantify the input and output simultaneously and dynamically.

Compared with control subjects, MS patients had a significantly lower threshold in tapping force (p = .026), yet their evoked reflex torque was significantly higher (p = .033).

Despite significant quadriceps weakness (p < .0001), MS patients had a significantly higher reflex gain (p = .0002) and contraction rate (p = .0002), and shorter reflex loop delay (p = .0046), indicating hyperexcitability of MotoNeurons and peripheral receptors.

And indicating that relatively more of the muscle was activated reflexively, with greater recruitment of larger fast-twitch Fibers.

Both the reflex gain and rate measures correlated more closely with the Ashworth scale and tendon reflex scale than did the output measures, indicating their potential clinical value.

With appropriate simplification, the method may be used in clinical practice to quantify more precisely the tendon jerk than is currently feasible with standard clinical tests.


Low-Dose Gabapentin Combined With Either Lamotrigine Or Carbamazepine Can Be Useful Therapies For Trigeminal Neuralgia In Multiple Sclerosis

Solaro C, Messmer Uccelli M, Uccelli A, Leandri M, Mancardi GL
Eur Neurol 2000 Jul;44(1):45-48
Univ of Genoa, Dept of Neurological Sciences and Rehabilitation, Genoa, Italy
PMID# 10894995

Paroxysmal symptoms occur frequently in Multiple Sclerosis (MS). Usually they are treated with Carbamazepine (CBZ) and Phenytoin, although these medications are often interrupted due to adverse effects.

We report 11 MS patients with Trigeminal Neuralgia (TN):

  1. Group 1: 6 intolerant to a therapeutic dosage of CBZ, showing serious adverse effects and subsequently treated with a combination of low-dose CBZ and Gabapentin (GBP)

  2. Group 2: 5 treated with Lamotrigine (LMT), showing adverse effects and subsequently treated with GBP

Subjective pain level and Impairment in performing daily activities were rated utilizing a 3-point scale at time 0 and at optimal dosage time (T1).

GBP was initiated at 300 mg daily and titrated, until pain control was achieved without new adverse effects, to a maximum dose of 1,200 mg daily.

CBZ or LMT were reduced to a level which no longer produced adverse effects, although resulting in a lack of efficacy in relieving pain.

Pain control was obtained in all patients but 1, with no side effects. The Plasma level analysis, performed in 5 patients, resulted in normal values.

The mean dosages at T1 were: group 1 CBZ 400 mg and GBP 850 mg daily; group 2 LMT 150 mg and GBP 780 mg daily.

Combining drugs with complementary modes of action may provide a rational pharmacological approach to the management of TN in MS.

Copyright 2000 S. Karger AG, Basel


Effect Of Precooling On Physical Performance In Multiple Sclerosis

White AT, Wilson TE, Davis SL, Petajan JH
Mult Scler 2000 Jun;6(3):176-80
Univ of Utah, Dept of Exercise and Sport Science, Salt Lake City, Utah UT 84112, USA
PMID# 10871829; UI# 20332496

Many individuals with MS experience Heat Sensitivity that may be associated with transient increases in the frequency of clinical signs and symptoms.

Although physical activity may be beneficial for those with MS, induced thermal loads may preclude participation in exercise and other daily activities.

This project was designed to evaluate the effects of precooling on physical function. Six thermosensitive MS patients were studied.

Participants performed a graded exercise test to determine maximal Oxygen uptake (VO2max) on a combined arm-leg ergometer.

Thermal load was induced by 30 min of exercise under noncooled and precooled conditions at a workrate corresponding to 60% VO2max.

Precooling consisted of 30 min lower body immersion in 16 - 17 degrees C water. Fatigue and 25-ft walk performance were assessed before, immediately after, and 30 min following exercise.

No treatment differences in VO2 were observed.

Rectal temperature, heart rate, and rating of perceived exertion (RPE) were significantly lower during the precooled exercise trial compared to the noncooled trial.

Immediately following exercise, 25-ft walk performance and Fatigue scores showed significantly greater deterioration in the noncooled condition.

Precooling was effective in preventing gains in core temperature with physical work and may allow Heat-Sensitive individuals with MS to exercise with greater physical comfort.

Multiple Sclerosis (2000) 6, 176 - 180


Activated T-Cell Changes In Blood Correlate With Disease Activity In Multiple Sclerosis

Khoury SJ, Guttmann CR, Orav EJ, Kikinis R, Jolesz FA, Weiner HL
Arch Neurol 2000 Aug;57(8):1183-1189
Center for Neurologic Diseases, 77 Ave Louis Pasteur, Boston, MA 02115
PMID# 10927799

To determine whether changes in activation markers on peripheral blood T-Cells correlate with disease activity in patients with Multiple Sclerosis.

In a prospective longitudinal study during 1 year, we analyzed the change in percentage of activated T-Lymphocytes in the peripheral blood of 40 patients with Multiple Sclerosis in relation to clinical findings and changes on Brain Magnetic Resonance Imaging (MRI) scans.

The patients underwent repeated imaging of the Brain (mean number of MRIs for each patient, 22) at the time blood samples were obtained as well as at monthly Neurological Examinations, and at the time of scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and Ambulation Index Scale.

A change in the percentage of cells expressing the activation markers InterLeukin 2 receptor (CD25+), Class II Major Histocompatibility Complex (MHC) (I3) or surface Dipeptidyl Peptidase (CD26+) correlated significantly with a change in lesion volume or a change in number of Gadolinium-enhancing lesions as detected on MRI.

Changes in CD25+ cells and in CD4+ cells expressing class II MHC also correlated with changes in disability as measured by EDSS in patients with Relapsing/Remitting Disease, and changes in CD4+, CD25+ cells correlated with the occurrence of attacks in patients with Relapsing/Remitting Disease.

These correlations are dependent on measurement of changes between time points sampled at 1- or 2-week intervals.

There is a linkage between peripheral T-Lymphocyte activation as measured by cell surface markers and disease activity in patients with Multiple Sclerosis.

Arch Neurol 2000;57:1183-1189


Acute Aphasia In Multiple Sclerosis

Devere TR, Trotter JL, Cross AH
Arch Neurol 2000 Aug;57(8):1207-1209
Barnes Jewish Hospital, Campus Box 8111, 660 S Euclid Ave, St Louis, MO 63110
PMID# 10927803

Acute Aphasia is rare in Multiple Sclerosis. We describe 3 patients with Multiple Sclerosis who had acute exacerbations presenting as Aphasias.

One patient had a mixed TransCortical Aphasia, 1 had a TransCortical motor Aphasia, and 1 had a Broca Aphasia. Magnetic Resonance Imaging scans of the Brain with contrast enhancement revealed new White Matter lesions in the Left Hemisphere in all 3 patients.

Two of the 3 patients had a good response to treatment with MethylPrednisolone Sodium Succinate.

Arch Neurol 2000;57:1207-1209


Monocytes In Multiple Sclerosis: Phenotype And Cytokine Profile

Kouwenhoven M, Teleshova N, Ozenci V, Press R, Link H
J NeuroImmunol 2001 Jan 1;112(1-2):197-205
Karolinska Institutet, Huddinge Univ Hospital, NeuroImmunology Unit, Division of Neurology, Stockholm, Sweden
PMID# 11108949

Multiple Sclerosis (MS) is an inflammatory DeMyelinating disease characterized by Immune abnormalities in the Central Nervous System (CNS) as well as systemically.

Activated, blood-borne Monocytes are abundant in MS lesions, the properties of circulating Monocytes are incompletely known.

To delineate phenotype and levels of Cytokine secreting Monocytes in MS patients' blood, ELISPOT assays were used for detection and enumeration of Monocytes secreting the Cytokines IL-6, IL-12, TNF-alpha and IL-10.

In parallel, the expression by Monocytes of co-stimulatory molecules (CD40, CD80, CD86), Major Histocompatibility Complex molecules (HLA-ABC, HLA-DR) and Fcgammareceptors (CD16, CD64) was examined by flow cytometry.

Levels of blood Monocytes secreting IL-6 and IL-12 were higher in patients with untreated MS and Other Neurological Diseases (OND) compared to healthy controls, while levels of Monocytes secreting TNF-alpha and IL-10 did not differ between groups.

MS patients' blood Monocytes also displayed elevated mean fluorescence intensity for the co-stimulatory molecule CD86, and MS patients with longer disease duration (>10 years) and higher disease severity (EDSS >3) had higher percentages of CD80 expressing Monocytes compared to patients with short duration or lower severity.

In conclusion, Monocyte aberrations occur in MS and may change over the disease course.


Extended Observations On The Association Of HHV-6 And Multiple Sclerosis

Berti R, Soldan SS, Akhyani N, McFarland HF, Jacobson S
J NeuroVirol 2000 May;6 Suppl 2:S85-7
National Institutes of Health, NeuroImmunology Branch, Viral Immunology Section, Bethesda, Maryland, MD 20892, USA
PMID# 10871792; UI# 20332469

Throughout the years, a long list of Viruses has been associated with Multiple Sclerosis (MS), however no virus to date has been definitively identified as the etiologic agent of this disease.

Recently, Human HerpesVirus 6 (HHV-6), a newly described HerpesVirus, has been suggested to play a role in MS based on: ImmunoHistoChemical demonstration of HHV-6 in MS plaques.

Increased AntiBodies response to HHV-6 in Sera and CSF of MS patients, and the demonstration of HHV-6 DNA in the Serum of MS patients but not in normal individuals. To extend these observations we have focused our research in multiple directions.

We have increased the number of MS patients tested for HHV-6 Serum DNA providing confirmation of our previous study. Additionally we have investigated a possible correlation between HHV-6 Viremia and clinical activity.

Finally to provide insight into the PathoGenesis of this disease, we have begun to characterize the Cellular Immune Response of MS patients to HHV-6. Collectively these studies will help to define the role that HHV-6 may play in the PathoGenesis of MS.

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