MS Abstracts 05b-2g1

Correlation studies between various conventional and non-conventional MRI parameters and Cognitive Impairment in the early stages of Multiple Sclerosis (MS) are lacking.

Although it is known that a number of patients with early MS have mild Cognitive Impairment.

Our aim was to explore whether this Cognitive Impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic Brain damage or both.

We studied 63 patients with clinically definite Relapsing/Remitting (R/R) MS, duration of disease 1-10 years and Expanded Disability Status Scale scores < or = 5.0.

Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5.

NeuroPsychological performance, Psychological function, Neurological impairment and Disability were assessed. The patients also underwent MRI, including Magnetization-Transfer (MT) studies.

We quantified the lesion load on T₂- and T₁-weighted images, the Magnetization Transfer Ratio (MTR) of Normal-Appearing Brain Tissue (NABT) and the Brain Parenchymal Fraction (BPF).

No significant difference was found between lesion loads in patients with and without Cognitive Impairment.

In 15 patients (23.8%) with overall Cognitive Impairment, median BPF and average NABT MTR were significantly lower than those in patients without Cognitive Impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively).

Multiple regression analysis models demonstrated that the only variables independently correlated with Cognitive Impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012).

Our findings support the hypothesis that, Cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse Brain damage.

The loss of Brain Parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease.

Pericytes are PeriVascular Cells with multifunctional activities which are now being elucidated.

The functional interaction of Pericytes with Endothelial Cells (EC) is now being established, using current molecular and CytoChemical techniques.

The detailed morphology of the Pericyte has been well described. Pericytes extend long CytoPlasmic Processes over the surface of the EC, the two cells making interdigitating contacts.

At points of contact, communicating gap junctions, tight junctions and adhesion plaques are present. Pericytes appear to show both structural and functional heterogeneity.

The coverage of ECs by Pericytes varies considerably between different MicroVessel types and the location of Pericytes on the MicroVessel is not random but appears to be functionally determined.

Interaction between Pericytes and EC is important for the maturation, remodelling and maintenance of the Vascular System via the secretion of Growth Factors or modulation of the ExtraCellular Matrix.

There is also evidence that Pericytes are involved in the transport across the Blood-Brain Barrier and the regulation of Vascular permeability.

The long-standing view that Pericytes are the MicroVessel equivalent of larger vessel smooth muscle cells and are contractile is being re-assessed using current methods.

An important role for Pericytes in pathology, and NeuroPathology in particular, has been indicated in Hypertension, Diabetic Retinopathy, Alzheimer's Disease, Multiple Sclerosis and CNS Tumor formation.

Copyright 2001 S. Karger AG, Basel

Purpose
Botulinum Toxin injection into the External Urinary Sphincter in Spinal Cord injured men with Detrusor-Sphincter DysSynergia has been reported.

We expand the clinical use of Botulinum Toxin for a variety of Bladder Outlet obstructions and to decrease outlet resistance in patients with Acontractile Detrusor but who wish to void by the Valsalva maneuver.

Materials And Methods
Prospective treatment was performed for voiding dysfunction in 8 men and 13 women 34 to 74 years old.

The reasons for voiding dysfunction included Neurogenic Detrusor-Sphincter DysSynergia in 12 cases, pelvic floor Spasticity in 8 and Acontractile Detrusor in 1 patient with Multiple Sclerosis who wished to void by the Valsalva maneuver.

Using a rigid cystoscope and a Collagen injection needle, a total of 80 to 100 units of Botulinum A toxin (Botox*) were injected into the External Sphincter at the 3, 6, 9 and 12 o'clock positions.

Results
Preoperatively 19 of 21 patients were on indwelling or intermittent catheterization. After Botulinum A injection all but 1 patient were able to void without catheterization.

No acute complications, such as general Paralysis or Respiratory Depression, occurred and none of the patients had dribbling or stress Urinary Incontinence.

Postoperative post-void residual decreased by 71% and voiding pressures decreased on average 38%. Of the 21 patients 14 (67%) reported significant subjective improvement in voiding.

Followup ranges from 3 to 16 months, with a maximum of 3 Botulinum A injections in some patients.

Conclusions
Urethral Sphincter Botulinum injection should be considered for complex voiding dysfunction. Encouraging improvement without complications were seen in most of our patients.

We have expanded the use of Botulinum Toxin to treat Pelvic Floor Spasticity and also women.

The prevalence of Bowel Dysfunction in Multiple Sclerosis (MS) patients is higher than in the general population. Up to 70% of patients complain of constipation or faecal incontinence, which may also coexist.

This overlap can relate to Neurological Disease affecting both the Bowel and the Pelvic floor muscles, or to treatments given. >Bowel dysfunction is a source of considerable ongoing PsychoSocial disability in many patients with MS.

Symptoms related to the Bladder and the Bowel are rated by patients as the third most important, limiting their ability to work, after Spasticity and Incoordination. Bowel management in patients with MS is currently empirical.

Although general recommendations include maintaining a high fiber diet, high fluid intake, regular Bowel routine, and the use of enemas or laxatives, the evidence to support the efficacy of these recommendations is scant.

This review will examine the current state of knowledge regarding the PathoPhysiological mechanisms underlying Bowel Dysfunction in MS.

Outline the importance of proper clinical assessment of constipation and Faecal Incontinence during the diagnostic work-up, and propose various management possibilities.

In the absence of clinical trial data on Bowel management in MS, these should be considered as a consensus on clinical practice from a team specialized in Bowel Dysfunction.

Increased risk of Multiple Sclerosis has been reported among individuals with a history of Measles and other common childhood diseases during adolescence, infectious Mononucleosis, or exposure to the Canine Distemper Virus.

We investigated these associations in a case-control study nested within the Nurses' Health Study (121,700 women traced since 1976) and the Nurses' Health Study II (116,671 women traced since 1989).

Age at diagnosis of common Viral diseases and birth order were obtained through a questionnaire. Our results include 301 cases with Multiple Sclerosis and their (up to six) matched controls.

Except for infectious Mononucleosis, which was a moderate risk factor (odds ratio = 2.1, 95% confidence interval = 1.5-2.9).

We found little association between history of common Viral diseases or exposure to Canine Distemper Virus and risk of Multiple Sclerosis.

We did find a relation between Mumps after 15 years of age (odds ratio = 2.3, 95% confidence interval = 1.2-4.3) or Measles after age 15 years of age (odds ratio = 2.8, 95% confidence interval = 0.8-9.1) and Multiple Sclerosis.

Birth order was not materially related to Multiple Sclerosis.

Our findings support the hypothesis that individuals who suffered from infectious Mononucleosis, a marker of late infection with the Epstein-Barr Virus, have an increased risk of Multiple Sclerosis.

Late infection with other common Viruses may also be associated with increased risk.

A Visual complaint such as blurred or 'washed-out vision' can be one of the early signs of Multiple Sclerosis (MS).

Although Visual deficits are commonly attributed to Optic Nerve DeMyelination even with preserved Visual Acuity.

The results of a considerable number of Visual studies are inconsistent with this interpretation: [Camisa, Mylin, & Bodis-Wollner, Annals of Neurology 10 (1981) 532-539; Regan & Neima, British Journal of Ophthalmology 68 (1984) 310-315].

However, a Retinal Axonal (Nerve Fiber Layer) defect can be detected in some Eyes, this is not the rule.

Routine Visual Field (VF) tests, with a low sampling rate may also be non-informative in MS and Optic Neuritis, possibly because the VF abnormalities may be small and spotty or they can be found between tested points.

The present study combined the advantages of VF and Contrast Sensitivity (CS) testing by applying Contrast Perimetry (CP), to the central 16 degrees of the VF.

Four ParaCentral VF quadrants were tested in clinically affected and unaffected eyes of 31 MS patients and 26 controls.

The stimuli were vertical Gaussian apertured sinusoidal gratings (Gabors) of 1 cpd. CS was obtained as a function of the diameter of the Gabor ranging from 1 to 7.4 degrees.

The CP data of controls and Definite and Probable MS groups were significantly different for each pattern size, but the largest difference was found at diameters 2.5-3.7 degrees.

Our study adds to previous evidence showing that Optic Nerve pathology does not explain 'subclinical' and manifest Visual dysfunction in MS. Given previous studies revealing orientation dependent MonOcular Visual deficits and our study results.

Parsimony suggests that MS affects a network relying on Myelinated Lateral Axonal branches of the Visual Cortex, binding MonOcular columns of Neurons with-like specificity.

Introduction
The effect of combined treatment (MethylPrednisolone and Cyclophosphamide) of Multiple Sclerosis relapse within one year was investigated in an open clinical trial study of 70 patients.

The sample comprised subjects shown to have clinically proven Multiple Sclerosis according to the criteria of C Poser and degree of Neurological deficit according to EDSS rating from 2.5 to 6.0 points.

Material And Methods
MethylPrednisolone (200 mg, i.v., every other day, 10 doses, total course dose 2 g) was administered to 35 patients (mean age 31.34 +/- 1.53 years).

MethylPrednisolone using the same schedule and Cyclophosphamide (200 mg, i.v.) given in the MethylPrednisolone-free day, 10 doses plus 200 mg i.v. once a month in the first three consecutive months (total course dose 2.6 g) were applied in another 35 patients (mean age 33.22 +/- 1.32 years).

Results And Discussion
The changes of EDSS ratings at the end of months 1 and 12, of the CD8⁺ T-Lymphocytes subpopulations and B-Lymphocytes from peripheral blood - prior to treatment and between the 5th and 9th week of treatment were compared.

The Neurological deficit degree according to EDSS dropped significantly (P < 0.01; P < 0.001) after one month of treatment in both groups.

At the end of month 12 this indicator reached its baseline value in the group treated only with MethylPrednisolone while remaining significantly lower in the combined therapy group (P < 0.01).

After MethylPrednisolone and Cyclophosphamide application the Suppressor/Inducer CD8⁺ T-Cells increased significantly in percentage (P < 0.05).

While the values of B-Lymphocytes decrease significantly (P < 0.05), in contrast to the results from the MethylPrednisolone-only treatment.

Conclusions
The results clearly indicate the greater efficaciousness of treatment by combining two ImmunoSuppressive drugs.

Introduction
Acute Disseminated EncephaloMyelitis (ADEM) is a postinfectious Encephalitis that is usually preceded by an infectious disease or vaccination.

The clinical presentation has a wide spectrum and complementary exams are none specific, except Magnetic Resonance Imaging (MRI) findings showing multifocal White Matter lesions similar to those seen in Multiple Sclerosis.

Patients And Methods
We report 10 children with the diagnosis of ADEM. We describe the clinical course and response to treatment.

Results
The prodroms were fever in all cases except one. The most common Neurological symptoms were Consciousness Impairment, Headache and Seizures.

The CerebroSpinal Fluid examination was abnormal in 9 patients with positive serologic test to EnteroVirus in one of them. MRI showed HyperIntense multifocal SubCortical White Matter lesions on T₂-weighted images.

Treatment with Steroids was given to 5 patients, Steroids and ImmunoGlobulins to one patient and symptomatic treatment to the rest. From the last group one patient relapsed and then received CorticoSteroid treatment.

The follow up revealed a complete recovery in 6/7 patients that received steroids. Three patients have sequelae and of these, 2 received only symptomatic treatment.

Conclusions
The diagnosis of ADEM is based on clinical and radiologic features, once other entities have been excluded.

At the moment of suspicious of ADEM a Brain-Spinal Chord MRI should be done, seeing that TAC brings not much information at the beginning.

The treatment with Steroids seems to be the most effective and the prognosis good, specially in cases that respond rapidly to it.

Objective
To examine the predictive validity of the Self-Reported Functional Measure (SRFM).

A new measure derived from the FIM instrument, for health care utilization in Multiple Sclerosis (MS) and Spinal Cord Injury (SCI).

Design & Setting
Prospective cohort study using a mailed survey in 1995 and administrative records from 1996 and 1997. Veterans Health Administration hospitals and outpatient clinics.

Patients & Main Outcome Measures
A total of 6361 veterans with SCI and 1789 veterans with MS. SRFM score was compared with subsequent outpatient visits, hospitalizations, hospital lengths of stay (LOSs), and residence peri-hospitalization.

Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for these variables.

Results
A total of 3836 subjects (47.6%) were hospitalized during 1996-1997, and all but 874 (10.7%) had 1 or more outpatient visits. SRFM score predicted inpatient, but not outpatient health care utilization.

Persons in the lowest SRFM quartile were over 90% (OR = 1.91, 95% CI = 1.71-2.13) more likely to be hospitalized compared with those in the highest SRFM quartile.

Also, they were over 2 times (OR = 2.18, 95% CI = 1.85-2.57) more likely to have a LOS greater than 7 days, were over 2 times (OR = 2.41, 95% CI = 1.62-3.58) more likely to die in hospital.

And were nearly 3 times (OR = 2.86, 95% CI = 2.00-4.08) more likely to be discharged to an institution.

Conclusions
SRFM had excellent predictive validity for hospitalization, LOS, and discharge destination among patients with MS or SCI.

Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation