The aim of this work was, first, to clarify the nature of the relationship between the Sensory deficit in the DeMyelinated Visual Pathway and morphological changes revealed by MRI.

And, secondly, to test whether there was a preferential effect of DeMyelination for either the MagnoCellular or ParvoCellular Pathway in established Multiple Sclerosis.

Twenty-four patients with Secondary/Progressive Multiple Sclerosis were studied PsychoPhysically and by MRI of the Optic Nerve and Brain. MRI was performed with a Phillips (0.5T) scanner.

Visual Pathway MRI lesion load was evaluated independently using the total Optic Nerve lesion length and lesion area seen on STIR (Short Inversion Time Inversion Recovery) images of the Optic Nerve.

And, the total Post-Chiasmal lesion area on T₁-, T(2)- and Proton-Density-weighted images of the Brain.

PsychoPhysical tests determined 75%-seeing thresholds for horizontal gratings consisting of IsoLuminant red and green Sinusoids of the same spatial frequency.

Combined out-of-phase for preferential stimulation of the ParvoCellular System and in-phase for preferential stimulation of the MagnoCellular System.

It was found that, in this group of patients, Visual PsychoPhysical loss was significantly correlated with Lesion area seen on Proton Density MRI sequences of the Post-Chiasmal Visual Pathway.

And, that the ParvoCellular pathway was more affected than the MagnoCellular pathway, especially at lower spatial frequencies.

Local Field Potentials (LFPs) were recorded in seven unanaesthetized patients between the four adjacent contacts of a MacroElectrode stereotactically implanted for the treatment of Tremor.

The LFPs were presumed to arise predominantly from the Nucleus Ventralis Intermedius (Vim) of the Thalamus, the implantation target.

They were recorded simultaneously with the IpsiLateral EEG and ContraLateral EMG during an isometric contraction or at rest.

1. The patients had a history of either isolated Tremor (Essential Tremor, n = 2; Benign Tremulous Parkinson's Disease, n = 1) or

2. Tremor with signs of a Cerebellar Syndrome (Multiple Sclerosis, n = 3; Essential tremor and Ataxia, n = 1),

3. Although clinical Tremor was absent at the time of recording because of a temporary MicroThalamotomy effect in four patients.

In patients with Isolated Tremor, Oscillatory activity picked up by contacts in Vim (Cerebellar Thalamus) was invariably coherent with that in the SensoriMotor Cortex or contracting muscle in the 8-27 Hz range.

Such coherence was absent in two of the four subjects with Tremor associated with a Cerebellar Syndrome.

Coherence between LFPs recorded from more Caudally placed contacts and the SensoriMotor Cortex or contracting muscle was negligible in all patients.

These Caudally placed contacts demonstrated the highest Sensory Evoked Potential in response to Median Nerve stimulation.

Oscillatory activity in the Cerebellar Thalamus (Vim) lagged behind that in both Cortex and muscle. Coherent activity between the Cerebellar Thalamus (Vim) and the Cortex persisted at rest.

It is suggested that rhythmicities in the 8-27 Hz range could provide the basis for a temporal framework that is widely distributed within the Motor System.

Objective
To compare Brain metabolite levels in patients with Primary/Progressive (PP) and Relapsing/Remitting (RR) MS and controls.

Hypotheses
1. Creatine (Cr), a putative marker of Gliosis, is elevated and N-AcetylAspartate (NAA), a putative marker of Axonal density and functional integrity, is reduced in PPMS lesions and Normal-Appearing White Matter (NAWM) compared to control White Matter
   
   
2. The pattern of metabolite change in PPMS is different than in RRMS

Methods
MRI and Proton Magnetic Resonance Spectroscopic Imaging (1H MRSI) were collected from 15 PPMS patients, 13 RRMS patients, and 20 controls.

Results
Cr was increased in PPMS NAWM compared to controls (P=0.035), and compared to RRMS NAWM (P=0.038).

Cr was increased in focal MRI lesions from PPMS compared to lesions from RRMS (P=0.044) and compared to control White Matter (P=0.041).

NAA was similarly reduced in PPMS and RRMS NAWM compared to control.

NAA was similarly reduced in PPMS and RRMS lesions, compared to control White Matter.

Conclusions
Creatine is higher in PPMS than RRMS NAWM and Focal lesions.

This observation is consistent with the notion that progressive Disability in PPMS reflects increased Gliosis and Axonal Loss.

Whereas, Disability in RRMS reflects the cumulative effects of Acute Inflammatory Lesions and Axonal Loss.

Differential expression of InterLeukins may influence susceptibility to Inflammatory Diseases such as MS.

IL-1a production is increased in MS patients during acute relapse, IL-2 Receptor (IL-2R) secretion correlates with disease activity in several inflammatory disorders and is variable in MS.

Both IL-4 and IL-10 expression vary significantly with relapse/remission in MS and IL-9 is postulated to inhibit Steroid-induced Apoptosis.

To examine the influence of InterLeukin (IL) Genes on MS susceptibility and clinical course, Gene association studies using separate polymorphic microsatellite markers for IL-1, IL-2, IL-2rß, IL-4 IL-9 and IL-10 were performed.

Incorporating 150-177 Relapsing/Remitting or Secondary/Progressive MS (RR/SPMS) patients, 100-110 Primary/Progressive (PPMS) patients and 152-210 controls.

No significant differences existed in allele frequencies between either MS group and controls for any of the InterLeukin microsatellite markers studied, nor were statistically significant differences observed in PPMS vs. RR/SPMS for any marker.

These data indicate that the IL-1, IL-2, IL-2Rß, IL-4, IL-9 and IL-10 Genes are unlikely to be susceptibility loci for MS in this population.

Objectives
Clinical reports have speculated on a more severe course of Multiple Sclerosis in patients with the Apolipoprotein E (apoE) Epsilon4 allele.

As this could be reflected by differences in the severity of tissue damage MRI was used to obtain further support for a disease modifying effect of the apoE genotype.

Methods
Brain MR scans of 83 patients (mean age 35.5 (SD 9.5 years) who participated in a cross sectional study on the distribution of Genotype patterns in Multiple Sclerosis.

The total Lesion Load on Proton Density weighted (T2-LL) and T1 weighted scans (T1-LL) obtained with conventional Spin Echo sequences at 1.5 T was measured.

A "Black Hole" ratio ((T1-LL/T2-LL)x100) was also calculated. This indicates the proportion of Multiple Sclerosis lesions with more severe tissue damage and may reflect disease aggressiveness or quality of repair.

Results
Patients with the apoE-Epsilon3/Epsilon4 Genotype (n=19) showed a non-significantly greater T2-LL (16.0 (SD 14.0) cm(3)) than patients with the Epsilon2/Epsilon3 (n=11; 13.3 (9.5) cm(3)) or the Epsilon3/Epsilon3 Genotype (n=49; 9.4 (SD 9.2) cm(3)).

Both the T1-LL (2.6 (SD 3.3) v 1.6 (SD 2.4) and 1.2 (SD 3.0) cm(3); p=0.04) and the Black Hole ratio (14.3 SD 11.9) v 7.4 (SD 9.3) and 8.4 (SD 13.3)%; p=0.02), however, were significantly higher in Epsilon3/Epsilon4 patients.

Similar differences were seen when comparing patients with at least one Epsilon4 allele with the remainder of the group.

Conclusions
These data support speculations on a modulation of Multiple Sclerosis severity by the apoE Genotype which can be attributed to more extensive tissue destruction or less efficient repair in carriers of the Epsilon4 allele.

Purpose
To assess the effects of Multiple Sclerosis (MS) on the patients' ability to fulfil their chosen family and social roles and to examine the impact of the disease on their relatives.

Methods
A population-based survey of all known patients with MS and their relatives in Hampshire County, England, between 1986 and 1989.

Results
Seventy-four% of the total study population of 411 completed the study.

The patients' mean age was 48.3 years (range 19-82) and the mean disease duration was 15.8 years. About 16% of patients were Depressed on a Mood Rating Scale and a similar number also exhibited symptoms of Anxiety.

The marital status of most patients had not changed since the onset of MS but 53% of those who were employed at the time of diagnosis gave up their jobs and the standards of living of 37% of patients and their families had declined as a direct result of the disease.

The ability to continue in gainful employment or to maintain social contacts and leisure activities correlated with the course and severity of the disease and Cognitive function.

Most carers reported symptoms that clearly related to organic pathologies, Anxiety and symptoms of Depression.

The occurrence of these symptoms was associated with disease severity. The professional career of 57% of relatives was also adversely affected by the patient's illness.

Conclusions
MS has a profound impact on the patients' social roles and their relatives' well-being. In contrast to previous studies, a high divorce/separation rate among patients with MS was not observed.

Severe Disability and Cognitive Impairment are predictors of loss of employment, decline in the standards of living and withdrawal from social and leisure activities among patients and are strong indicators of stress among relatives.

Studies with conventional Magnetic Resonance Imaging (MRI) support the hypothesis that Cognitive Impairment in Multiple Sclerosis (MS) patients is related with the lesion burden.

Patterns of Frontal Lobe Cognitive decline were also found to be related with the corresponding regional lesion load, although the total lesion load on T₂-weighted MRI scans of the Brain seems to be more relevant in determining Frontal Lobe deficits.

Other non-conventional MRI techniques with a higher specificity to the heterogeneous substrates of MS pathology, have recently been applied to MS Cognitive studies.

Such as the assessment of HypoIntense lesion load on T₁-weighted scans and the Histogram analysis of Magnetization Transfer Ratio (MTR) maps.

Results from these studies suggest that three factors play a role in the PathoGenesis of MS Dementia:

1. The burden of MS lesions
2. The severity of the pathological damage within individual lesions
3. The Normal-Appearing White Matter

In patients with MS Nocturnal Spasms (NPS) occur frequently, primarily during the night and may influence the ability to and/or quality of sleep. We enrolled in an open label trial with Gabapentin (GBP) (up to 600 mg/day) 24 MS patients with NPS.

We obtained patient reports of subjective discomfort at pre-treatment and following 2- (T1) and 8 weeks (T2), utilizing a 3-point analogue scale.

Twenty of the 22 patients who completed the study reported resolution or amelioration of discomfort. Clinical improvement occurred 1 - 5 days following initial treatment.

Three patients experienced adverse effects but completed the minimal follow-up period (2 weeks). Two patient dropped out of the study due to no compliance or adverse effects.

A very low dose of GBP may be effective treatment for MS patients with NPS who may benefit from rapid improvement of discomfort with minimal risk of adverse effects.

The Apoptosis-inducing effects of i.v. MethylPrednisolone were investigated as a possible method of controlling inflammation in the CNS in Adoptive Transfer-Experimental AutoImmune EncephaloMyelitis (AT-EAE) in Lewis rats.

Two pulses of MethylPrednisolone were given at the peak of mild and of severe disease. T-Cell Apoptosis was assessed on Spinal Cord cross-sections by morphology and TUNEL staining.

Concentrations of MethylPrednisolone were measured in Serum, CSF and Spinal Cord tissue by High-Pressure Liquid Chromatography (HPLC). In severe EAE, 10 mg/kg MethylPrednisolone increased T-Cell Apoptosis significantly and T-Cell infiltration was marginally decreased.

A maximal dose of 50 mg/kg MethylPrednisolone was superior in both respects and, in contrast to 10 mg/kg MethylPrednisolone, was also effective in mild EAE.

A dose of 1 mg/kg MethylPrednisolone did not produce notable changes compared with controls treated with Phosphate-buffered Saline.

Serum, CSF and Spinal Cord concentrations of MethylPrednisolone measured by HPLC 2 h after a single i.v. injection of 10 or 50 mg/kg MethylPrednisolone, revealed significantly higher MethylPrednisolone concentrations in severe EAE compared with mild disease.

With 50 mg/kg MethylPrednisolone, we obtained Serum and CSF concentrations in the region of 10(-5) M MethylPrednisolone.

We also studied the expression of Bcl-2, a typical Anti-Apoptotic regulatory protein, in T-Cells, and found no change after MethylPrednisolone treatment compared with controls.

MethylPrednisolone did not induce Apoptosis of Oligodendrocytes, which would have been an unwanted side effect in CNS Cells. This study provides evidence that MethylPrednisolone dose-dependently augments T-Cell Apoptosis in situ in AT-EAE.

Our results may have implications for the use of GlucoCorticoSteroids at very high doses in the treatment of Inflammatory Disorders of the CNS, such as Multiple Sclerosis, or of other target organs.