Evaluation Of InterLeukin Genes Fails To Identify Clear Susceptibility Loci For MS
McDonnell1 GV, Kirk1 CW, Hawkins SA, Graham CA
J Neurol Sci 2000 May 1;176(1):4-12
Royal Victoria Hospital, Northern Ireland Neurology Service, Northern Ireland, Belfast, UK
PMID# 10865086; UI# 20325114
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.
Apolipoprotein E Genotype Related Differences In Brain Lesions Of Multiple Sclerosis
Fazekas F, Strasser-Fuchs S, Schmidt H, Enzinger C, Ropele S, Lechner A, Flooh E, Schmidt R, Hartung HP
J Neurol NeuroSurg Psychiatry 2000 Jul;69(1):25-28
Karl-Franzens University, Dept of Neurology, Auenbruggerplatz 22, A-8036 Graz, Austria
PMID# 10864599; UI# 20323419
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.
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.
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.
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.
The Social Impact Of Multiple Sclerosis - A Study Of 305 Patients And Their Relatives
Hakim EA, Bakheit AM, Bryant TN, Roberts MW, McIntosh-Michaelis SA, Spackman AJ, Martin JP, McLellan DL
Disabil Rehabil 2000 Apr 15;22(6):288-93
Southampton General Hospital, Rehabilitation Research Unit, Southampton, UK
PMID# 10864132; UI# 20320128
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.
A population-based survey of all known patients with MS and their relatives in Hampshire County, England, between 1986 and 1989.
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.
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.
MRI Correlates Of Cognitive Dysfunction In Multiple Sclerosis
Rovaris M, Filippi M
J NeuroVirol 2000 May;6 Suppl 2:S172-5
Scientific Institute, Ospedale San Raffaele, NeuroImaging Research Unit, Dept of NeuroScience, via Olgettina 60, 20132 Milan, Italy
PMID# 10871808; UI# 20332485
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:
- The burden of MS lesions
- The severity of the pathological damage within individual lesions
- The Normal-Appearing White Matter
Gabapentin Is Effective In Treating Nocturnal Painful Spasms In Multiple Sclerosis
Solaro C, Uccelli MM, Guglieri P, Uccelli A, Mancardi GL
Mult Scler 2000 Jun;6(3):192-3
Italian M.S. Society, Dept of Social and Health Services and Research, Italy
PMID# 10871832; UI# 20332499
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.
T-Cell Apoptosis In Situ In Experimental AutoImmune EncephaloMyelitis Following MethylPrednisolone Pulse Therapy
Schmidt J, Gold R, Schonrock L, Zettl UK, Hartung HP, Toyka KV
Brain 2000 Jul;123(Pt 7):1431-1441
Univ of Wurzburg, Dept of Neurology, Clinical Research Group for Multiple Sclerosis and NeuroImmunology, Germany
PMID# 10869055; UI# 20327429
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.