Relatives Of Multiple Sclerosis Patients Research Articles

Frequency of Multiple Sclerosis (MS) Among Relatives of MS Patients in Hamadan Society, Iran

Frequency of Multiple Sclerosis (MS) Among Relatives of MS Patients in Hamadan Society, Iran

P014 - Genetics of MS in Saudi Arabia

Pathogenesis of multiple sclerosis (MS) is poorly understood, evidence suggests that genetic and environmental factors may play substantial roles in disease development. The role of genetics is evident by many reports showing familial aggregation of the disease, high concordance rate among twins, association with MHC and the increased risk among relatives of MS patients. Genome-wide association studies (GWAS) showed an association between subset of single-nucleotide polymorphism (SNPs) and multiple sclerosis. The Saudi community is a very young population where 54% are below the age of 18 years. It is characterized by large family size and prevalent consanguineous marriages. The incidence and prevalence of multiple sclerosis have been increasing in the last few years regionally in Saudi Arabia and it is expected from demographics point view to further increase. In our local registry we have found that 21% of our patients reported having at least one relative affected. It is not clear if parental consanguinity has any role in non-genetic diseases, especially those with an expected genetic predisposition such as MS. We have reported that parental consanguinity might be a risk factor for familial multiple sclerosis. WE have studied and reported the common association of single-nucleotide polymorphism (SNPs) and multiple sclerosis by Genome-wide association studies (GWAS). We found that SNPs rs6498169 and 10984447 are the two most significant multiple sclerosis linked SNP in our Saudi MS population outside the MHC region. Our results suggest that it is possible to use a more homogenous genetic pool to identify the most significant MS-linked SNPs in the Saudi population, even with a very small sample size. Our finding is in agreement with many other studies that used much larger sample sizes and were performed in many ethnic groups. These data has encouraged us to further study the genetic basis of MS in the Saudi MS patients. Our ongoing investigations included using whole genome, high-resolution array comparative genomic hybridization (array CGH) of variations in genomic dosage compared to the normal reference dosage within FMS cases as well as Hall exon sequencing and studying the MHC region by junior sequencing of the HAL region. We will present the initial data from two large families.

Retinal nerve fiber thickness and MRI white matter abnormalities in healthy relatives of multiple sclerosis patients

ObjectivesTo compare retinal nerve fiber (RNFL) thickness and conventional and non-conventional MRI characteristics of healthy controls (HCs) from the general population (non-fHC) to healthy relatives of multiple sclerosis (MS) patients (fHC). MethodsSixty-eight (68) HCs underwent optical coherence tomography (OCT) and 3T MRI examination. Subjects were classified based on whether or not there was a family history of MS. The study enrolled 40 non-fHC who had no relatives with MS and 28 fHC with at least one relative affected with MS. The associations between OCT parameters and conventional and non-conventional MRI measures were investigated. ResultsThere were no significant OCT or conventional and non-conventional MRI measureable differences between the non-fHC and fHC groups. Periventricular localization and total volume of white matter (WM) signal abnormalities (SA) were more common in the fHC group but the differences did not reach a level of significance. A significant association between decreased RNFL thickness with increased volume (p=0.001), number (p=0.003) and frequency of ≥9 T2 (p=0.003) WM SAs on MRI was found in the fHC group. No association between OCT and MRI parameters was detected in the non-fHC group. ConclusionThere is an association between decreased RNFL thickness on OCT and increased WM injury in healthy relatives of MS patients. Further studies should explore the pathophysiology of these findings.

MS and autoimmune disorders

The paper in this issue from Hemminki courageously takes on the thorny question of the co-association of multiple sclerosis (MS) with other diseases, a query which has had more than a few prior attempts at resolution. A priori, this is not an easy question to answer since MS is not all that common, and many of the diseases which have been sought for co-association are even less so. Among ways to attenuate the problems, the most important are ensuring adequate sample size and controlling for ascertainment. Scandinavian registries are to be envied as on their own they make a strong case for national health delivery. These in particular have been systematically available for study. Hemminki et al. provide a large sample for scrutiny and employ it to conclude that MS is associated with autoimmune and “related” disorders. The dataset is large, the approach is sound, and the investigators are experienced and reliable. The direction of ascertainment, i.e., coming from the autoimmune side, and case-finding for MS is novel and attractive and is complementary to existing studies. There are, however, reasons for misgivings despite my admiration for the authors and their methodology, and this has to do with interpretation of the results. Ascertainment on the basis of hospital admission may select for more severe cases depending on local custom for diagnostic lumbar puncture with geographic variation. It might be that even these may have changed from the previous generation to the present, but both are included in the study. Pooling MS and “related” disorders raises two issues. The first is that adding in cases of familial MS perhaps should not be used to support the argument of co-association as the authors have done. This will surely seem to some a circular argument—increased frequency of MS in the relatives of MS patients is being used to support the thesis that MS is related to autoimmune diseases. Familiality of MS has long been known. The authors, having made a distinction between MS and “related” disorders, perhaps unwittingly merged both into autoimmunity in their discussion. They are so counted in a claimed relative risk of 1.21 for autoimmune disease among the relatives of those with these conditions. Removing MS and amyotrophic lateral sclerosis (ALS) from the numbers subtracts 139 cases or 12.7% of the total of 1,087 cases identified, eliminating the proposed 1.21× excess of “autoimmunity.” Taking out the asthma inclusion from the ranks of the “autoimmune and related” as well leaves a reduction—not the increase proposed. The inclusion of ALS and asthma does strain the limits of orthodox contemporary concepts of these disorders. It would help to be reassured these inclusions were not made post hoc when the data were found not to fit a prior hypothesis. There is very little evidence that ALS is autoimmune in nature, and asthma seems primarily more in the allergy line with tenuous connections to autoimmunity. It is possible that the ALS findings result from the inclusion of cases of chronic myelopathy (many of whom had MS) from a previous generation especially when upper extremity atrophy was present or spondylosis coexisted. On the other hand, the one thing that MS and ALS do share is progressive central axonal degeneration.

Proton magnetic resonance spectroscopy of normal appearing white matter in asymptomatic relatives of multiple sclerosis patients

Proton magnetic resonance spectroscopy of normal appearing white matter (NAWM) was performed in 25 first-degree relatives of patients with multiple sclerosis (MS). In relatives of MS patients, insignificant trends in the NAA/Cho ratio (to be lower) and in the Cho/Cr ratio (to be higher) were found when compared with healthy controls. These results demonstrated that there are only minimal, insignificant changes in commonly identified metabolite concentrations in NAWM of relatives of MS patients when compared with healthy subjects.

Enfermedades autoinmunes y esclerosis múltiple

Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system with an unknown origin, although the immunological system plays a crucial role in its pathogenesis. It has been observed that the relatives of MS patients very often have other autoimmune diseases (ADs) and it has been suggested that there may be susceptibility genes that are common to this group of diseases.Our aim was to estimate the prevalence of ADs in first and second degree relatives of patients with MS and to determine the coexistence of other ADs in MS patients.We selected 251 patients with MS defined by the Poser criteria and face-to-face interviews with the patients and/or their relatives were conducted to investigate the following ADs: MS, rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, autoimmune thyroid disease (ATD), inflammatory bowel disease, myasthenia gravis, type I diabetes mellitus (DMI) and psoriasis. RESULTS. 29.9% of the patients with MS had a first and/or second degree relative with an AD. Prevalence of ADs in first degree relatives was 15.5%, 30% in familial MS and 40% if the patient had both MS and another AD. The most frequent ADs were: MS 27%, psoriasis 18%, ATD 16% and DMI 15%. 15 patients had MS and another AD: six ATD, three DMI, four psoriasis, one inflammatory bowel disease and one myasthenia gravis.These findings lend support to the existence of susceptibility genes that are common to the different ADs and would act as risk factors.

Familial recurrence rates and genetic models of multiple sclerosis

Susceptibility to multiple sclerosis (MS) is determined by both inherited and non-inherited factors. The importance of genetic factors is demonstrated by the increased risk of disease in relatives of MS patients. Our objective was to determine the implications of the observed familial recurrence risks for the genetic basis of MS. We developed a computer program which calculates recurrence risks for monozygotic (MZ) twins, siblings, and second degree relatives, and used it to calculate recurrence risks for a wide variety of genetic models. We investigated models with different numbers of genes, different patterns of interaction between the genes, and dominant or recessive inheritance. The models that best reproduced the observed values had multiple loci with strongly synergistic interaction and autosomal dominant (AD) inheritance. At least six loci were required, and we found no upper limit on the number of loci. Models with genetic heterogeneity, where only a fraction of the risk loci are required for disease, are possible. In models with large numbers of loci the "abnormal" alleles conferring risk of disease are the most common allele. We conclude that a variety of genetic models with multiple genes, dominant inheritance, and synergistic interaction between risk genes are consistent with the observed familial recurrence rates in MS.

Home care by and for relatives of MS patients.

Relatives and family members are the core of the care provided in the home. This also applies to relatives of multiple sclerosis (MS), patients who are dependent on assistance by others. If we want to keep the system of home care going, nurses must keep these care-providing relatives on their feet. We can only do this if we give timely support to these relatives in carrying out their care task and the problems that may arise from it. Once the relatives are overburdened, help is too late. Thus, prevention is an important task for home care nurses. It is crucial that the support the nurses offer fits the specific chemistry of MS patients and their relatives; their efforts will therefore be substantial.

Genetic epidemiology of multiple sclerosis: a survey.

The possible role of genetic factors in the etiology of multiple sclerosis (MS) has been debated for over a century. It is now clear that genetic and environmental interactions must exist. It is likely that MS susceptibility is under the control of several genes encoded both within and outside the major histocompatibility complex (MHC). It is therefore unlikely that MS has a purely transmissible cause for these and other reasons, including the low concordance rate in dizygotic twins, low concordance rate in conjugal pairs, negative birth order in multiplex MS sibships, the relatively high rate of MS in second- and third-degree relatives of MS patients, and the identification of groups resistant to MS in otherwise high-risk areas.

Evoked potential testing in relatives of multiple sclerosis patients

Evoked potential (EP) tests were obtained in 110 neurologically normal first-degree relatives of patients with multiple sclerosis. Visual EP tests were performed in all relatives; brainstem auditory and median nerve somatosensory EP tests were performed in 67 relatives. The relatives had a mean visual EP P100 latency that was significantly longer than that for normal subjects controlled for age and gender. Asymmetries were seen in results from individual MS relatives, including interocular visual EP P100 differences of up to 14 ms, and interarm somatosensory Erb-N18 differences of up to 3.0 ms. We identified 19 pairs of patients and relatives who were HLA identical and 18 other pairs who were HLA double nonmatched. EP asymmetries were seen more often in the HLA identical siblings than in the HLA double patients, especially if they share HLA types with the patients. Since less than 2% of siblings of MS patients would be expected to eventually develop clinical MS, these small subclinical electrophysiological changes are not expected to be a sign of the future appearance of clinical MS. Clinicians should be aware not to overinterpret small EP changes in relatives of MS patients.

Anomalous lymphocyte-antigen reaction in relatives of multiple sclerosis patients. A study of a possible genetic factor in the disease.

A combined familial study of multiple sclerosis (MS) in England and in the Rostock area of the GDR using the macrophage electrophoretic mobility (MEM)-LAD test embracing 132 relatives has revealed a closely similar pattern of distribution of "anomalous" LAD (Linoleic Acid Depression) values in relatives (77% type of reaction) to that originally reported in the British study. The anomaly in predominantly associated with females--all mothers of MS patients being affected, whilst daughters and sisters are also represented. In addition unusual full MS type of reaction (90% reduction) has been found in some children related to patients. There is clearly a genetic element in the development of MS probably mainfested in the inborn mishandling of unsaturated fatty acids suggested by Thompson; no recognizable pattern of inheritance is noticeable even within the combined material. There is evidence that the metabolic anomaly alone does not inevitably lead to MS, and the full abnormality may be present at an early age. A survey about the examinations and a selection of characteristic family trees of MS are given, illustrating the manner in which the 77% type anomaly is distributed with occasional omission of a generation.

HLA haplotypes in families with high frequency of multiple sclerosis.

Eight families from southern Sweden having two or more members with multiple sclerosis (MS) were typed for various alleles of the HLA system. The MS patients within each family shared one major histocompatibility system (MHS) haplotype, which was identical to the hitherto-described MS-associated haplotype A3B7Dw2 only in two of the families. Healthy relatives of MS patients were often found to carry the same haplotype as the affected members, which makes an estimate of the degree of penetrance of disease in individuals carrying the MS-predisposing MHS-linked gene possible.