High Risk For Multiple Sclerosis Research Articles

Pediatric central nervous system inflammatory demyelination: acute disseminated encephalomyelitis, clinically isolated syndromes, neuromyelitis optica, and multiple sclerosis

We review the recent consensus definitions for acute disseminated encephalomyelitis,clinically isolated syndromes, neuromyelitis optica, and multiple sclerosis (MS) in children. We also discuss the importance of clinically defined consistency, the need for biomarker-based patient delineation, the likelihood of subsequent MS diagnosis following acute demyelination, and current therapeutic options. Studies of children after a first episode of demyelination have identified disease onset in adolescence, intrathecal oligoclonal bands and optic neuritis as associated with a higher MS risk, whereas prepubertal onset, presence of polyfocal features with encephalopathy, and transverse myelitis have been associated with a lower risk of subsequent MS. The relapsing-remitting form of MS accounts for over 96% of all MS in children. Neuromyelitis optica appears to be a distinct clinical and biological entity for which neuromyelitis optica IgG provides a high degree of specificity. Neuroimaging plays a key role in the diagnosis of acute demyelination, and serial imaging can provide evidence of lesion dissemination in time that can confirm a diagnosis of MS even in the absence of clinical relapse. Although clinical definitions, increased awareness, and MRI have contributed to the increasing identification of acute demyelination and MS in children, challenges remain in predicting MS risk. Identification of reliable biomarkers or application of more advanced neuroimaging techniques would serve as invaluable tools to distinguish monophasic demyelination from the first attack of MS.

Epidemiological investigations into multiple sclerosis in southern Hesse. II. The distribution of cases in relation to exogenous features.

In order to discover possible exogenous variables associated with a higher multiple sclerosis risk, the distribution of cases with definite and probable multiple sclerosis ascertained in the course of a micro-epidemiologic study in Southern Hesse was evaluated and compared with some environmental factors. The prevalence in 1980, the prevalence of cases with disease-onset within the region according to locality of onset and the rate of native Southern Hesse patients according to childhood residence all showed a similar geographical distribution, with the highest values in the south-eastern, mountainous part of the region. This district has a lower annual mean temperature, more annual snow-days and a higher annual precipitation compared to the remaining area. A statistical comparison revealed no association with industrial or agricultural activities, with a particular type of land use, with cattle, pig- or horse-breeding, or with sanitary or housing standards. On the other hand, a slight association with the soil type could be demonstrated, with higher rates on loam and clay subsoils when compared to predominantly sandy regions. Whether this finding has any significance or not remains to be clarified.

Multiple sclerosis in Gijon health district, Asturias, northern Spain

The objective of this study was to ascertain the prevalence and incidence of Multiple Sclerosis (MS) in a population of 33,775 in two primary health care centres in the sanitary district of Gijon, Asturias, northern Spain. Many information sources were used but the unique advantage of Gijon was that the city has a centralized computerized register of all diagnoses made for all consultations in the clinics and hospitals in the area. The HLA distribution in the population was already known and the Poser classification of MS was used. The crude MS prevalence was 65/100,000, a similar prevalence to that found in southern and eastern Spain, Sicily and Greek-speaking Cyprus. The mean incidence was 3.7/100,000 per year. The study demonstrated the advantage of a centralized and computerized medical recording system and demonstrates that northern Spain is a moderately high or medium MS risk zone.

The contribution of cerebrospinal fluid oligoclonal bands to the early diagnosis of multiple sclerosis

Background McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings. Objective To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice. Methods We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB). Results We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI. Conclusion OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.

Demyelinating Optic Neuritis in Children

Acute demyelinating optic neuritis in children can occur in isolation or be associated with acute disseminated encephalomyelitis, multiple sclerosis, or neuromyelitis optica. Clinical features, neuroimaging, cerebrospinal fluid findings, and long-term prognosis were reviewed in 26 children diagnosed with optic neuritis at the first presentation of demyelinating disease. The risk factors for the subsequent diagnosis of multiple sclerosis were analyzed. The mean duration of follow-up was 6.2 years. To date, 6 children have been diagnosed with multiple sclerosis (23%). An abnormal brain magnetic resonance imaging, older age, oligoclonal bands in cerebrospinal fluid, and elevated immunoglobulin G index were associated with multiple sclerosis outcome. Children with monosymptomatic optic neuritis and an abnormal brain magnetic resonance imaging had a higher risk for multiple sclerosis. These children should be monitored closely for the subsequent diagnosis of multiple sclerosis and can be considered for early preventive therapy.

Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event

Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in naïve CD4(+) T cells from 37 CIS patients at time of diagnosis and after 1 year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into four distinct subgroups. A subset of 108 genes further discriminated patients in one of these (group 1) from other CIS patients. Remarkably, 92% of patients in group 1 converted to CDMS within 9 months. Consistent down-regulation of TOB1, a critical regulator of cell proliferation, was characteristic of group 1 patients. Decreased TOB1 expression at the RNA and protein levels also was confirmed in experimental autoimmune encephalomyelitis. Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence, possibly resulting in earlier activation of pathogenic CD4(+) cells.

Factors in the rising prevalence of multiple sclerosis in the north-east of Ireland

Background Northern Ireland is recognized as an area of high risk for multiple sclerosis. The original study of Allison and Millar in 1951 found a prevalence of 51/100,000 and mean annual incidence of 2.74/100,000/year. Subsequent studies in 1961, 1986, and 1996 suggested rising prevalence – 80, 138, and 168.2/100,000, respectively. Methods In 2004, we surveyed the North-East of Northern Ireland (population 160,446, area 2030 km2) using multiple sources of case ascertainment, all satisfying the Poser criteria for definite or probable multiple sclerosis (MS) or the McDonald criteria. Results From a provisional list of 469 cases, 370 (123 males, 247 females) were identified. The prevalence was 230.6 per 100,000 (95% CI 207.0–255.4) with significantly higher prevalence in females (300.8/100,000) than males (157.0/100,000). Direct standardization to the 1961 Northern Ireland population reduced the overall prevalence rate to 200.5/100,000 (95% CI 193.2–208.0), in females to 270.2/100,000 (95% CI 258.8–282.4) and in males to 131.1/100,000 (95% CI 122.8–139.9). In 1996, incidence had risen to 9.3/100,000/year (14 cases in population of 151,000) with a higher incidence in females (10.3/100,000/year) than males (8.3/100,000/year). Conclusions Northern Ireland continues to have a rising prevalence of MS. The increase in incidence suggests a true increase in the disease.

Smoke exposure increases the risk for multiple sclerosis

To estimate the effect of exposure to smoking on the risk for multiple sclerosis (MS), we analyzed nicotine metabolite (cotinine) levels in biobank samples from 109 MS cases and 218 matched referents. Elevated cotinine levels, even modest elevations, were associated with an increased risk for MS (all other categories versus lowest: OR = 2.9; 95% CI: 1.3-6.3). A similar but non-significant risk increase was observed also in the small subset of individuals with samples collected before the onset of MS (all other categories versus lowest: OR = 2.4; 95% CI: 0.26-21). Elevated cotinine was associated with an increased risk for MS predominantly in women (all other categories versus lowest category: OR = 3.9; 95% CI: 1.3-12), whereas the risk increase in men was smaller and non-significant. Smoke exposure is associated with a higher risk for MS than previously estimated. There seems to be a threshold effect present in the lower range of cotinine in its relation to MS. Modestly elevated cotinine levels suggestive of passive smoking are associated with an increased risk for MS. Smoke exposure may explain the higher incidence of MS in women. These preliminary findings need to be confirmed in an expanded material of prospectively collected samples.

A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10

Multiple sclerosis (MS) is a neurodegenerative disease of uncertain etiology. In MS, neurodegeneration is thought to be secondary to autoimmune-mediated damage. However, no cohesive explanation yet exists as to how environmental factors interact to induce a neurodegenerative autoimmune response. Insufficient sunlight exposure and chronic viral infections have been proposed as unrelated environmental risk factors for MS. We suggest that these risk factors may act synergistically to enable the pathogenic autoimmune response. Low ultraviolet light (UVL) exposure depletes vitamin D3 stores, and low vitamin D3 levels correlate strongly with high MS risk. The central nervous system converts vitamin D3 into 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), a biologically active hormone with anti-inflammatory and neuro-protective functions that depend on IL-10-producing regulatory lymphocytes. Herpesvirus infection also correlates with MS risk. Some herpesviruses like Epstein-Barr virus produce an IL-10-like cytokine termed vIL-10. We hypothesize that vIL-10 may induce a dysfunction of IL-10-producing regulatory lymphocytes, thereby undermining the protective functions of sunlight, vitamin D3, and 1,25-(OH)2 D3. The vIL-10 could elicit a host immune response capable of neutralizing or depleting IL-10, or the vIL-10 could compete with IL-10 but fail to perform an essential IL-10 function. In either case, the lack of sunlight exposure and the herpes virus infection might synergize to induce a defect in IL-10-producing regulatory lymphocyte function that undermines self-tolerance mechanisms and enables a pathogenic autoimmune response to neural proteins.

Electrophysiological Evidence for Heterogeneity of Lesions in Optic Neuritis

To examine the natural history of multifocal visual evoked potentials (mfVEPs) within 12 months of the first episode of optic neuritis (ON) in patients with possible multiple sclerosis (MS). Twenty-seven patients with a first episode of ON, no previous demyelinating events, and MRI lesions consistent with demyelination were examined with mfVEP. Changes in amplitude and latency of mfVEP were analyzed at 1, 3, 6, and 12 months after an acute attack. Five of 27 patients had persistent loss of amplitude after 12 months of follow-up. This loss was most marked centrally. Amplitude recovered in the remaining 22 patients at 1 month, but delayed latency, which was also most marked centrally, persisted. Of these, two distinct subgroups were identified: six patients with no improvement in latency and 16 patients with significant latency recovery over the 12 months of follow-up, suggesting remyelination. Conversion to MS was highest in the group with severe amplitude loss, followed by the group with no latency recovery. The conversion rate was lowest in the group of patients with latency improvement. Distinct patterns of disease evolution were identified using mfVEP in patients with first episode of optic neuritis and at high risk for MS, supporting the concept of heterogeneity of early lesions in MS.

Incidence and prevalence of multiple sclerosis in Saskatoon, Saskatchewan

To determine the incidence of multiple sclerosis (MS) in a longitudinal surveillance over 35 years and to estimate the prevalence rate in Saskatoon, Saskatchewan, on January 1, 2005. A population-based registry was established in 1969, and identification of cases continued to 2005, from medical records, physicians, neurologists, community and provincial resources. A modified classification of Allison and Millar and the Schumacher diagnostic criteria were originally applied, and patients with definite and probable MS were included. The rates were age- and sex-adjusted to the US, European, and world 2000 populations. From 1970 to 2004, there were 558 incidence cases identified, 402 women and 156 men, for a sex ratio of 2.6:1 The average annual incidence rate was 9.5 in 100,000 (95% CI 8.8 to 10.4) and was stable over the three decades. The innate risk or residence at onset rate was 197 in 100,000 (95% CI 170 to 226). The crude prevalence rate for the living 587 cases on January 1, 2005, was 298.3 in 100,000 (95% CI 274.7 to 323.6). The incidence and prevalence rates adjusted to the standardized populations were statistically higher than the longitudinal European studies and similar to North American studies. Our incidence study confirms the high risk of multiple sclerosis (MS) in Saskatoon, and these rates seem to be stable over the past 35 years. The high crude prevalence rate results from an accumulation of incidence and nonresident cases over time. Long-term follow-up studies and comparison with standardized populations are recommended to estimate reliable incidence and the true risk of MS in the world.

Parental smoking at home and the risk of childhood-onset multiple sclerosis in children

The possibility of a link between active smoking and incident multiple sclerosis (MS) has been raised. However, possible links between incidence of MS and passive smoking, particularly in children, have not been analysed. We conducted a population-based, case-control study. The cases were patients with incident MS occurring between 1994 and 2003, before the age of 16 years, in France. Each case was matched for age, sex and geographic origin with 12 controls, randomly selected from the French general population. Information about the smoking history of the parents of the cases and controls was collected with a standardized questionnaire. Conditional logistic regression was used to estimate the rate ratio (RR) of MS associated with parental smoking at home. The 129 cases of MS were matched with 1038 controls. Information about parental smoking was obtained for all these cases and controls. Exposure to parental smoking was noted in 62.0% of cases and 45.1% of controls. The adjusted RR of a first episode of MS associated with exposure to parental smoking at home was 2.12 (95% confidence interval: 1.43-3.15). Stratification for age showed that this increase in risk was significantly associated with the longer duration of exposure in older cases (over 10 years of age at the time of the index episode)-RR 2.49 (1.53-4.08)-than in younger cases. Children exposed to parent smoking have a higher MS risk. The duration of exposure also affects the level of risk.

Allergy, family history of autoimmune diseases, and the risk of multiple sclerosis

Previous reports suggested an association between allergy, autoimmunity, and risk of multiple sclerosis (MS), but results have been inconsistent. The present study assessed the association between history of allergy and autoimmune diseases, and the risk of MS. We conducted a case-control study nested in the Nurses' Health Study (NHS) and NHS II cohorts. A total of 298 women with MS were matched with 1248 healthy controls and 248 women with history of breast cancer. A mailed questionnaire gathered information about history of allergic conditions and autoimmune disorders. History of allergy was not associated with MS risk [odds ratio (OR) 1.0, 95% confidence interval (CI) 0.8-1.4]. As expected, cases were more likely to have a positive family history of MS than controls (OR 9.7, 95% CI 6.1-15.3). A modest association was found between family history of other autoimmune diseases and MS risk (OR 1.4, 95% CI 1.0-1.8). We obtained similar results when we used women with breast cancer as comparison group. Family history of other autoimmune diseases was associated with a higher MS risk, suggesting a common genetic background or shared environmental triggers. There was no clear association between personal history of allergy and risk of MS.

Clinically isolated syndromes

Multiple sclerosis (MS) represents a spectrum of demyelination that depends on disease duration and clinical categorization. Most patients present with the relapsing-remitting form of the disease. The earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). Predicting which CIS patients are at high risk for MS is complicated by the disparity between clinical attacks and the extent of axon pathology. However, recent interferon-beta (IFN-beta) trials have demonstrated a delay in time to the second demyelinating event with early treatment, and early treatment could also slow the progression from RRMS to secondary-progressive MS (SPMS). Clinical findings in combination with brain MRI and CSF analysis can be used in CIS patients to evaluate their risk for clinically definite MS (CDMS). Application of the McDonald criteria also allows an earlier MS diagnosis by using new MRI lesions to define dissemination in time. Early immunomodulatory therapy for selected CIS patients may eventually prevent future axon pathology and progression of disability in this lifelong disease.

Données épidémiologiques et analyse de‘l’offre de soins de la sclérose en plaques en France

According to the available previous studies, France is considered a zone of medium to high risk of multiple sclerosis (MS) with an estimated overall prevalence of at least 50/100,000 inhabitants, incidence rates were stable in some areas but increased over time in others and a strong ethnic effect on the incidence, clinical presentation, and course of MS is reported. Based on two health insurance survey the prevalence has been deduced. At January 1, 2003 from the data of agricultural health insurance the prevalence is evaluated at 65.5/100,000 inhabitants (95p.cent CI=62.5-67.5) with a gradient of North East towards South-West. The data from the national health insurance were very near. During the period 2000-2004, recent studies in Auvergne and Brittany demonstrated an annual incidence comprising between 4.2 and 5.1 per 100,000 inhabitants. In Lorraine, in a large population-based study, in December 31, 2004 the prevalence rate was 120/100,000 (95p.cent CI: 119 to 121). During the period 1990-2002, the average age- and sex-adjusted annual incidence rate was 5.5/100,000 (95p.cent CI: 4.4-6.6). In Lorraine, we found that the age-adjusted incidence rate increased during the period 1990-2002. The incidence of MS in women increased, whereas that in men did not change significantly during this period. Similarly, in Norway, North Ireland and Denmark, the incidence among women increased the most. The clinical features of MS were compared in 211 North Africans patients and 2 945 Europeans patients in two French MS centres (Lorraine and Nice) with definite MS according to McDonald's criteria. The course of MS appears more aggressive in North Africans than in Europeans patients. For example, we demonstrated a shorter time to reach the Expanded Disability Status Scale score of 4.0 (p=0.001) or 6.0 (p<0.0001) in North Africans patients. The incidence rates found in these studies were comparable to those reported in several European populations. This undoubtedly places France in the category of regions with a high risk zone of MS. The incidence of MS in women increased; thus, exogenous (or epigenetic) factors vary over time and may affect men and women differently. The course of MS appears more aggressive in North Africans than in Europeans patients.

Identification of fibers at risk for degeneration by diffusion tractography in patients at high risk for MS after a clinically isolated syndrome

Focal inflammatory/demyelinating lesions are thought to be the source of Wallerian degeneration or other injury to local, transiting fiber tracts in the brain or spinal cord in multiple sclerosis (MS). A methodology is established to isolate connections between focal demyelinating lesions and intersecting fibers to permit explicit analyses of the pathology of secondary fiber injury distant from the focal lesion. A strategy is described and feasibility demonstrated in three patients with a clinically isolated syndrome and positive MRI (at high risk for MS). The strategy utilizes streamtube diffusion tractography to identify neuronal fibers that intersect a focal lesion and pass through a region of interest, in this case the corpus callosum, where distal (to focal lesion) interrogation can be accomplished. A sizeable fraction of the normal appearing white matter (NAWM) in the early stages of disease can be defined in the corpus callosum, which is distinctive in that this tissue connects to distant demyelinating lesions. The new class of tissue called fibers-at-risk for degeneration (FAR) can be identified and interrogated by a variety of quantitative MRI methodologies to better understand neuronal degeneration in MS.

Not Every Patient With Multiple Sclerosis Should Be Treated at Time of Diagnosis

D ISEASE-MODIFYING agents approved for treatment of patients with multiple sclerosis (MS) are glatiramer acetate, interferon beta-1b and -1a, and mitoxantrone hydrochloride. Natalizumab was Food and Drug Administration approved in November 2004, but the manufacturers suspended marketing and clinical trials in 2005 because of safety concerns. Interferon beta-1a is approved for individuals with clinically isolated syndromes (CISs) who are at relatively high risk to “convert to MS.” Opinions vary about whom and when to treat. On one hand, the Medical Advisory Board of the National Multiple Sclerosis Society consensus statement (updated in February 2005) recommends initiation of a disease-modifying agent “as soon as possible following definite diagnosis of MS with a relapsing course, and in selected patients with first attack who are at high risk for MS (CIS).” Alternatively, the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines suggest “it is appropriate to consider” treatment with approved therapies in these patients. We do not believe that all patients with MS or CIS should begin indefinite treatment at the time of diagnosis. Until it is clear that the patient has continuing disease activity clinically and/or radiologically, in which case the need for treatment is clear to the physician and to the patient, it is advisable to observe a period of no treatment while monitoring for inflammatory disease activity. The final decision about whether and when to initiate treatment should be shared by the patient and physician after an unbiased review of the relevant information with the patient. Our current approach is predicated on the following: (1) MS often has a favorable natural history; (2) disease-modifying drugs are only partially effective in the short-term and prevention of disability in the long-term is unproven; (3) with prolonged treatment, it is hard to distinguish whether a favorable outcome reflects a favorable natural history or successful treatment in an individual patient, especially if treatment is started without a period of observation; (4) expense, adverse effects, and neutralizing antibodies are a concern and patients may be reluctant to commit to long-term parenteral medications, especially within the first few months following diagnosis; and (5) prospective clinical and magnetic resonance imaging (MRI) monitoring may allow identification of patients who need treatment. Because disease-modifying agents do not benefit patients with primary progressive MS (approximately 10% of all patients with MS) and their benefit in secondary progressive MS (approximately 30% of all patients with MS) remains questionable, this discussion is limited to patients with a diagnosis of relapsing-remitting MS and CIS. Patients with MS often do well without any treatment. A recent Olmsted County, Minnesota, study found that patients with minimal or nodisability(ExpandedDisabilityStatus Scale [EDSS] score 2) at more than 10 years from onset have a 90% chanceofremainingfullyambulatory (EDSSscore 3.0)10yearslater. This group accounted for 17% of all patients with MS or 33.3% (28/94) of patientswith relapsing-remittingMS in that population-based cohort. Kurtzke et al reported similar findings. Extrapolating these data to all patientswith“destined tobebenign” MS in the United States would result in approximately 35 870 individuals (17% of 211 000 patients with MS in the United States) unnecessarily receiving a potentially lifelong medication. Currently available approved treatments offer a mild to moderate short-term benefit in individuals with active recent disease who are most likely to respond. However, long-term efficacy is unproven. One needs to treat 5.6 patients with interferon beta-1b, 6.3 with interferon beta-1a, and 14.3 with glatiramer acetate to generate 1 person free of relapse for 2 years. Reduction in relapse rate is most evident in the first year and then declines. Number needed to treat (NNT) estimates for natalizumab are more favorable; early results suggest that the NNT to render 1 patient relapse free after 2 years of therapy is 2 to 2.4. However, serious safety concerns have led to voluntary cessation of natalizumab production. Author Affiliations: Department of Neurology, Mayo Clinic, Rochester, Minn (Drs Pittock, Weinshenker, Noseworthy, Lucchinetti, Keegan, and Rodriguez), Scottsdale, Ariz (Drs Wingerchuk and Carter), and Jacksonville, Fla (Dr Shuster).

MULTIPLE SCLEROSIS IN THE TROPICS

Objectives: Multiple sclerosis (MS) is not commonly seen in children, more so amongst Asian children living in the tropics. We report four cases of definite relapsing-remitting multiple sclerosis, and a fifth child with a florid first demyelinating episode and a high risk towards developing subsequent MS, occurring in Malaysian children. Methods: Five children were seen over the last three years (January 2003 till October 2005). The children with definite MS fulfilled MacDonald's criteria for dissemination in time and space, whilst the child with high risk for MS fulfilled criteria for dissemination in space. Results: Age of onset ranged from 4 to 10 years. All four children (two girls, two boys) with definite MS had an initial optic neuritis of insidious onset, followed by subsequent symptomatic and silent demyelinating syndromes involving the brain and spinal cord. Long segment contiguous lesions were seen when the spinal cord was involved. Clinical symptoms included deterioration in vision, aphasia, cerebellar dysfunction, hemiparesis, monoparesis or quadriparesis, paraparesis and sphincteric involvement. All clinical episodes improved with intravenous methylprednisolone and oral prednisolone. The first child we saw had five relapses before receiving prophylactic interferon beta-1a, experiencing a further single relapse after a year on treatment. Two other children have recently been started on interferon beta-1a after the second episode. The boy with high risk for MS had a first demyelinating episode with bilateral optic neuritis and multiple gadolinium enhancing perpendicular periventricular and callosal lesions, with complete resolution after treatment with steroids. Conclusion: Multiple sclerosis is seen in Asian children. The disease in these children may have a preponderance towards optic neuritis and spinal cord syndromes.

Divergent risk of multiple sclerosis in two anabaptist communities in America

A lowered risk of multiple sclerosis (MS) has been reported in the Hutterite community residing mainly in southern Canada. In another anabaptist community, the Old Colony Mennonites (OCM), settled in Canada and spread to Latin America, only a large pedigree with an increased risk of autoimmune diseases, including type I diabetes and three cases of MS, was reported. The prevalence of MS in the pedigree (3,158 per 100,000), even when observing its confidence interval, seems rather high, and the MS prevalence in the Mennonite general population is assumed at least to be equal to the Canadian rates. Based upon an extended study of the literature, the hypothesis that smoking and curing with nitrate/nitrite plays any role, by interaction with inflammatory intestinal changes in childhood infections, is supported. In addition, tobacco smoking and short-term breast-feeding as possible risk factors are also in line with a higher MS risk in OCM, whereas insecticides and herbicides can be excluded as risk factors in MS.

Risk for multiple sclerosis in dizygotic and monozygotic twins

We investigated the risks of twins for multiple sclerosis (MS). Our data are linked registers of all Danish twins and of all Danes born between 1920 and 1970 in whom MS was diagnosed before 1997. We compared differences in the risks for MS by Cox regression and standardized incidence ratios. Our analyses suggest that dizygotic twins have an approximately 60% lower risk for MS than monozygotic twins and a 20% lower risk than singletons. Monozygotic twins appear to have a somewhat higher risk for MS than singletons albeit not statistically significant. We offer no biological explanation for our findings, but suggest that either sharing fetal life with a genotypically different individual is beneficial for the immune system or that there is a linkage between the genes that influence dizygotic twinning and other genes that protect against MS.