Pregnancy,delivery and birth outcome in different stages of maternal multiple sclerosis

To investigate the influence of maternal multiple sclerosis (MS) on pregnancy, we compared pregnancy, delivery and birth outcome in births prior to onset of MS (pre MS), between MS onset and diagnosis (early MS), and after diagnosis of MS (manifest MS). Mothers with MS were identified through linkage of the Norwegian MS Registry and the Medical Birth Registry of Norway (1967-2002). All pre MS births (n = 1910), early MS births (n = 555), and manifest MS births (n = 308) were compared.There was a significantly lower mean birth weight in term births (adjusted for gestation in weeks, mother's age, time period and caesarean section) in the manifest MS compared to the pre MS group (P = 0.046). The rate of birth complications and interventions did not differ between the three groups.Manifest MS in birth-giving mothers seems to affect birth weight.     

Analyses of nursing home residents with multiple sclerosis and depression using the Minimum Data Set

Depression is the most common psychiatric condition among people with multiple sclerosis (MS). A total of 14009 people with MS at admission to a nursing facility were analyzed using the Minimum Data Set and 36% also had depression. This study developed profiles of nursing home residents with MS who also had depression and compared them with other residents with MS. MS residents with depression were significantly more likely to be female and younger than other MS residents, with significant racial differences as well. MS residents with depression were significantly more likely than other MS residents to have a history of mental health conditions, exhibit mood indicators, and have unsettled relationships. Both groups of MS residents had high levels of physical disability, although MS residents with depression tended to be slightly less disabled. MS residents with depression were more likely than other MS residents to experience daily pain and more likely to have the diseases common to all residents with MS. This research found that most MS residents with depression did not receive mental health services, demonstrating that nursing facilities must improve the mental healthcare provided to residents with MS with depression.     

An immunogenetic heterogeneity in multiple sclerosis.

Two clinical forms of multiple sclerosis (MS), primarily chronic progressive MS (PCP MS) and relapsing/remitting MS (R/R MS) have been shown to differ in several respects. The results of genomic HLA class II typing with restriction fragment length polymorphism analysis of 62 MS patients from Western Norway, 42 with R/R MS and 20 PCP MS, are reported on here. As in previous studies of Swedish patients, the haplotype DRw17(3), DQw2 was found to be five times more common in R/R MS than in PCP MS. This finding supports the hypothesis that R/R and PCP MS are immunogenetically separate entities. In contrast with a previous investigation of Norwegian MS patients, no association of MS with glutamine at position 34 of the HLA-DQ alpha chain or with defined sequences of the HLA-DQB1 gene was found.     

Recent gains in clinical multiple sclerosis research

Multiple sclerosis (MS) is a common neurological disease mainly affecting young people. Around the world, over 2.5 million people suffer from this central nervous system (CNS) disorder. Although the exact disease mechanism is not completely clear, it is known that both environmental and genetic factors influence the development of MS. Here we aim to summarize a few major highlights of recent progress that have been made in clinical MS research. A genetic predisposition in combination with Epstein-Barr virus infection seems to be essential to get MS. Recently more than 50 susceptibility genetic loci for MS have been described. MS prevalence has a latitudinal gradient indicating that sunlight exposure and therefore vitamin D are important contributors to MS risk. Several studies found an inverse association between MS prevalence and serum vitamin D levels. In most cases, MS starts with an acute episode involving one or more sites of the CNS. The role of the recently revised McDonald Diagnostic Criteria for the diagnosis of MS, which sometimes allow the diagnosis after a first attack, is discussed. Most patients with MS suffer from exacerbations and remissions of neurological deficits: relapsing-and remitting MS. With time, the majority of these patients enter a disease phase characterized by continuous, irreversible neurological decline; this is called secondary progressive MS. In 10-20% of patients, the disease is progressive from onset. Life expectancy of patients after diagnosis with MS is around 35 years, and MS patients die 5-10 years earlier than the general population. A substantial percentage of MS patients have their first attack during childhood. Clinics of childhood-onset MS versus adult-onset are explained, as are diagnostics, differential diagnoses and therapeutic options for children with MS. Also another demyelinating disease of the CNS, neuromyelitis optica (NMO) is highlighted. Since NMO has been considered as a variant of MS and also has been misdiagnosed as MS, recent insights in the pathology of NMO are explained.     

Pediatric multiple sclerosis

The onset of multiple sclerosis (MS) in childhood is being increasingly recognized. Despite this, there currently exist several barriers to the prompt diagnosis of MS in children. Many clinicians view MS as an exclusively adult-onset disease, and thus they may not entertain the diagnosis in a child. Also, the clinical and radiographic criteria for the diagnosis of MS have not been validated in a pediatric MS population. The available literature, as well as experience gained in a dedicated pediatric MS clinic, is used here to describe features of pediatric MS and contrast these with adult MS. The rationale and importance of future studies in pediatric MS is highlighted.     

Quantitation of multiple sclerosis specific central nervous system antigens in various regions of MS brains

We have estimated the levels of partially purified multiple sclerosis (MS) specific glycoproteins (MSG2) in gray matter, white matter, spinal cord and brain stem of MS autopsy brains by an enzyme immunoassay in which antisera to a pooled MSG2 was employed. Similarly, the levels of KG2 (non-MS brain isolate corresponding to MSG2) were assayed in various topographic areas of non-MS autopsy brains. Comparison of data on MS and non-MS groups revealed that the MS specific antigens may be preferentially located in the normal appearing white matter of MS brains. The concentration of MS antigens was found to be highest in the normal appearing white matter of MS brains, followed by periplaque and finally plaque. These results indicate that the MS specific antigens are not the degraded products of MS brains. They further support the view that normal appearing white matter of MS brains should be the target tissue for the isolation of MS specific antigens.     

精神分裂症合并代谢综合征的调查

目的调查精神分裂症合并代谢综合征（metabolic syndrome,MS）的患病率及相关因素。方法对住院的210例精神分裂症患者进行MS调查和相关实验室指标测定,MS的诊断标准采用2004年中华医学会糖尿病分会标准。结果资料完整的精神分裂症住院患者210例;精神分裂症患者合并MS的患病率为18．9％,72．1％的患者至少有1项MS成分;MS组饮酒史阳性者比例显著高于非MS组（P〈0．05）;体重指数（BMI）与MS的发生直线相关（r=0．350,P〈0．01）。结论精神分裂症患者具有较高的MS发生风险,BMI是一项重要的预测指标,饮酒史是危险因素。     

Clinical and magnetic resonance imaging features of multiple sclerosis with autoreactive antibodies in Ishikawa Prefecture, Japan

Previous reports of multiple sclerosis (MS) with autoantibodies might include neuromyelitis optica (NMO). We investigated the frequency of autoreactive antibodies (AR) in both MS and NMO. Systemic lupus erythematosus (SLE)-associated autoantibodies such as anti-Sm antibodies, anti-single stranded DNA antibodies and lupus anticoagulants were only identified in MS, whereas SLE itself is more commonly associated with NMO. Moreover, when magnetic resonance imaging features between autoreactive antibody-positive (AR(+))MS and -negative (AR(-))MS were compared, AR(+)MS cases showed significantly fewer than 3 periventricular lesions compared to AR(-)MS cases. These results may indicate different pathogenetic mechanisms underlying AR(+)MS and AR(-)MS.     

Age at onset of multiple sclerosis may be influenced by place of residence during childhood rather than ancestry

Multiple sclerosis (MS) most commonly affects individuals of Northern European descent who live in countries at high latitude. The relative contributions of ancestry, country of birth and residence as determinants of MS risk have been studied in adult MS, but have not been explored in the pediatric MS population. In this study, we compare the demographics of pediatric- and adult-onset MS patients cared for in Toronto, Ontario, Canada, a multicultural region. The country of birth, residence during childhood, and ancestry were compared for 44 children and 573 adults. Our results demonstrate that although both the pediatric and adult cohorts were essentially born and raised in the same region of Ontario, Canada, children with MS were more likely to report Caribbean, Asian or Middle Eastern ancestry, and were less likely to have European heritage compared with individuals with adult-onset MS. The difference in ancestry between the pediatric and adult MS cohorts can be explained by two hypotheses: (1) individuals raised in a region of high MS prevalence, but whose ancestors originate from regions in which MS is rare, have an earlier age of MS onset, and (2) the place of residence during childhood, irrespective of ancestry, determines lifetime MS risk -- a fact that will be reflected in a change in the demographics of the adult MS cohort in our region as Canadian-raised children of recent immigrants reach the typical age of adult-onset MS.     

Multiple sclerosis and birth order: a longitudinal cohort study

BACKGROUND: Genetic epidemiological studies suggest both genetic and environmental factors have a role in multiple sclerosis (MS). Environmental effects are strongly suggested from geographical gradients, migration data, and discordance rates in twins. In epidemiological studies, risk of MS in offspring of small families and in those with an early birth-order position has been reported and interpreted in the context of the hygiene hypothesis, which is that infections at an early age, introduced by older siblings, are protective. We aimed to study the effect of birth order on MS risk. METHODS: A longitudinal, population-based sample of individuals with MS and their healthy siblings were identified from the Canadian Collaborative Project on Genetic Susceptibility to MS. Data were grouped according to single (simplex) or multiple (multiplex) siblings with MS in a sibship. Separate analyses were done for each sibship size. FINDINGS: We studied 10 995 individuals with MS and 26 336 healthy siblings, and found no relation between MS risk and birth-order position. In simplex sibships of at least seven siblings, slightly more siblings who were born late in the birth order had MS; the same was found for the first-born sibling with MS in a multiplex sibship. Siblings with MS were slightly younger (p<0.0001) than those without MS, contrary to the expected age at onset bias. INTERPRETATION: These findings do not support the hygiene hypothesis and could be due to a cohort effect resulting from increasing MS incidence. Birth order has no effect on MS risk in most families, and there is no support for the hypothesis that having older siblings protects against MS.     

Recent progress in treatment for multiple sclerosis]

Multiple sclerosis (MS) is currently considered to be an autoimmune disease mediated by myelin antigen-specific Th 1 cells. Although the mechanism of MS remains to be elucidated, new disease modifying drugs have recently been introduced to MS treatment. Interferon-beta, copolymer 1 and intravenous administration of immunoglobulins have been shown to significantly reduce the relapse rate, progression of disease and increase of MRI lesion load in MS. However, as the effects of these drugs are nonspecific immunomodulation, specific immunomodulation therapy for MS is called for. T cell vaccination, altered peptide ligand and oral tolerance are possible candidates for specific immune therapy for MS. As in Asians there is such a distinct subtype of MS as HLA-DPB 1 * 0501-associated opticospinal MS, it is important to look for unique immune therapy for opticospinal MS in future.     

Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."     

Innate production of interleukin-10 and tumor necrosis factor affects the risk of multiple sclerosis

Multiple sclerosis (MS) typically presents with a relapsing-remitting onset. This can be distinguished from primary progressive MS. Typical MS is characterized by a profound inflammatory reaction in which anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor (TNF) may play a pivotal role. We tested the hypothesis that patients with MS have a distinct innate cytokine production that contributes to the susceptibility for and outcome of MS. The innate cytokine production of patients was estimated as the average production of cytokines in lipopolysaccharide -stimulated whole-blood cultures of 2 to 5 first-degree healthy family members. A total of 126 family members of 50 patients with typical MS, 61 family members of 25 patients with primary progressive MS, and 129 control subjects of 54 families were enrolled in this study. We found that members of families with low IL-10 and high TNF production had a fourfold increased risk of developing typical MS compared with members of families with high IL-10 and low TNF production. Patients with MS were eightfold more likely to develop typical MS than primary progressive MS when they belonged to families with low IL-10 and high TNF production. The presence of human leukocyte antigen-DR2 was associated with MS but not with TNF production. This study shows that typical MS is associated with an innate pro-inflammatory cytokine profile in contrast to primary progressive MS.     

Nursing home residents with multiple sclerosis and dementia compared to other multiple sclerosis residents

Cognitive impairment may be a significant symptom in multiple sclerosis (MS), affecting about one half of MS patients in study samples similar to the general MS population. An interesting question is what role dementia, of any aetiology, plays in the cognitive ability of people with MS. The objective of this research is to learn more about nursing home residents with MS and dementia, identifying how they differ from other residents with MS. We developed profiles of MS residents with dementia using the Minimum Data Set and compared these profiles to other residents with MS. Nursing home residents with MS and dementia are admitted to nursing facilities at an older age and seem less likely to have physical impairments but more mood and behaviour problems than other MS residents at admission. A cortical variant of MS may be more prevalent than previously suspected and may be a factor responsible leading to nursing home admission in this subgroup of patients. Further clinical analysis of this subgroup would be necessary to support this contention.     

HLA antigens-linked genetic control in multiple sclerosis patients resistant and susceptible to infection

Patients with multiple sclerosis (MS) from the two Montreal MS clinics, were divided into two groups: one group of 61 patients (MS type I) who had no clinical history of susceptibility to recurrent respiratory tract infections and a second group of 58 patients (MS type II) who had persistent susceptibility to such infections since childhood. All patients were typed for the HLA tissue antigens. The HLA antigen frequencies of the total MS patient population, and of MS type I and MS type II patients were compared to those of a normal control population and each other. The HLA-DR2 and B7 antigen frequencies were significantly increased compared to the normal controls for all MS patients. MS type I patients had an increased frequency for HLA-Bw42 and DRw8 antigens; the frequency of HLA-A29 was lower than in the controls and MS type II patients. MS type II patients had a significantly increased frequency for DR3 and some HLA-DR3-associated phenotypes (A1 + DR3; B8 + DR3; A1 + B8 + DR3) as compared to controls and MS type I patients. These results are consistent with the existence of genes linked to the HLA antigens, such as immune response genes, which control the resistance or susceptibility of the patients to infection, and suggest that these HLA antigens could be associated with a difference in the evolution of MS, as observed in the MS type I and II patients [21].     

多发性硬化患者血清及脑脊液中干扰素-γ水平的研究

目的研究多发性硬化患者血清及CSF中干扰素-γ水平的变化,探讨干扰素-γ在MS发病中的作用。方法选择58例河北医科大学第二医院住院MS患者,临床表现符合Poser等制定标准的确诊(definite)或很可能(probable)MS诊断。选择40例无血缘关系的健康人,年龄、性别均与病例组匹配,近期无感染、未应用免疫抑制剂。血液及CSF标本应用双抗体夹心酶联免疫(ELISA)方法测定干扰素-γ含量。结果急性期MS组血清及脑脊液IFN-γ水平较正常对照组及缓解期MS组明显升高,且脑脊液INF-γ增高程度明显。结论 INF-γ水平在MS急性期增高,并随病情的缓解而逐渐恢复正常,说明INF-γ在MS发病过程中起促进作用。     

Depression in multiple sclerosis: a review

Several studies have reported high rates of depression in multiple sclerosis (MS) with a lifetime prevalence of ～50% and an annual prevalence of 20% not uncommon. Concern about the potential of new drug treatments to exacerbate or precipitate depression in MS has led to increased interest in the relation between MS and depression. This review on MS and depression identifies the following key issues: How common is depression in people with MS? Is depression in MS associated with lesions in specific regions of the central nervous system? Is there an increased risk of suicide in MS? Is there a higher than expected incidence of anxiety disorders in MS? Are fatigue and depressed mood related in MS? Is there a relation between depression and cognitive impairment in MS? Which psychosocial variables affect the development of depression in MS? Does treatment with interferon increase the risk of depression? How effective are treatments for MS patients with depression? Each of these issues is briefly reviewed with critical commentary, and some priorities for future research are suggested.     

Assessment Of Depression In Multiple Sclerosis: Development Of A “Trunk And Branch” Model

The objective of the present investigation was to improve the detection of depression in multiple sclerosis (MS). It has been hypothesized that the overlap of MS symptomatology and neurovegetative depression symptoms may lead to an over-diagnosis of depression in MS. Discerning what is depression and what is more attributable to the disease renders a complicated picture when assessing depression in medically ill people. Given this, “trunk and branch” models have been proposed. In such models “trunk” symptoms are purported to be the symptoms common to the medical condition and less likely reflective of depression. “Branch” items are those symptoms that are independent of the medical condition and likely reflect depression. In the present investigation we compared depressed individuals with MS, non-depressed individuals with MS, and non-depressed controls, to devise a “trunk and branch” model for use with individuals with MS. By identifying which symptoms are typical in MS, which exceed what is typical in MS, and which symptoms are independent of MS, but more often present in depressed individuals with MS, we hoped to present a better understanding of the nature of depression in MS.     

Multiple sclerosis in the Japanese population

Multiple sclerosis (MS) in Asian populations is characterised by the selective and severe involvement of the optic nerve and spinal cord as well as low prevalence rates. 15-40% of cases of MS in Japan are of this "opticospinal" type. This form of MS generally has a higher age at onset and a higher female to male ratio than conventional MS. Opticospinal MS is also characterised by frequent relapses, severe disability, few brain lesions visible on MRI, long lesions extending over many vertebral segments visible on spinal-cord MRI, pleocytosis and an absence of oligoclonal bands in the CSF, and a pronounced shift in the responses of T-helper-1 and T-cytotoxic-1 cells throughout relapse and remission phases. Conventional MS in Japanese people is, like MS in white people, associated with HLA-DRB1*1501, whereas opticospinal MS is associated with HLA-DPB1*0501. In Japanese people born after modernisation in the 1960s, the ratio of conventional to opticospinal MS has increased rapidly. Opticospinal MS is likely to have a distinct immune-mediated mechanism, which is not operative in conventional MS.     

诊断多发性硬化的Poser标准与McDonald新标准的比较

目的 比较诊断多发件硬化(multiple sclerosis,MS)的Poser标准和McDonald新标准.方法 将Poser标准和McDonald新标准回顾性应用于临床表现提示为MS的67例患者,采用Fisher精确枪验对两种诊断标准进行比较分析.结果 符合Poser临床和实验室确诊者分别为34例和24例,可能MS者9例,符合McDonald标准的MS确诊者36例,可能MS者31例,两种标准的诊断阳性率差异有统计学意义(OR=5.549,95%CI 2.37～13.00,P<0.01).结论 两种标准住诊断MS,尤其在确诊MS时有明显差异,这可能主要与Poser标准更多地依赖各种亚临床证据,而McDonald标准采用了更为严格的MRI规定有关,脑脊液分析可能在一定程度上有助于提高MS的确诊率和MRI异常的病理特异性.