Pregnancy and multiple sclerosis

Pregnancy is a major concern in multiple sclerosis (MS), because the typical patient is a young woman of childbearing age. This article reviews the impact of pregnancy on MS. Disease activity decreases, particularly during the last trimester. There is a temporary rebound of disease activity in the 3 months postpartum. Pregnancy and the postpartum period have many implications for counseling and for therapeutic decision making in MS.     

The spectrum of multiple sclerosis and treatment decisions

An increasing number of patients referred for neuroimaging studies unrelated to multiple sclerosis (MS) are found to have incidental lesions suggestive of MS in their nervous systems but many such patients do not develop clinical symptoms and signs and remain as "subclinical MS" (SCMS). MRI and cerebrospinal fluid (CSF) studies in monozygotic twins and siblings of MS patients, as well as necropsy studies in asymptomatic persons also reveal findings consistent with SCMS. Clinically isolated syndromes (CIS), acute disseminated encephalomyelitis (ADEM), benign MS, relapsing-remitting MS, primary and secondary progressive MS, optico-spinal MS, Balo's and Marburg's diseases, are considered different forms of MS by many because of their heterogeneous clinical, imaging and pathological features. Studies of disease susceptibility, type, course and severity have given different results in different populations, consistent with "genetic heterogeneity". The various forms of the disease may change from one to another, and their clinical and imaging features became similar after a number of years. The current data support the concept that MS, whether it is a single disease or a group of disorders, is an immune-mediated disease of the CNS, with both inflammatory and degenerative features with available therapies being only partially and temporarily effective for the inflammatory phase of the disease. Making the diagnosis of MS may not be an absolute indication for early treatment with disease modifying agents. The use of new technology such as microarray and other techniques in diagnosing and understanding the MS spectrum may make it possible to recognize the different molecular subtypes of these diseases and develop better therapies.     

Paroxysmal ataxia and dysarthria in multiple sclerosis

Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.     

Treatment of multiple sclerosis exacerbations

The understanding of the mechanisms that lead to MS exacerbations continues to produce novel treatments for patients with relapsing forms of MS. However, even with the most potent agents available, the exacerbations remain a distinct possibility and a source of concern for patients and clinicians. Therefore, the treatment of acute MS exacerbations remains an indispensable element of MS care. Reviewed here are the available treatment options, their implementation, side effects, and evidence supporting their efficacy in promoting recovery from MS relapses.     

Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study

A neurological surveillance was combined with prospective recording of upper respiratory and gastrointestinal infections and serological diagnosis of five common viral infections in 60 benign multiple sclerosis patients, with a mean follow-up of 31 months. During 4-week at risk (AR) periods encompassing common infections, a significant excess of MS relapses was found in the AR period, with a relative risk of 1.3. A seasonal variation of the MS relapse rate was found with a minimum in summer. There was a significant correlation between the number of AR relapses and the number of common infections per month explaining the periannual distribution of relapses. The non-AR relapses showed no seasonal variation. There was a significant correlation between adenovirus CF titre rises associated with upper respiratory infections and the occurrence of a major MS relapse in the AR period (n = 7), while influenza infections were not followed by a major MS relapse (n = 6). Linear homologies have been demonstrated between adenovirus and basic myelin protein. The epidemiological approach is essential to our understanding of systemic antigens triggering multiple sclerosis activity.     

Pregnancy and multiple sclerosis —a 3-year prospective study

A prospective study of the level of disability, severity and distribution of relapses in 15 women with multiple sclerosis prior to, during and up to 3 years following pregnancy was undertaken. The pregnant group was compared with 22 nulliparous women attending the same clinic and matched for age and severity and duration of disease. In the pregnant group, relapses were more frequent and severe than expected values during the first 6 months post partum, but were below expected values 6–24 months post partum. Over the total study period, therefore, there were no significant differences in relapse number, Expanded Disability Status Score or functional scores between the two groups. Babies born during the study showed normal distributions of weight and head circumference.     

Association of an EAAT2 polymorphism with higher glutamate concentration in relapsing multiple sclerosis

Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Here, we have examined if glutamate homeostasis is altered in plasma from MS patients. We initially observed that plasma glutamate levels are elevated in MS patients as compared to control subjects. In addition, we have studied the presence of a polymorphism sited in the promoter of the glutamate transporter EAAT2 whose mutant genotype results in lower transporter expression. We found that the polymorphism is not associated with the risk to develop MS. However, it is associated with higher glutamate plasma levels during the course of a relapse. These findings suggest that glutamate homeostasis is compromised in MS and that carrying this mutation may contribute to this alteration in relapsing MS.     

Choreoathetosis in multiple sclerosis

Extrapyramidal symptoms are extremely rare in multiple sclerosis. We examined a patient with a ten year history of multiple sclerosis, who developed choreoathetoid movements of both upper extremities. To our knowledge this is the second case report of this association.     

Contribution of relapses to disability in multiple sclerosis

The impact of relapses on long-term disability in multiple sclerosis remains unclear; however some evidence suggests that relapses play an important role in determining subsequent prognosis. We report on outcome, prognostic factors for recovery and the contribution of relapses to the accumulation of fixed disability in a large series of patients with documented relapses. Two hundred and seventynine relapses in 182 patients were assessed before, during and after relapse by expanded disability status scale and data analysed to assess degree of recovery. Factors affecting outcome were considered including sex, age and site of relapse. Mean EDSS prior to relapse was 3.73, during relapse 5.18 and post relapse 4.23. Mean interval to post relapse assessment was 127 days post relapse. Mean residual change in EDSS score (pre to post relapse) was 0.50 points. Overall 49.4 % of patients had a residual increase in disability post relapse of at least 0.5 EDSS points and 32.7 % had an increase of at least 1 point. No significant difference was observed in mean residual EDSS for sex, site of relapse or age at relapse or in the proportion of patients with a residual increase in disability of ≥ 1 EDSS point post relapse. 14.4 % of patients had no increase in EDSS score during relapse compared to pre relapse. These results suggest that acute relapses are commonly associated with an objective worsening of disability in the majority of patients with MS and that recovery is incomplete in approximately half and not influenced by gender, age or site of lesion. Therapies which reduce relapse frequency and/or severity might therefore be expected to slow or prevent worsening of disability if initiated prior to the onset of more permanent damage.     

Hypermetabolism in multiple sclerosis patients

Hypermetabolism, which can lead to wasting syndrome, is well recognized in diseases such as AIDS, cancer, rheumatoid arthritis, sepsis and burns. In these conditions proinflammatory cytokines are thought to be essentially involved. In experimental allergic encephalitis (EAE), which is regarded as an animal model of multiple sclerosis (MS), wasting syndrome and elevated levels of cytokines have also been reported. The aim of this study was to investigate whether hypermetabolism does occur in MS patients. After a 3-day standard diet the basal metabolic rate (BMR) was measured by indirect calorimetry in 20 MS patients and 10 healthy controls. Body composition was assessed using an impedance analyser and lean body mass (LBM) was calculated. Other metabolic disturbances and infectious disease were ruled out by clinical examination and various laboratory tests. Tested by analysis of variance (ANOVA), the BMR corrected for LBM was increased by an average of 6% in the patients group (p < 0.05) as compared to the controls. As far as we know this is the first study demonstrating the presence of hypermetabolism in MS.     

Rehabilitation challenges in multiple sclerosis

While current immunomodulating drugs aim to reduce multiple sclerosis (MS) exacerbations and slow disease progression, rehabilitation aims to improve and maintain the functional abilities of patients in the face of disease progression. An increasing number of journal articles are describing the value of the many rehabilitation interventions that can be used throughout the course of the disease, from the initial symptoms to the advanced stages. An integrated team of healthcare professionals is necessary to address a myriad of problems to reduce impairments, disabilities, and handicaps. The problems may be related to fatigue, weakness, spasticity, mobility, balance, pain, cognition, mood, relationships, bowel, bladder, sexual function, swallowing, speech, transportation, employment, recreation, and activities of daily living (ADL) such as dressing, eating, bathing, and household chores. The team can help prevent complications and secondary disabilities, while increasing patient safety. Improving neurologically related function, maintaining good relationships, and feeling productive and creative adds enormously to the quality of life of people with MS and their families. Rehabilitation is more than an ‘extra’ service that is given after medical therapies; it is an integral part of the management of the diverse set of problems encountered throughout the course of the disease. An interdisciplinary team may have many members, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, psychotherapists, social workers, recreational therapists, vocational rehabilitation therapists, patients, families, and other caregivers.     

Varicella-zoster virus at relapses of multiple sclerosis

Abstract The possible participation of different herpes viruses was studied during exacerbations of multiple sclerosis (MS). We searched for the presence of DNA from the following herpes viruses: varicella zoster virus (VZV), herpes-simplex viruses 1 and 2; Epstein-Barr virus (EBV) and human herpes-virus-6 (HHV6) in mononuclear cells from patients with MS during relapse (n = 40), MS during remission (n = 131) and controls (n = 125). Additionally, immune cells containing viral antigens were quantified by flow cytometry, and VZV load was determined by real time PCR in 2 MS patients at various times during relapse and remission. DNA from VZV was found in 95% of MS patients during relapse and in 17% during remission; all controls were negative; by contrast, DNA from HHV6 was found in 24% of MS patients during relapse and in 2% during remission; DNA from herpes simplex viruses was not found in any subject; and DNA from EBV was found in a similar percentage of subjects from all groups. Sequential quantification of VZV-load showed a curve that increased during relapse and disappeared at remission. Also, VZV antigens were found inside a large number of immune cells from MS patients during relapse as compared with MS patients on remission and controls. In the typical forms of VZV infection, varicella and herpes-zoster, DNA from VZV is found in mononuclear cells exclusively during brief periods at the beginning of the active infection, but not during latency; thus, the conspicuous presence of VZV during relapses of MS may indicate a period of active infection and suggests the participation of VZV in the pathogenesis of MS.     

Western and Asian features of multiple sclerosis in Mexican Mestizos

OBJECTIVES: The objective of this study was to compare the clinical expression of MS in Mexican Mestizos with that of patients of European or Asian descent; as well as to compare the annual frequency of new cases with that observed in the previous decades. PATIENTS AND METHODS: All patients with diagnosis of definite MS seen at the National Institute of Neurology and Neurosurgery of Mexico from January 1993 to December 2003 were studied (n=312). Sociodemographic and clinical characteristics were compared with reports of patients from either Western or Asian origin; the long-term disability score was analyzed according to gender, age of onset of MS and the initial symptom. RESULTS: The clinical expression of MS in Mexican Mestizos shares some characteristics with both, Asian and Western forms of MS indicating that the genetic composition of Mexican Mestizos participates in the clinical expression of the disease. Also, at the prevalence date, the mean age of patients and the duration of the disease were lower in our patients than in MS patients from endemic countries suggesting a true increasing incidence in recent times, rather than only improved case ascertainment. CONCLUSIONS: Clinical expression of MS in Mexican Mestizos shows the coexistence of some features common in European and in Asian cases.     

晚发型多发性硬化

本文报告１５例晚发型多发性硬化（ＭＳ），首次发病年龄５０－６０岁，占同期住院ＭＳ患者的６．４％。通过对其临床表现、病变部位和预后等与同期成人ＭＳ对照分析，表现晚发型ＭＳ慢性起病多见，临床表现和受累部位与成人ＭＳ相似，但脊髓受累较成人ＭＳ更为常见，晚发型ＭＳ大多病情进展快，运动功能障碍严重，病情多不能彻底缓解，预后差。     

Trauma and multiple sclerosis

Summary An obligatory event in the pathogenesis of the multiple sclerosis plaque appears to be an increase in the permeability of the blood-brain barrier. Neuropathological observations of the brain of persons suffering from concussion after relatively minor head injury, as well as of animals subjected to experimental brain injury, have shown that alterations of the blood-brain barrier constitute a common result of such trauma. It is postulated that the alterations of the blood-brain barrier secondary to trauma of the brain or spinal cord of patients with already established multiple sclerosis may result in an exacerbation or recurrence of a previously symptomatic plaque, in the appearance of symptoms from a silent lesion, or in the formation of a new plaque in such an area of selected vulnerability. In other persons injury to the nervous system may cause the development of multiple sclerosis plaques in the previously damaged areas when the disease has its onset after the trauma. There is no evidence to support the idea that trauma ever causes multiple sclerosis.     

The frequency of relapse in multiple sclerosis

Summary The authors analyze the course of 245 cased of multiple sclerosis. The mean annual frequency of attacks is 0.66 for all the patients (remittent forms and progressive forms). Although it is usually suggested that this frequency decreases with the years, this has not been found in our study. Our results also indicate that we would have to follow 590 patients over 1 year or 190 over 2 years before being able to attest the effectiveness of a treatment decreasing the frequency of attacks by 25%.Ingénieur I.N.S.E.R.M.     

Viral antibodies in multiple sclerosis

The sera of 176 MS patients and of 150 healthy adult controls were assayed for antibodies against mumps, rubella, Sendai and herpes simplex viruses, a higher prevalence of measles c.f.a. having already been demonstrated in the MS patients. The CSF of 48 of the MS patients were subjected to the same tests. The patients differed from the controls in a higher prevalence of h.i.a. to mumps and of c.f.a. to herpes simplex. For the latter, but not for the former, the prevalence was statistically higher only in patients treated with immunosuppressants. To date measles seems to be the most seriously incriminated virus in the etiopathogenesis of MS, mumps ranking second.

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Sommario Sono riportiti i risultati delle titolazioni anticorporali verso i virus della parotite, della rosolia, Sendai ed herpes simplex nel siero di 176 pazienti affetti da Sclerosi Multipla e di 150 soggetti sani di controllo, nonché nel liquor di 48 dei malati. In precedenza negli stessi gruppi di soggetti erano stati studiati gli anticorpi antimorbillo. Differenze tra i malati ed i controlli sono state riscontrate solo per la prevalenza nel siero degli anticorpi inibenti l'emoagglutinazione antiparotite e degli anticorpi fissanti il complemento verso l'herpes simplex. Va sottolineato che, al contrario di quanto si è verificato per il virus della parotite, solo i pazienti sottoposti a terapia con farmaci immunodepressivi presentavano una prevalenza degli anticorpi fissanti il complemento verso l'herpes simplex statisticamente maggiore dei controlli. Sulla base delle presenti e di precedenti osservazioni, sembra che il morbillo in primo luogo e la parotite siano i virus per i quali esistono maggiori evidenze di un coinvolgimento nell'eziopatogenesi della Sclerosi Multipla.

     

多发性硬化的MRI特征

目的 探讨多发性硬化(MS)患者脑及脊髓的MRI特征.方法 回顾性分析110例临床确诊的MS患者的MRI检查资料.结果 MS患者脑部病灶以侧脑室旁白质多见(55.8%),其次是额叶深部白质(54.7%)、顶叶深部白质(44.2%)、脑干(25.6%)、基底节(23.3%)、丘脑(11.6%)等,灰质也可受累;病灶大小不一,形态可为斑片状、斑点状、圆形、类圆形.脊髓病灶以颈、胸髓多见,分别占75.0%和68.8%,形态可为斑片状、条片状、类圆形,脊髓灰白质可同时受累,10.0%的患者出现脊髓形态改变,如增粗、萎缩.MS患者脑及脊髓内病灶在影像学上因病程不同可表现为长T1、长T2或等T1、长T2信号.结论 MS的MRI特点主要是以脑和脊髓白质出现多个大小、形状不同的病灶.     

Electrical sensation during Tai-Chi practice as the first manifestation of multiple sclerosis

We report a patient with a 3-year history of brief episodes of electrical sensations over her back and upper limbs that occurred during Tai-Chi practicing. This appearance of Lhermitte's sign was later followed by additional neurologic symptoms, and the patient was diagnosed as sufferring from multiple sclerosis. Though the patient related the Lhermitte's sign to her ability to achieve full relaxation in Tai-Chi exercises, we think it was the first manifestation of the disease.