Epilepsy and multiple sclerosis in Sicily: a population-based study

PURPOSE: To evaluate the association between epilepsy and multiple sclerosis (MS), we analyzed the incidence of epilepsy in a population-based incidence cohort of MS in Catania, Sicily. METHODS: According to Poser's diagnostic criteria, 170 incident cases of MS have been identified from 1975 to 1994 in the city of Catania. All these subjects underwent a complete neurological examination to confirm the diagnosis of MS and to identify those patients with a history of seizures. Diagnosis of epilepsy was based on the criteria proposed by the International League Against Epilepsy (ILAE) in 1993, and seizures were classified according to the classification of the ILAE, 1981. RESULTS: From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence of MS was 2.3/100,000 (95% CI, 2.0-2.6). Of the 170 defined MS patients, four developed epilepsy after the onset and also diagnosis of MS, giving an incidence rate of epilepsy of 285/100,000 person years at risk (95% CI, 119-684) and 147.8/100,000 when age adjusted to the world standard population. The cumulative risk of developing epilepsy after the onset of MS, evaluated by using the life-table methods, was zero at 1 year and 1.76% at 5 years. Of these four patients, three were classified as having partial seizures with secondary generalization and one with tonic-clonic seizures. CONCLUSIONS: Our data are consistent with those reported in literature suggesting that the risk of developing epilepsy is threefold higher among MS patients than in the general population.     

A prospective study of the incidence, prevalence and mortality of multiple sclerosis in Leeds

Objective: To establish the prospective incidence of multiple sclerosis and mortality rates of people with multiple sclerosis in Leeds Health Authority and an updated prevalence of multiple sclerosis on 31 October 1999. Methods A population based prevalence register established on 30 April 1996 was maintained by prospectively registering all new cases of multiple sclerosis, flagging all cases with the National Health Service Central Register for notification of deaths and by registering all new clinical events. General practitioners notified patients with multiple sclerosis moving into or out of the area. Results 136 incident cases were prospectively registered from 30 April 1996 living in Leeds Health Authority (with an estimated resident population of 728 840). 57 deaths were notified. 792 people with multiple sclerosis were identified living in Leeds on 31 October 1999. The mean annual incidence rate for the three-year period 1996–1998 was 6.1/10⁵ (95 % CI: 5.1–7.2). The sex ratio of incident cases was 2.3 to 1 women to men. On 31 October 1999 the prevalence of multiple sclerosis in the Leeds Health Authority was 108.7/10⁵ (95 % CI: 101.2–116.5). This compares with a prevalence of 97.3/10⁵ (95 % CI: 90.3 –104.7) on 30 April 1996. The prevalence of definite and probable multiple sclerosis was 93.3/10⁵ (95 % CI: 86.4–100.6) and of suspected multiple sclerosis was 15.4/10⁵ (95 % CI 12.7 –18.5). Crude annual mortality rates of people with multiple sclerosis for 1997 and 1998 were 1.9/10⁵ (95 % CI: 1.1 to 3.2) and 3.2/10⁵ (95 % CI: 2.0 to 4.7). Multiple sclerosis was noted as the underlying cause of death in 8 (14 %) cases. Conclusion The incidence of multiple sclerosis in the Leeds Health Authority is similar to that in the south of the United Kingdom. The difference in successive prevalence figures is less than that published in other serial studies. Multiple sclerosis was notified as the underlying cause of death in a minority of deaths in people with multiple sclerosis. Received: 5 December 2000, Received in revised form: 23 March 2001, Accepted: 10 July 2001     

The influence of ethnicity on the characteristics of multiple sclerosis: A local population study between Persians and Arabs

Background

Based on previous studies, Iran is located in a low risk area in terms of multiple sclerosis (MS). The objective of this study was to determine and compare the incidence, prevalence and demographic characteristics of MS in two ethnic groups of Persian and Arab over the period spanning 2009 in the Khuzestan province, in the Southwest of Iran.

Methods

A cross-sectional case register study was conducted between January and August 2009. All cases in the region whom were referred to the MS society in the city of Ahwaz were participants in the study. The population data from the Iranian Bureau of Statistics were used to calculate the population at risk based on the 1996 and 2006 census data.

Results

A total of 696 patients were identified according to the McDonald criteria during the last 12 years of which 569 patients were Persian. In 2009 the total prevalence and incidence rates of MS were 16.28 and 2.20 per 100,000 individuals. Based on these values, the female to male ratios were 3.11. The Persians manifested more sensory signs and symptoms (40.2%) but motor deficits (19.1%) and cerebellar findings (18.2%) were seen as being more manifest in Arab individuals. The main difference was observed in the progressive types of MS in which 24.7% of the Arab patients showed progressive type symptoms as compared to 15.9% of the cases in the Persian population.

Conclusion

According to this study the authors conclude that the prevalence and incidence of MS were higher in Persians; however progressive forms of MS with motor and cerebellar signs are more frequent in the Arab ethnic group.     

Epidemiology of multiple sclerosis in Sicily

From epidemiological data obtained over more than 20 years by surveys conducted in different parts of Sicily, it is evident that Sicily is a high-risk area for multiple sclerosis (MS). This is in sharp contrast with the gradient hypothesis. High frequencies have been found in different parts of the island having different geoclimatic features, but at least two cities (Monreale and Enna) had had a prolonged Norman domination. This is in agreement with the hypothesis that MS originated in Northern Europe and spread around the world throughout the raids of the northern peoples. The increase in frequency estimated by follow-up and incidence studies is well established and is only in part linked to the improvement in diagnostic techniques. Finally, it is noteworthy that in the islands of Malta, a few sea miles away from Sicily, the MS prevalence rates are in the range of 4–8 cases per 100 000 persons. This occurrence represents a natural model to investigate MS etiology through analytic studies and genetic analyses.     

视神经脊髓炎和多发性硬化患者颈髓扩散张量成像研究

目的通过扩散张量成像(DTI)比较视神经脊髓炎和多发性硬化患者与正常对照者常规MRI表现正常脊髓的扩散性差异,并探讨其临床应用价值。方法采用平面回波成像技术对10例视神经脊髓炎、14例多发性硬化患者和13例正常对照者进行颈髓DTI检查,分别测量颈椎C2~5水平前索、侧索、后索和灰质兴趣区的部分各向异性(FA)和平均扩散率(MD)。结果与正常对照组相比,视神经脊髓炎组患者前索、侧索、后索FA值降低(均P0.05),左侧侧索、后索、灰质MD值升高(均P≤0.05);多发性硬化组患者右侧侧索、后索FA值降低(均P0.05)。与多发性硬化患者相比,视神经脊髓炎患者侧索FA值更低,左侧侧索和右侧后索MD值更高(均P0.05)。结论 DTI可以检出视神经脊髓炎和多发性硬化患者常规MRI表现正常脊髓的水分子扩散异常,进而发现二者脊髓扩散指标的差异性,为早期诊断与鉴别诊断提供重要信息。     

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.     

Genetics for understanding and predicting clinical progression in multiple sclerosis

Introduction

Multiple sclerosis (MS) is a dys-immune disease of the central nervous system with highly variable and unpredictable long-term outcome.

State of the art

In the early 1970s association between HLA alleles and MS was established. Very recently, the power of Genome Wide Association Studies (GWAS) enabled the identification of several loci involved in immune functions as genetic risk factors in MS. Recent data suggest that common genetic variations might modulate the clinical phenotype of MS through a regulation of key pathophysiological pathways.

Perspectives

Identification of modifier genes might offer an opportunity to explore new relevant therapeutic targets and early prognostic markers. To date, studies of modifier genes in MS are numerous but results are still unclear. This research field may now benefit from large cohorts of patients available for association studies.

Conclusion

In this context, we propose a review of epidemiological and association studies of genetic modifying effect in MS.     

Epidemiology of multiple sclerosis

Multiple sclerosis (MS) is the most common disease of the central nervous system that causes permanent disability in young adults. Based on strong circumstantial evidence, MS is considered to be putative autoimmune disorder, but much remains to be understood about the etiology and clinical onset of the disease. It seems unlikely that MS results from a single causative event, but rather is the result of genetic and environmental factors and the interactions thereof. This article discusses the epidemiology of MS.     

Immunogenetic heterogeneity of multiple sclerosis in Sardinia

Multiple sclerosis (MS) predisposition is thought to be influenced by a complex, yet unclear interaction of genetic and environmental factors. Studying ethnically selected populations may reduce genetic and environmental heterogeneities and help clarify the underlying mechanisms of MS susceptibility. Sardinians kept a homogeneous genetic structure and have among the highest MS frequency rates worldwide. Interestingly, MS in Sardinia is linked to otherwise rare HLA alleles. In this light, recent findings from epidemiological and immunogenetic studies of Sardinian MS are presented. Results confirm that, likely due to significant genetic differences at a microgeographic level, even in this homogeneous population MS is immunogenetically heterogeneous and tends to preferentially cluster in some more archaic areas of the island.     

The prevalence of multiple sclerosis in the world: an update

The systematic study of multiple sclerosis (MS) in populations, started in 1929 by Sydney Allison, now consists of over 400 publications dealing with the prevalence of MS throughout the world. However, any attempt to redefine the pattern of geographical differences in MS frequency remains as difficult as ever. The comparison of prevalence studies carried out in different areas and times is made difficult by the variability in surveyed population sizes, age structures, ethnic origins and composition, and the difficult quantification of numerators, especially regarding the recognition of benign and very early cases. Additionally, complete case ascertainment depends on access to medical care, local medical expertise, number of neurologists, accessibility and availability of new diagnostic procedures, the degree of public awareness about MS, and the investigators' zeal and resources. Critical examination of the more recent data on MS prevalence leads to some revisions of previously held concepts, the most interesting of which is the appreciation of the greater influence of genetic factors on disease acquisition. The rarity of MS among Samis, Turkmen, Uzbeks, Kazakhs, Kyrgyzis, native Siberians, North and South Amerindians, Chinese, Japanese, African blacks and New Zealand Maoris, as well as the high risk among Sardinians, Parsis and Palestinians, clearly indicate that the different susceptibilities of distinct racial and ethnic groups are an important determinant of the uneven geographic distribution of the disease. The updated distribution of MS in Europe, showing many exceptions to the previously described north-south gradient, requires more explanation than simply a prevalence-latitude relationship. Prevalence data imply that racial and ethnic differences are important in influencing the worldwide distribution of MS and that its geography must be interpreted in terms of the probable discontinuous distribution of genetic susceptibility alleles, which can however be modified by environment. Because the environmental and genetic determinants of geographic gradients are by no means mutually exclusive, the race versus place controversy is, to some extent, a useless and sterile debate.     

Two populations with multiple sclerosis

Summary Cross-sectional data from 1,793 cases of definite or probable multiple sclerosis (MS) identified in an extensive population survey in King and Pierce (K-P) Counties, Washington and Los Angeles (LA) County, California, were analyzed. Compared to the U.S. population as a whole, patients were more likely to be divorced and to have more years of schooling. The prevalence of MS was higher for females, and for northern-born, regardless of sex. Reconstructed age-, sex-specific incidence rate estimates for natives of the two areas showed a much higher peak annual incidence occurring in an older age group in K-P than in LA. Earliest symptoms in both areas were numbness in the legs, double vision, and loss of vision in one or both eyes. Weakness in arms, speech difficulties, and urinary incontinence tended to be late symptoms. The overall assessment of disability levels showed more than half of the patients to be fully ambulatory at the time of the first interview, with a somewhat higher proportion of each sex severely disabled in California. The ages of onset tended to be younger in LA than in K-P. The earlier onset of disease and the higher proportion of patients with high disability in Los Angeles County suggest that the course of disease is more malignant in this low-prevalence area.Supported by Grant 2R01 NS 10186 from the National Institute of Neurologic and Communicative Disorders and Stroke, National Institutes of Health. Computing assistance was obtained from the Hospital Data Processing Facility, University of California, Los Angeles (UCLA)     

A double blind study on azathioprine efficacy in multiple sclerosis: final report

Forty patients, affected by multiple sclerosis with remitting-relapsing or progressive course, were included in a double blind study of treatment with azathioprine (2 mg/kg/day) lasting 3 years. The mean changes on the Expanded Disability Status Scale and in the survival analysis show a trend in favour of azathioprine both in slowing disease progression and reducing relapse frequency. These findings, repeatedly observed in similar trials, indicate that azathioprine should be used in the treatment of multiple sclerosis.     

Risk factors of multiple sclerosis: a case-control study

Abstract. We assessed the risk of multiple sclerosis (MS) associated with a series of putative risk factors. We studied 140 patients (90 women) with MS (mean age, 42.1 years; SD=10.2 years; disease duration, 10.9 years, SD=7.5 years) and 131 sexand age-matched controls. Using a structured questionnaire, we collected information related to demographic data, socio-economic status, education, ethnicity, changes of domiciles, migration, occupation, environmental, nutritional and hormonal factors, exposure to various bacterial and viral agents, vaccinations, and family history of diseases. In multiple logistic regression analysis, we found independent risk factors of MS to be: familiarity for MS (OR=12.1; 95% CI, 1.3–110.7), autoimmune diseases (OR=3.8; 95% CI, 2.0–7.1) and migraine (OR=8.7; 95% CI, 1.0–75.4); comorbidity with autoimmune disease (OR=6.8; 95% CI, 1.4–32.0) and migraine (OR=13.5; 95% CI, 1.5–116.6); and vaccination against measles (OR=92.2; 95%, 12.1–700.2). Familial susceptibility to MS, autoimmune diseases and migraine, and vaccination to measles are associated with an increased risk of MS. The data collected in this study are confirmatory and support the hypothesis that etiology of MS constitutes the effect of interplay between genetic and environmental risk factors. However, the relatively small number of cases and controls prevents firm conclusions.     

Prevalence and clinical features of multiple sclerosis in Latin America

Multiple sclerosis (MS) in Latin America (LA) is considered to have a low to medium prevalence. However, accurate information on MS in LA is scarce. The aim of this study was to compare clinical characteristics among LA patients through a systematic review of the literature. A systematic search (Spanish, Portuguese and English) was done for all clinical studies of MS in humans (MEDLINE, PubMed, Scielo, BIREME, EMBASE and LILACS) up to May 2011 being focused on a well-defined Latin American population (peer-reviewed journal) following the MOOSE guidelines. The search strategy included combinations of different Mesh terms (two independent researchers). Classification of each article by using the Oxford Centre for Evidence-based Medicine – Levels of Evidence was done. The total number of patients per country for each specific characteristic was compiled. Chi-square test was used to compare the characteristics in the studies retrieved per country. There were 38 articles fulfilling the inclusion criteria, accounting for 4524 patients. Relapsing-remitting form was the most frequent in LA patients and the main initial symptom was motor, followed by optic neuritis and sensorial. A mild expanded disability status scale was the most prevalent in all LA countries. Factors accounting for differences in distribution and clinical course across LA countries include genetics, environment, diagnostic techniques, socioeconomic structure and medical facilities.     

多发性硬化患者头颅磁共振、诱发电位和IgG指数的对比研究

报道43例多发性硬化(MS)患者头颅磁共振成像(MRI)、诱发电位(EP)和IgG指数(IgGIndex)的对比研究结果。发现MRI的检测异常率为81.4％,而VEP仅53.7％、BAEP47.5％、IgGIndex57.5％。MRI在显示空间脱髓鞘方面是最敏感的方法,但VEP、BAEP只要有一项异常即判断为EP异常则其异常率高达79.5％,接近MRI。作者认为三者同时检查可以提高诊断的准确性。     

Prevalence and pattern of multiple sclerosis in Benghazi, north-eastern Libya

A search for Libyan patients with multiple sclerosis (MS) was made in Benghazi, located on the southern Mediterranean coast at a latitude of 32 degrees N. Twenty-one clinically definite and probable cases were detected during the period July 1982-June 1984. On the basis of 2 probable incidental cases, the incidence for 1983 was 0.8 per 100 000 of the population at risk (10-50 years). On July 1st, 1984, the rough prevalence rate for the total population was 4 per 100 000 and the age-adjusted prevalence rate was 5.9 per 100 000. This study suggests that Benghazi falls within the medium frequency band for MS. High prevalence of brainstem involvement and cerebellar dysfunction and infrequent occurrence of the severe optic-spinal form and sphincter disturbance indicates that the present group of patients resembles Western pattern of MS as opposed to Asian MS.     

Optic neuritis in relation to multiple sclerosis

Summary Available estimates of the frequency with which a patient with optic neuritis develops multiple sclerosis range from as low as 13 percent to as high as 87 percent. In an effort to obtain a better estimate, a nation-wide study of optic neuritis was carried out in Israel. Patients who fulfilled strict diagnostic criteria of optic neuritis were identified and examined periodically.Between 1955 and 1964, 105 patients were found and on the basis of these, the average annual age-adjusted incidence of optic neuritis in Israel was 0.56 per 10⁵ population compared to 1.2 per 10⁵ cases of multiple sclerosis per year, i.e. optic neuritis was about half as frequent as multiple sclerosis each year. As with multiple sclerosis, optic neuritis was more common in European immigrants to Israel than in Afro-Asian immigrants.During a follow-up interval which ranged from 3.3 to 15.6 years (mean 9.5 years), at least 27 of the 105 patients developed multiple sclerosis (28 percent). A life-table analysis showed that after 10 years 32.3 ± 5.6 percent of patients with optic neuritis would develop multiple sclerosis and, after 14 years, about half would develop multiple sclerosis.Risk of dissemination was highest in those who were youngest when optic neuritis developed. Neither sex nor ethnic background influenced risk significantly. Results of the present study support earlier work using life-table methods carried out in Hawaii which also showed that between 29 and 39 percent of patients with optic neuritis will develop multiple sclerosis within 10 years of onset. The life-table method is a better predictor of prognosis than newer laboratory techniques such as spinal fluid studies of IgG, kappa-lambda light chain ratios and serum/CSF IgG ratios.

---

Zusammenfassung Schätzungen der Häufigkeit, mit der ein Patient mit Retrobulbärneuritis eine Multiple Sklerose bekommt, schwanken zwischen 13 und 87%. Um zu genaueren Werten zu kommen, wurde eine die ganze Bevölkerung umfassende Studie in Israel ausgeführt. Patienten mit den typischen Merkmalen einer Retrobulbärneuritis wurden erfaßt und periodisch untersucht.Zwischen 1955 und 1964 wurden 105 Patienten gefunden. Das ist eine durchschnittliche jährliche altersbereinigte Häufigkeit der Retrobulbärneuritis in Israel von 0,56 bei einer Bevölkerungszahl um 10⁵. Verglichen damit ist die jährliche Häufigkeit der Multiplen Sklerose 1,2 auf 10⁵, d. h. die Retrobulbärneuritis ist halb so häufig wie die MS. Wie die MS ist die Retrobulbärneuritis häufiger in Israel unter europäischen Einwanderern als bei Afro-Asiaten.Während der Kontrollperiode von 3,3 bis 15,6 Jahren (Durchschnitt 9,5 Jahre) zeigte sich bei 27 der 105 Patienten eine MS (28%). Die Sterbetafeln ergaben eine Häufigkeit von 32,3 ± 5,6% nach 10 Jahren, nach 14 Jahren zeigte sich etwa bei der Hälfte der Patienten eine MS. Das Risiko war am höchsten bei den jüngsten Patienten. Weder Geschlecht noch ethnische Abstammung beeinflußten dieses Risiko signifikant.Die Ergebnisse der Studie bestätigten frühere Untersuchungen in Hawaii, die nach den Sterbetafeln eine Häufigkeit von 29 bis 39% ergab, mit welcher innerhalb von 10 Jahren nach Ausbruch der Retrobulbärneuritis eine MS auftrat. Die Sterbetafeln gestatten eine bessere Voraussage der Prognose als neuere Labortechniken wie die Untersuchung der IgG im Liquor, der Kappa-Lambda leichte Kettenrationen und IgG in Serum und Liquor.

     

The epidemiology of multiple sclerosis in Queensland, Australia

An epidemiological survey of multiple sclerosis (MS) in the State of Queensland was undertaken with its prevalence day being the national census day on June 30th, 1981, 20 years after a regional survey within the State. The relationship between increasing prevalence of MS and increasing south latitude within the State of Queensland which was suggested by the 1961 study was confirmed in the present study. The prevalence rate had increased significantly over the 20-year period between the studies but the State remained a medium frequency zone for MS (prevalence rate between 5 and 29 per 100 000 of population). Although a real increase in disease frequency could not be excluded as a contributing factor to the rise in prevalence, it was most likely due predominantly to an increase in life expectancy amongst the MS population and also in differential migration of a population at a greater risk of developing MS than the indigenous population. The proportions of Australian-born patients who had migrated to Queensland from the higher risk southern regions of Australia or travelled overseas to countries known to be high-risk for MS prior to disease onset, had fallen between the two surveys thus exerting, if anything, a negative influence on the change in prevalence. Analysis of MS prevalence rates amongst migrant populations in Queensland as compared to the more southerly city of Perth in Western Australia, suggested that the risk of acquisition of MS may extend over a wider age range than is generally accepted. Finally, there was an absence of MS cases amongst the Aboriginal population in Queensland but it can only cautiously be concluded from this study that the disease is rare in these peoples.     

Incidence of multiple sclerosis in Bagheria City, Sicily, Italy

We investigated the incidence of multiple sclerosis (MS) in a Sicilian community located a sea level. The study was a retrospective search for MS patients. Incidence was studied in the period from 1 January 1985 to 31 December 1994. We searched for definite MS patients, according to Poser's criteria, among the population resident in Bagheria (Palermo province). There were 25 subjects affected by MS, of which 20 were incident MS patients. The average annual incidence was 4.4 per 100 000 persons (n = 453 385 person-years). The incidence increased over time (1985–1989 = 3.5, 1990–1994 = 5.3). A parallel decrease of the interval between onset and diagnosis of MS was observed (1985–1989, 3.7 years, 95% CI = 1.6–7.3; 1990–1994, 1.9 years, 95% CI = 1.0–3.3). These results confirm that MS is frequent in Sicily. Received: 19 October 2000 / Accepted in revised form: 18 December 2000     

Sexual dysfunction in multiple sclerosis: a MRI,neurophysiological and urodynamic study

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T₁ and T₂ lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C₂ level. Spearman's rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p<0.0001), cognitive performances (r=−0.63, p<0.0001), level of independence (r=−0.63, p<0.0001), disability (r=0.56, p<0.001), symptoms of anxiety (r=0.55, p<0.001) and depression (r=0.50, p<0.005), disease duration (r=0.42, p<0.02) and parenchymal atrophy in the pons (r=−0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T₁ lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.