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.     

Psychotic onset of multiple sclerosis

A case is reported of a woman in whom acute manic attacks were followed later in life by neurological signs of multiple sclerosis, thus suggesting a possible correlation between the two clinical entities.

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Sommario è descritto il caso di una donna in cui la sclerosi multipla fu preceduta da attacchi acuti di tipo psicotico (maniacale).

     

HLA-antigens and the prognosis of multiple sclerosis

Summary The histocompatibility pattern of 160 patients with multiple sclerosis (MS) living in the epidemiological area of Southern Lower Saxony was determined and compared to a control population. The only significant difference was the more frequent occurrence of DW2 in the patient group (44% vs. 21%). Taking a progression index (grade of disability divided by the duration of the disease) as a measure for prognosis no difference could be found between the DW2 positive and the DW2 negative patients. The reason why we could not confirm the worse prognosis for DW2 positive patients found by Jersild et al. (1973) and Raun et al. (1980) remains to be investigated.This work was supported by the Deutsche Forschungsgemeinschaft in the frame of the Schwerpunktprogramm: Etiology and Pathogenesis of Multiple Sclerosis and Related Diseases     

Physiopathology and treatment of fatigue in multiple sclerosis

Fatigue is a common symptom of patients with multiple sclerosis (MS). It is reported by about one-third of patients, and for many fatigue is the most disabling symptom. Fatigue may be associated with motor disturbances and/or mood disorders, which makes it very difficult to determine whether the fatigue is an aspect of these features or a result per se of the disease. Although peripheral mechanisms have some role in the pathogenesis of fatigue, in MS there are clear indications that the more important role is played by “central” abnormalities. Neurophysiological studies have shown that fatigue does not depend on involvement of the pyramidal tracts and implicate impairment of volitional drive of the descending motor pathways as a physiopathological mechanism. Metabolic abnormalities of the frontal cortex and basal ganglia revealed by positronemission tomography and correlations between fatigue and magnetic resonance imaging lesion burden support this hypothesis. Some recent studies also suggest that pro-inflammatory cytokines contribute to the sense of tiredness. No specific treatments are available. Management strategies include medications, exercise, and behavioural therapy; in most cases a combined approach is appropritate. Received: 26 September 2000, Accepted: 28 September 2000     

多发性硬化交感神经皮肤反应的研究

对３８例多发性硬化（ＭＳ）患者和４１例正常人的交感神经皮肤反应（ＳＳＲ）与多方式诱发电位进行研究。结果：３８例确诊和近似确诊的ＭＳ患者ＳＳＲ异常率（８１．６％）比异常的诱发电位更为常见。在伴有自主神经症状的２１例ＭＳ患者中１９例ＳＳＲ异常（９０．５％），１７例无自主神经症状的ＭＳ患者中１２例ＳＳＲ异常（７０．６％）。提示：ＳＳＲ能客观有效地反映自主神经功能状态，检出ＭＳ的亚临床异常。将ＳＳＲ与多方式诱发电位联合评估ＭＳ中枢神经系统损害，具有更高的敏感性，有助于ＭＳ的早期诊断。     

Contribution to the histoenzymatic changes in multiple sclerosis

Summary The activities of acP, alkP, ATP-ase, TPP-ase, non-specific esterase, ASS, AChE and ChE have been investigated by histochemical methods, in the brain of 2 cases of multiple sclerosis.A decrease in the activity of ASS, AChE, ChE and alkP was noticed in the demyelinated white matter of the plaques. Inside the plaques also a loss of ChE activity in the oligodendroglia was observed, whereas the activity of ATP-ase, TPP-ase and acP was increased.The significance of the changes found of the neuroglia hyperactivity in demyelination is discussed.

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Zusammenfassung Histochemische Untersuchungen der Aktivität der sauren und alkalischen Phosphatase, der ATP-ase, der TPP-ase, der unspezifischen Esterase, der Arylsulfatase, der Acetylcholinesterase und der Cholinesterase im Gehirn von 2 Multiple Sklerosefällen. Die Aktivität der Arylsulfatase, der Acetylcholinesterase, der Cholinesterase und der alkalischen Phosphatase verschwindet in den Entmarkungsherden beinahe vollkommen. Im Bereich der Entmarkungsherde war die Cholinesteraseaktivität der Oligodendrogliazellen völlig gewichen, während die Aktivität der ATP-ase, TPP-ase und der sauren Phosphatase erhöht erschien. Die Bedeutung der festgestellten Hyperaktivität der Neurogliazellen in den Entmarkungsprozessen wird diskutiert.

     

The diagnosis of multiple sclerosis and the clinical subtypes

The diagnosis of multiple sclerosis (MS) requires objective findings referable to the central nervous system. A wide differential diagnosis often has to be considered. Magnetic resonance imaging and electrophysiologic and cerebrospinal fluid studies can all contribute to an early definitive diagnosis. The McDonald diagnostic criteria for MS (2005) are the currently recognized MS diagnostic criteria. The clinical subtypes of MS and their diagnosis are discussed in this article. Being informed of the diagnosis may be a stressful experience for the patient and this is also dealt with.     

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     

Predictors of quality of life among patients with multiple sclerosis: an Italian cross-sectional study

The Functional Assessment of Multiple Sclerosis (FAMS) quality of life (QoL) instrument is a disease-specific, self-report questionnaire that was developed originally for US English-speaking patients. Here, the psychometric properties of the FAMS QoL questionnaire for Italian-speaking patients with multiple sclerosis (MS) are evaluated and compared with the results from the original FAMS validation survey (n=377). Eighteen Italian centers and 344 patients with MS participated in the study. The overall reliability (as expressed by Cronbach's alpha value) of the FAMS score, and its subscale scores, was always over the threshold of 0.8. Patients with benign MS showed a better overall QoL compared with patients with relapsing-remitting MS (RRMS; p=0.017), whereas patients with RRMS had a better QoL than patients with primary progressive MS (PPMS). No difference in QoL was found between patients with PPMS and those with secondary progressive MS. The Italian FAMS questionnaire is a valid measure to assess the QoL concerns of patients with MS. FAMS is also easy to administer and is well accepted by patients.     

Neurochemical and morphological studies on demyelination in multiple sclerosis with special reference to etiological aspects

Summary Light microscopic studies were used as control for neurochemical studies and these showed that some micro plaques could be found also in areas which were normal on visual inspection. Also foreign cell infiltrates were found outside any clear plaque material. The number of these cells did not correlate with other findings like lipid or enzyme chemistry. In electronmicroscopic studies astrocytes demonstrated most lysosomes and phagocytosis of myelin. This increased lysosomal reaction was demonstrated also in biochemical analyses performed on MS biopsy specimens. Occasional nuclear changes like inclusion bodies and protrusion of inner nuclear membrane were observed suggesting some exogenous, possibly viral factor as an origin of the disease. Neurochemical studies showed that demyelination as a sense of decrease in myelin lipid and phosphohydrolase activity is only a later phenomenon and increased lysosomal activities possibly originating from various glial cells are found before demyelination. However myelin-like material found inside lysosomes suggests the early moderate demyelination before classical plaques can be found. Acid hydrolases were mostly increased at areas around plaques and encephalitogenic protein was not demonstrable at plaque areas. Our combined study suggests early changes of glial cells as a basic mechanism of the disease. However, the clarification of the basic course of these changes remains to be seen although nuclear changes may suggest a slow viral infection.Aided by a grant from Sigrid Juselius' Foundation.     

Malignant diseases among patients with multiple sclerosis

Summary The frequency of malignant diseases among 1866 living and 340 deceased multiple sclerosis (MS) patients was investigated in Finland. The study revealed a low prevalence (0.64%) and mortality (0.07%) rate of cancer among MS patients. The difference between MS patients and general population was significant. The highest rate was found in the group from 40 to 49 years while in the general population the rate of cancer among MS patients tended to fall after the age of 50. The possible role of selenium, one of the antioxidants in the pathogenesis of MS and cancer, is discussed because recent data have shown a very high negative correlation between selenium and cancer death rates.

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Zusammenfassung Die Malignomenfrequenz bei 1866 lebenden und 340 verstorbenen Multiple-Sklerose (MS)-Patienten wurde in Finnland untersucht. Dabei wurde eine niedrige Prävalenz-(0.64%) und Mortalitätsrate (0.07%) für Karzinom ermittelt. Der Unterschied zwischen den MS-Patienten und der Normalbevölkerung war signifikant. Die höchste Inzidenzrate war in der Altersgruppe von 40 bis 49 Jahren festzustellen. Anders wie bei der Normalbevölkerung nahm bei den MS-Patienten die Karzinomfrequenz nach dem fünfzigsten Lebensjahr ständig ab. Die mögliche Rolle Seleniums, eines Antioxydants, in der Pathogenese von MS und Karzinom wurde diskutiert, denn neue Ergebnisse haben eine hohe negative Korrelation zwischen Selenium und Karzinommortalität erwiesen.

     

Risk factors for increased multiple sclerosis susceptibility in the Iranian population

Multiple sclerosis (MS) is a complex autoimmune disease with increasing prevalence. Many factors have been assessed in relation to its development and its worldwide geographical and racial distribution. Therefore, we decided to conduct a nationwide case-control matched study to estimate the possible influence of putative risk factors on MS status in an Iranian MS population. Between January 2008 and September 2013, 1403 patients diagnosed with MS according to the Poser or McDonald criteria and 883 controls were studied. Of all patients, there were 921 women and 296 men (ratio 3.1:1) with a mean age of 32.6 ± 8.7 years. In the multivariate model adjusted for sex and age (±2 years), we found associated risk factors of MS to be: history of any allergic condition (Odds ratio (OR): 1.92, 95% Confidence interval (CI): 1.55–2.47, p < 0.001), and smoking (OR: 1.93, 95% CI: 1.31–2.73, p < 0.001). Sunlight exposure ⩾3 hours was found to be associated with a reduced risk of MS (OR: 0.23, 95% CI: 0.15–0.31, p < 0.001). As expected, cases were more likely to have a positive family history of MS than controls (OR: 1.91, 95% CI: 1.33–2.75, p < 0.001). A significant association was found between family history of other autoimmune diseases and MS risk (OR: 1.57, 95% CI: 1.18–2.09, p = 0.002). These results support the hypothesis that sun exposure is associated with a decreased risk of MS while smoking, autoimmune family history, MS family history, and personal allergy history are risk factors for MS susceptibility.     

Lipid composition of myelin in multiple sclerosis

Summary Myelin was isolated from histologically normal white matter and plaques from MS patients and from white matter of neurologically normal controls. No difference was found in the total lipid content. There were no detectable deficits in MS myelin of phosphoglycerides, plasmalogens or sphingolipids. Gangliosides and lysolecithin were not detected. Analysis of the fatty aldehyde composition of the phosphoglycerides and the fatty acid composition of the cholesteryl esters, phosphoglycerides and sphingolipids did not show any differences between the normal and MS myelin.This investigation was supported by Grant 484 from the National Multiple Sclerosis Society and by USPHS Grants HD 04575, NB 05464, GM-K6-19177.The postmortem specimens were provided from the International Tissue Bank supported by the National Multiple Sclerosis Society and administered by Wallace W. Tourtellotte, M.D., Ph.D.     

Natural history of multiple sclerosis: long-term prognostic factors

Several prognostic factors of long-term irreversible disability, mainly demographic and clinical, have been described in multiple sclerosis (MS). Most predictors have a minor influence on the long-term prognosis, and efforts are currently shifting toward finding relevant paraclinical predictors. By contrast, the study of prognostic factors has given some insights into the pathogenesis of MS, notably regarding the relation between relapses and long-term disability, and has emphasized the need to elucidate the exact mechanisms underlying neurodegeneration for the development of new therapeutic targets.     

Treatment of multiple sclerosis with mitoxantrone

Summary Ten multiple sclerosis patients, all with a rapid deteriorating disease profile, were treated with 12 mg/m² of the cytostatic agent mitoxantrone, administered every 3 months. This dosage is only 25% of what a patient with a solid tumour would normally receive during the same time period. In all treated patients the deterioration was stopped following the initial dosage; in four out of ten patients there was even an immediate improvement of the neurological status. Eight out of nine patients showed an improvement after 1 year as compared with their enrolment status; the other one remained stabile. In correlation with the clinical improvement, the mean P100 latencies of visual evoked potentials showed a reduction after 1 year. However, the changes identified through magnetic resonance imaging were even clearer than those seen clinically. At admission, this group of patients presented with a total of 169 gadolinium (Gd)-enhancing lesions. Only 10 lesions were enhancing in nine patients 12 months after the initiation of treatment. It appears that mitoxantrone accelerates the disappearance of Gd-enhancing lesions and prevents the development of new ones. Minimal side effects such as mild nausea and a slight faintness were evident in six patients and then for only 1–2 days.     

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.

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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.

     

多发性硬化血清麻疹、风疹和水痘-带状疱疹病毒IgG抗体水平及临床意义

目的通过检测多发性硬化(Multiple sclerosis,MS)患者血清中麻疹病毒、风疹病毒和水痘-带状疱疹病毒的免疫球蛋白G(Immunoglobulin G,IgG)抗体浓度,并进行扩展残疾状态量表(Expanded disability status scale,EDSS)评分,探讨上述病毒在MS发病中的临床意义及其与临床神经功能缺失的相关性。方法收集2013年9月-2015年2月郑州大学第一附属医院神经内科收治的50例MS患者急性期(复发期)的血清标本,其中临床孤立综合征(CIS亚组)22例,复发-缓解型MS(RRMS亚组)28例,对照组收集同一时期我院体检结果正常的37例健康志愿者的血清标本。采用双抗体夹心酶联免疫吸附方法(Enzyme linked immunosorbent assay,ELISA)测定并比较血清中3种病毒IgG抗体的浓度,分析血清中各病毒抗体水平与EDSS评分的相关性。结果 (1)MS病例组麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体的血清浓度高于对照组,差异具有统计学意义(P0.05);(2)CIS亚组患者血清中麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体水平低于RRMS亚组,EDSS评分亦低于RRMS亚组,差异均具有统计学意义(P0.05);(3)MS病例组血清中麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体与EDSS评分无相关性(P0.05)。结论 MS患者血清中的麻疹病毒、风疹病毒和水痘-带状疱疹病毒可能不仅与MS的发病相关,而且与疾病的复发有关。     

The multiple sclerosis trait and the development of multiple sclerosis: genetic vulnerability and environmental effect

The remarkably low rate of concordance of multiple sclerosis (MS) in monozygotic twins has never been fully explained but it implies the possibility of a systemic condition called the multiple sclerosis trait (MST), which is quite different from asymptomatic MS. It results from the action of an antigenic challenge on the immune system of a genetically vulnerable person that does not cause damage to the nervous parenchyma; it may never evolve into the disease MS. A subsequent environmental viral-antigenic event in some MST-carriers can change the trait into the disease. This event could be an infection, which need not be symptomatic, or a vaccination. The MS may become symptomatic, remain asymptomatic, or manifested only by lesions visible by MRI. It is likely that the development of the MST, called activation, occurs early in life, while the transition from MST to MS, called acquisition, takes place at puberty in most patients. Differences in prevalence between pre-puberal migrants, and the locally born children of migrants, and their population of origin may also be explained by the MST.     

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.