Regional And Temporal Variation In The Incidence Of Multiple Sclerosis In Finland 1979-1993
Sumelahti M, Tienari PJ, Wikstrom J, Palo J, Hakama M
NeuroEpidemiology 2000 Mar;19(2):67-75
Univ of Tampere, School of Public Health, Tampere, Finland
Previous surveys in Finland from the 1960s have documented an uneven geographic distribution of Multiple Sclerosis (MS). In the present study, the incidence of MS was studied during 1979-1993 in the Western Vaasa and Seinajoki regions and in Southern Uusimaa.
The overall difference between the Western and Southern regions persisted; 8.7 per 100,000 in the western, and 5.1 per 100,000 in the southern region.
The incidence of 11.6 per 100,000 in Seinajoki was more than twofold greater than the 5.2 per 100,000 incidence found in neighboring Vaasa.
An increasing incidence trend was observed for men in Seinajoki, and a decrease for both sexes in Vaasa, while in Uusimaa the incidence remained stable for both sexes.
The different incidence trends could not be readily explained by differences in case ascertainment but suggest the effect of environmental factors that have modulated the incidence of MS during the 15-year study period.
Copyright 2000 S. Karger AG, Basel
Ebers GC, Koopman WJ, Hader W, Sadovnick AD, Kremenchutzky M, Mandalfino P, Wingerchuk DM, Baskerville J, Rice GP
Brain 2000 Mar;123(Pt 3):641-649
Univ of Western Ontario, Dept of Clinical Neurological Sciences, London, Ontario, Canada
We have examined the Demographics and long-term outcome of 1044 patients with Sporadic and Familial Multiple Sclerosis in a population-based cohort from London, Ontario.
The mean follow-up was 25 years in duration, and by this time most patients had reached the unambiguous endpoint scores of the Kurtzke Disability Status Scale (DSS), DSS 6, 8 or 10.
An affected family member was identified in 19.8% of the total population, and this subgroup was further divided arbitrarily into the following three groups by the type and number of relatives affected:
- First degree only
- First degree plus others
- Second or Third degree
The outcome in these groups was compared with that for those patients who, at a mean 25 year follow-up, had no relatives known to be affected.
Familial cases closely resembled those remaining Sporadic in both Demographics and outcome, although onset in the most heavily loaded families was earlier and male/female ratio was greater.
The times to DSS 6, 8 and 10 did not differ significantly when Sporadic, Familial and Familial Subgroups were compared.
These results provide no clinical support for viewing Familial Multiple Sclerosis as distinct from the Sporadic Form. The observed recurrence rate for siblings in a strictly defined Epidemiological sample was 3.5%, much as projected.
These results validate the recurrence risks which have previously been derived from age-corrected data for these First-degree relatives.
McGavern DB, Murray PD, Rivera-Quinones C, Schmelzer JD, Low PA, Rodriguez M
Brain 2000 Mar;123(Pt 3):519-531
Mayo Clinic and Foundation, Molecular NeuroScience Program and Depts of Neurology and Immunology, Rochester, Minnesota, USA
Recent pathological studies have re-emphasized that Axonal injury is present in patients with Multiple Sclerosis, the most common DeMyelinating Disease of the CNS in humans.
However, the temporal profile of DeMyelination and Axonal Loss in Multiple Sclerosis patients and their independent contributions to clinical and ElectroPhysiological abnormalities are not completely understood.
In this study, we used the Theiler's Murine EncephaloMyelitis Virus model of Progressive CNS inflammatory DeMyelination to demonstrate that DeMyelination in the Spinal Cord is followed by a loss of medium to large Myelinated fibers.
By measuring Spinal Cord Areas, Motor-Evoked Potentials, and Motor Coordination and Balance, we determined that Axonal Loss following DeMyelination was associated with ElectroPhysiological Abnormalities and correlated strongly with Reduced Motor Coordination and Spinal Cord Atrophy.
These findings demonstrate that Axonal Loss can follow Primary, Immune-mediated DeMyelination in the CNS and that the severity of Axonal Loss correlates almost perfectly with the degree of Spinal Cord Atrophy and Neurological Deficits.
Repertoire Dynamics Of Autoreactive T-Cells In Multiple Sclerosis Patients And Healthy Subjects: Epitope Spreading Versus Clonal Persistence
Goebels N, Hofstetter H, Schmidt S, Brunner C, Wekerle H, Hohlfeld R
Brain 2000 Mar;123(Pt 3):508-518
Ludwig-Maximilians University, Max Planck Institute for NeuroBiology, Dept of NeuroImmunology, Martinsried and Dept of Neurology and Institute for Clinical NeuroImmunology, Munich, Germany
AutoAntigen-specific T-Lymphocytes are present in patients with AutoImmune Disease and in normal subjects. Little is currently known about the temporal variation (dynamics) of the Immune repertoire of these AutoReactive T-Cells.
We analyzed the long-term variation of the Immune repertoire of T-Cells specific for Myelin Basic Protein (MBP) in five untreated patients with Multiple Sclerosis and four normal control subjects over a mean observation period of 6 years.
MBP-specific CD4+ T-Cell lines were selected with purified human MBP, and their Epitope specificity was mapped with overlapping synthetic peptides.
Three distinct patterns of repertoire development were observed:
- Two patients and three control subjects maintained a broad Epitope response with fluctuations over time.
- Two patients initially showed a focused response that broadened over the course of 6 years; this finding could be described as IntraMolecular Epitope Spreading.
- In one patient and one control subject, a strikingly focused response, which was directed to a cluster of nested Epitopes in the MBP region 83-102, persisted over time.
T-Cell receptor Vbeta sequence analysis allowed us to trace individual Clones of MBP-specific T-Cells for up to 7 years in the Peripheral Circulation in four of the five patients and three of the four controls.
Suggesting that the long-term persistence of MBP-Specific T-Cell Clones is a common feature of the T-Cell repertoire not unique to Multiple Sclerosis.
The persisting MBP-specific T-Cell Clones were not detectable in the blood of one of the patients by Complementarity-Determining Region (CDR)-3 SpectraTyping, indicating that their frequency does not exceed 1 in 5000 T-Cells.
The temporal characteristics of the MBP-specific T-Cell repertoire described here are relevant to therapeutic strategies targeting AutoAntigen-Specific T-Cells in Multiple Sclerosis and other AutoImmune Diseases.
Accumulation Of Clonally Related B-Lymphocytes In Multiple Sclerosis CerebroSpinal Fluid
Colombo M, Dono M, Gazzola P, Roncella S, Valetto A, Chiorazzi N, Mancardi GL, Ferrarini M
J Immunol 2000 Mar 1;164(5):2782-9
Istituto Nazionale per la Ricerca sul Cancro, Servizio di Immunologia Clinica, Genova, Italy; Universita degli Studi di Milano, Istituto di Medicina Interna, Dipartimento di Scienze Neurologiche e della Visione,
Universita degl, Milan, Italy
PMID# 10679121; UI# 20143876
The accumulation of B-Lymphocyte Clones in the CerebroSpinal Fluid (CSF) of patients with Multiple Sclerosis (MS) and patients with other Neurological Disorders was investigated using PCR technologies.
OligoClonal B-Cell accumulations were detected in 10 of 10 MS patients, but only in 3 of 10 of the patients with Other Neurological Disorders.
Analyzes of the Ig V(D)J sequences on the CSF from MS patients disclosed that VH3 and VH4 Genes were extensively mutated compared with germline sequences.
Moreover, a substantial proportion of the molecular Clones analyzed shared the same third CDR of the H chain variable region Gene (HCDR3) and the same VH Genes, albeit with different numbers and locations of point mutations, thus indicating an ongoing process of IntraClonal Diversification.
A larger number of Clonally related VH sequences could be obtained by using a VH3 gene-specific PCR so that Genealogical trees depicting the process of diversification could be drawn.
Analyzes of the Ig V(D)J from the CSF of a patient with Viral Meningitis and OligoClonal B-Cell accumulations revealed that VH3 Genes were extensively mutated. However, no IntraClonal diversification could be observed even using VH3 gene-specific PCR methodologies.
Clone-specific PCR and sequencing was used to detect the V(D)J found in the CSF of one MS patient in the PBL of the same patient.
Only 1/3 of the V(D)J sequences investigated could be demonstrated in the PBL, indicating that the V(D)J Genes utilized by B-Cells in the CSF are much less represented in the PBL.
Collectively, the data suggest that in MS there is a Compartmentalized Clonal Expansion.
Prevalence Of Multiple Sclerosis In The L'Aquila District, Central Italy
Totaro R, Marini C, Cialfi A, Giunta M, Carolei A
J Neurol NeuroSurg Psychiatry 2000 Mar;68(3):349-352
Univ of L'Aquila, Dept of Neurology, L'Aquila, Italy
To estimate the prevalence of Multiple Sclerosis in the L'Aquila district, central Italy.
All available case sources were screened. Definite and probable cases of Multiple Sclerosis, classified according to the Poser Criteria, were considered as prevalent cases.
On the prevalence day, 31 December 1996, 158 patients (105 women and 53 men; ratio 2:1) affected by Definite (n=131) or Probable (n=27) Multiple Sclerosis were alive and resident in the L'Aquila district.
Mean (SD) age was 38.4 (11.9) years (38.9 (11.7) years for women and 38.5 (12.3) years for men, p=0.9).
The overall crude prevalence was 53.0/100 000 (95% confidence interval (95% CI)=45.4-62.0); 68.4/100 000 (95% CI=56.5-82.8) in women, and 36.7/100 000 (95% CI=28.1-48.0) in men.
The prevalence was similar (55.9/100 000) when standardized to the 1996 European population.
Mean (SD) Age At Onset of Multiple Sclerosis was 29.4 (9.6) years and mean (SD) duration of the disease was 9.4 (7.4) years, without any significant difference between sexes.
Mean age at onset was significantly higher in patients with the Primary/Progressive than in those with the Relapsing/Remitting course (p=0.0002, Scheffe's test).
The prevalence found in the L'Aquila district gives support to the consideration of Italy as an area in which Multiple Sclerosis has been shown to have high prevalence at least in the populations that were surveyed recently.