Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study

In the present study the relation between human leukocyte antigen (HLA), optic neuritis (ON) and multiple sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males). HLA-A and -B typing by microlymphocytotoxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON. The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, whilst A23, A26, and A30 showed a significant decrease in these patients. HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients. HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients. Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, whilst the frequency of HLA-DRB1*07 and *11 was much higher in ON patients. In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group. In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.     

Cerebrospinal fluid levels of brain specific proteins in optic neuritis

This study evaluates levels of cerebrospinal fluid (CSF) brain-specific proteins (BSP) in subjects with optic neuritis (ON) who are at high risk of progression to multiple sclerosis (MS). Forty-one subjects had acute ON and 17 subjects with other neurological diseases (OND) served as controls. Twenty-one subjects with ON had white matter lesions on magnetic resonance imaging (MRI) and intrathecal synthesis of oligoclonal IgG bands (OB) consistent with being at high risk of progression to MS; eight of whom later were diagnosed with clinically definite MS (CDMS). Levels of S100B, ferritin and two neurofilament heavy chain phosphoforms (NfH(SM134) and NfH(SM135)) were analysed using ELISA technique. A putative index of 'axonal health' was expressed as a ratio of NfH(SM134) to NfH(S135). NfH(SM134) and the NfH(SM134:SM135) were significantly elevated in subjects with ON compared to controls. No significant differences in levels of CSF BSP were seen between ON subjects with CDMS plus those at high risk of progression to MS and ON subjects with normal MRI and negative CSF analysis. In conclusion, there is evidence of axonal damage in subjects who present with ON, which is independent of the diagnosis of CDMS.     

MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT

We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard.     

Study of HLA as a predisposing factor and its possible influence on the outcome of multiple sclerosis in the sanitary district of Calatayud, northern Spain.

The relationship between multiple sclerosis (MS) and the HLA antigens DR2 and DQ1 is well recognised, but, in Spain, it has not been clearly defined. The aim of our study was to investigate the relationship between MS and HLA antigens in the sanitary district of Calatayud, northern Spain, and to correlate these antigens with the progression of the disease. Thirty-four patients were selected from a long-term (October 1990 to July 1996) prospective survey in the region where there was a prevalence rate of 58 per 100,000 population. The HLA antigens were determined in 31 patients. A control group of 895 people of Caucasian race was recruited from the same population. We performed serologic tests on all participants. Nucleotide typing was carried out in DR2-positive patients. The most frequent antigens in excess in MS were: A19 (odds ratio, OR: 2.29, p = 0.04), B5 (OR: 2.85, p = 0.02), B41 (OR: 7.65, p = 0.04), CW7 (OR: 3.4, p = 0.004), DR6 (OR: 6.18, p = 0.0001) and DR10 (OR: 3.4, p = 0. 004). The DR2 antigen was also more frequent in MS patients (39%) than in controls (19%; OR: 2.69, p = 0.01). All positive DR2 patients showed the DR15(2) split but not the DR16(2) split. The frequency of antigens CW4 and DR1 was lower in MS patients than in controls. The CW4 antigen was detected in 12% of the patients and in 33% of the controls (OR: 0.28, p = 0.04). The DR1 antigen was found in 20% of the controls and in none of the MS patients (OR: undefined, p = 0.01). The DQ1 antigen was observed in 68% of the patients and in 50% of the controls (OR: 2.1, p = 0.07). We did not find any relationship between HLA antigens and progression of the disease. Although we found that DR2 antigen is linked to MS, we also found other antigens related to the disease. This suggests a genetic heterogeneity in our geographic area. We also concluded that the DR1 antigen may play a protective role, as it was detected in 20% of the controls and in none of the MS cases.     

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].     

DQB1*0602 allele shows a strong association with multiple sclerosis in patients in Malaga,Spain

BACKGROUND: The human leukocyte antigen (HLA) class II DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) has been associated with multiple sclerosis (MS) in all ethnic groups and very strongly in Caucasians. AIM: To investigate the possible HLA class II (DRB1, DQA1 and DQB1) associations with MS in Malaga, southern Spain. METHODS: We analysed the HLA class II sub-regions DRB1, DQA1 and DQB1 by polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (PCR/SSO) for DRB1 and DQB1 and with sequence-specific primers (PCR/SSP) for DRB1 subtypes and DQA1. Possible HLA class II associations with clinical MS characteristics were investigated in 149 subjects with and 160 without MS. RESULTS: Associations were detected between MS and the HLA class II alleles DRB1*1501 (45.6 % vs. 21.3%, p=0.001), DQA1*0102 (44% vs. 29.4%, p=0.001) and DQB1*0602 (45% vs. 20.6%, p=0.001). The DR2 haplotype (DRB1*1501, DQA1*0102, DQB1*0602) was associated with MS (43.6 % vs. 20%, p=0.002). DQB1*0602 was the only allele that maintained an association with MS in a logistic regression model. No HLA class II alleles or genotypes were significantly associated with any clinical characteristics of MS. CONCLUSIONS: Our results confirm the positive association of the DR2 haplotype with MS, particularly the allele DQB1*0602, in the population studied. DR4 was not associated with the disease in Malaga. HLA class II alleles or haplotypes were not associated with clinical or demographic characteristics, or clinical form or severity of MS.     

HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population

BACKGROUND: An association between HLA antigens and susceptibility to multiple sclerosis (MS) has been established, especially in Caucasian populations. Such associations have not been as clearly defined in many Arab populations, where even the frequencies of specific HLA antigens remain unclear OBJECTIVE: The study was designed to (i) investigate the frequencies of HLA Class I and II antigens in Kuwaiti Arabs with MS, and; (ii) assess possible inter-relationships between HLA Class II antigens and such clinical phenotypic variables in MS as age at onset, gender, disease subtype and scale of disability. SUBJECTS AND METHODS: HLA Class I (A, B, C) and Class II (DR, DQ) antigens' tissue-typing was performed by the standard complement-dependent microlymphocytotoxicity technique in two groups of age- and sex-matched Kuwaiti subjects: (i) 67 patients with definite MS (48 relapsing remitting, 19 relapsing-progressive) and (ii) 145 unrelated healthy controls. The frequencies of specific HLA types were then compared between patients with controls, and in the former, related to specified clinical parameters. RESULTS: The frequencies for the Class I antigens: A9, A10, A19, A33, B5 and CW4 appeared higher with the presence of MS, although the numbers of positive subjects were rather low. For the Class II antigens, frequencies of DR4, DQ5, DQ6, DQ7 and DQ8 were increased while those for DR6 and DR1 were decreased in the patients with MS. HLA types DR15 and DR4 were present at higher frequencies in patients with a younger age at disease onset; DR15 also appeared more frequent in the female patients. CONCLUSION: There is a trend towards an association between HLA Class II antigens (DR4, DQ6, DQ7 and DQ8) and MS in Kuwaiti subjects. Additionally, it appeared that DR4 and DR15 were more frequent in females and those with an early onset of the disease. These patterns of HLA Class II determinants of susceptibility to MS differ from reports in some other populations, and may reflect the recognized variability in genetic influence on HLA and disease expression.     

Evaluation of central nervous system involvement in uncomplicated optic neuritis after prolonged follow-up

Magnetic resonance imaging (MRI), multimodal evoked responses (ER) and HLA antigens were examined in 10 patients with idiopathic acute optic neuritis (ON) without any clinical symptoms or signs of multiple sclerosis (MS) during 9-14 years. In MRI, abnormalities compatible with MS were seen in 4 patients. In spite of clinically unilateral ON, a bilateral abnormality in visual evoked responses (VER) was seen in 3 of 9 cases. Brain stem auditory evoked responses (BAER) were normal in all cases, short latency somatosensory evoked response (SER) in all but one. The cerebrospinal fluid at time of ON showed signs of demyelination in one case only. The frequency of HLA antigens DR2 (78%) and B18 (40%) was significantly increased in comparison to healthy controls. MRI seems to be the most sensitive method in the detection of cerebral lesions of MS, especially in mild or asymptomatic forms of the disease. The present techniques are, however, mostly unable to demonstrate optic nerve lesions which more reliably can be evaluated by VERs. The question whether idiopathic ON represents a form of MS solely, cannot be resolved.     

HLA-DRB1基因型与北方汉族多发性硬化易感性的研究

目的 探讨人类白细胞抗原(HLA)-DRB1基因型与中国北方汉族多发性硬化(MS)的关联.方法 应用序列特异性引物-聚合酶链反应(PCR-SSP)技术检测58例中国北方汉族MS患者及63名健康对照者的HLA-DRB1基因型分布;同时将MS患者分为西方型MS和视神经脊髓炎(NMO)两亚组,对其DR4和DR15基因频率进行比较.结果 与对照组比较,MS患者DR15和DR4等位基因频率显著升高(分别为P=0.025,P=0.003);此外,NMO亚组DR4频率显著高于西方型MS(P=0.013).结论 我国北方汉族人MS与HLA-DRB1等位基因的关联与西方人群有所不同,DR15可能是MS的易感基因,而DR4则可能为我国汉族人NMO的易感基因.关联基因的差异可能是导致东西方MS病变部位不同的原因.     

HLA-DR15 is associated with lower age at onset in multiple sclerosis

To date, more than a dozen studies have investigated the role of HLA genes in determining clinical course and disease severity in multiple sclerosis (MS); in each of these studies, however, patient sample size has been small, and no consistent pattern has emerged from the results. For the present study, we determined HLA class II genotypes and catalogued clinical and demographic data for a total of 948 patients, making our data set the largest ever used to investigate HLA genes in MS. Our goals were both to investigate the impact of HLA-DRB1 alleles on clinical course and disease severity in MS and to compare the frequencies of the established susceptibility allele DR15 in various clinicodemographic subgroups of MS patients. We found that, in addition to DR15, DR17 is positively associated with susceptibility to MS; that none of the HLA-DRB1 alleles influences course or outcome in MS; that carriers of DR15 are prone to MS development at an earlier age than noncarriers; and that differences in DR15 positivity rates, after stratification for diagnostic category and examination results, seem to reflect a gradient of phenocopy contamination, with rates increasing in proportion to the degree of clinical or paraclinical verification of the MS diagnosis.     

Serial MRI, VEP, SEP and biotesiometry in acute optic neuritis: value of baseline results to predict the development of new lesions at one year follow up

Introduction In an attempt to establish the value of MRI, VEP, SEP, and biotesiometry in monitoring disease evolution we undertook a one year follow up study of 70 untreated patients with acute optic neuritis (ON). Material & methods – ON was monosymptomatic in 48 patients (bilateral in 10) and part of clinically definite multiple sclerosis (CDMS) in 22 patients, examined as mentioned below. Results – Results are given at onset and at follow up (in brackets). In monosymptomatic ON, brain MRI was abnormal in 53% (53%), VEP in the eye with acute ON in 79%> (71%), VEP in the clinically unaffected eye in 34% (47%), SEP in 25% (23%), and biotesiometry in 29% (17%). In CDMS, brain MRI was abnormal in 95% (95%), VEP in the eye with acute ON in 86% (77%), VEP in the clinically unaffected eye in 50% (64%), SEP in 55% (50%), and biotesiometry in 63% (53%). Only minor changes in test scores were observed after one year except for significant improvement of VEP in eyes with acute ON. Eight of 32 patients, characterized by at least one abnormal paraclinical test at onset of monosymptomatic ON, had developed CDMS versus none of 16 patients with normal paraclinical results (p = 0.03; Fisher). Conclusion – Patients with monosymptomatic ON with paraclinical signs of multifocal involvement at onset had an increased risk of developing CDMS. No single test predicted the evolution of CDMS, perhaps due to the relatively short follow up time.     

人类白细胞抗原DRB1基因与多发性硬化遗传易患性研究

目的　分析多发性硬化遗传易患的分子免疫遗传背景。方法　采用聚合酶链反应序列特异性引物（ＰＣＲＳＳＰ） 联合技术对４５ 例病例组和１０５ 例正常对照组人类白细胞抗原ＤＲＢ１ 基因（ＨＬＡＤＲＢ１） 进行基因分型。结果　病例组ＨＬＡＤＲ２ 基因频率高于正常对照组，优势比为３．３２１ ，有统计学意义（ Ｐ＜ ０．０１）。结论　ＨＬＡＤＲ２ 基因与多发性硬化遗传易患相关联，提示可能还存在保护性基因。     

HLA‐DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population

Background and objective: The association of HLA‐DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA‐DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population. Methods: HLA‐DRB1 typing was performed by PCR‐SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS. Results: The HLA‐DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR) = 2.07, 95% CI = 1.64–2.60, P < 0.001). In the univariate analysis, the DRB1*01 and DRB1*04 alleles were associated with a worse prognosis when considering the time to reach an EDSS of 6, whereas the DRB1*03 was correlated with a better outcome. In the multivariate analysis, the alleles*01 and *04 were demonstrated to be independent factors to have a worse prognosis. Conclusions: HLA‐DRB1*15 is associated with MS when comparing patients with unrelated healthy controls in a Spanish population. The HLA‐DRB1*01 and HLA‐DRB1*04 alleles are related to a worse prognosis when considering the time taken to reach severe disability.     

Association of HLA‐DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort

Background and objective: The HLA‐DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA‐DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS. Methods: The HLA‐DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA‐DRB1 allelic frequencies were compared between OCB‐positive and OCB‐negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA‐DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB. Results: We found 206 OCB‐positive and 62 OCB‐negative patients. The HLA‐DRB1*15 allele in OCB‐positive patients had a higher frequency when compared with OCB‐negative patients (39.3% in OCB‐positive vs. 16.1% in OCB‐negative, OR = 1.38 95% CI = 1.18–1.61, P < 0.001). The other alleles did not show differences. When we compared with controls, the HLA‐DRB1*15 allele was associated with the disease only in the OCB‐positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB. Conclusions: HLA‐DRB1*15 allele is associated with OCB‐positive patients with MS when studying a Spanish MS population.     

Paraclinical tests in acute-onset optic neuritis: basal data and results of a short follow-up

Up to now it is still doubtful whether there is a real risk of developing multiple sclerosis (MS) after initial monosymptomatic optic neuritis (ON). In this study we evaluated 43 patients with isolated acute-onset ON, in order to demonstrate the presence of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and any additional clinically silent central nervous system (CNS) lesions. All examinations were performed from 5 days to 4 months (mean 43 days), from the onset of visual disturbances. Brain magnetic resonance imaging (MRI) detected white matter areas with increased signal in 21 patients (49%), while somatosensory and brainstem auditory evoked potentials revealed CNS abnormalities in only 5 patients (12%). OBs were present in the CSF of 20 patients (46%). Visual evoked potentials were abnormal in 39 patients (91%). Seven out of the 37 patients (19%) with at least one year follow-up, (mean duration of the follow-up = 32 months, range = 12-74), developed clinically definite MS (CDMS). All 7 patients had positive brain MRI and 6 had positive CSF examination at the basal evaluation. Our data suggest that MRI and CSF-OBs are the most reliable means of identifying patients with isolated ON who subsequently develop CDMS. They may therefore have a predictive value in defining MS risk.     

Long-term follow-up of isolated optic neuritis: the risk of developing multiple sclerosis, its outcome, and the prognostic role of paraclinical tests

We evaluated the risk of developing clinically definite multiple sclerosis (CDMS) after an acute attack of isolated optic neuritis (ON) in 112 patients, in relation to demographic and paraclinical findings. Patients were examined by brain MRI, CSF analysis, and multiple evoked potentials (EPs); 10 were lost to follow-up, and the other 102 were enrolled in a prospective study (follow-up duration 6.3 ± 2.2 years). Of these, 37 (36.3%) developed CDMS after a mean interval of 2.3 ± 1.6 years. The risk of developing CDMS was 13% after 2 years, 30% after 4, 37% after 6, and 42% after 8 and 10 years. Gender, age, and season of ON onset did not affect the risk. MS occurred in 37 of 71 patients (52.1%) with one MRI lesion or more; no patient with a normal MRI developed the disease. MS developed more frequently in patients with intrathecal IgG synthesis than in those without (43% vs. 28%), but the difference was not statistically significant. Multiple EPs showed a slight predictive value only including somatosensory EPs of the lower limb. Multiple sclerosis was mild in most cases (EDSS 2.2 ± 1.9). The EDSS was less than 4 in 32 cases (86%), between 4 and 6 in 2 (5%), higher than 6.5 in 3 (8%). Received: 27 July 1998 Received in revised form: 3 February 1999 Accepted: 7 February 1999     

Sensitivities and predictive values of paraclinical tests for diagnosing multiple sclerosis

The sensitivities and predictive values of visual, somatosensory, and brain auditory evoked potentials (EPs), cerebrospinal fluid oligoclonal banding (CSF-OB) and magnetic resonance imaging (MRI) were evaluated for the early diagnosis of clinically definite multiple sclerosis (CDMS). Paraclinical evidence of asymptomatic lesions allows a diagnosis of CDMS. Eighty-two patients in whom MS was suspected but diagnosis of CDMS was not possible entered the study prospectively. Paraclinical examinations were performed at entry. Patients were examined and underwent EPs every 6 months, and MRI yearly. After a mean follow-up of 2.9 years, 28 patients (34%) had developed CDMS (McDonald-Halliday criteria). The initial MRI was strongly suggestive of MS in 19 of these (68%), while 27 (96%) had at least one MS-like abnormality in the initial MRI. CSF-OB and EPs had lower sensitivities. CDMS developed during follow-up in 19 of the 36 patients (53%) who had an initial MRI strongly suggestive of MS but in only 1 of the 25 who had normal MRI when first studied. These results support previous conclusions that MRI is the most sensitive test for detecting white matter asymptomatic lesions, and the most predictive for the diagnosis of CDMS.Presented in part at the Third meeting of the European Neurological Society, Lausanne (Switzerland), June 1992     

Magnetic resonance imaging of the head in the diagnosis of multiple sclerosis: a prospective 2-year follow-up with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT

We previously compared the diagnostic capabilities of MRI of the head with CT, evoked potentials, and CSF oligoclonal banding (OB) analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). To examine the ability of MRI and other paraclinical tests to predict the diagnosis of clinically definite MS (CDMS), we did a systematic clinical follow-up of 200 patients who were previously reported. In that study, 85 of 200 could be diagnosed as having laboratory-supported definite MS (LSDMS). In follow-up, we excluded one patient diagnosed as LSDMS who in retrospect was considered to have had CDMS at entry and 15 patients who were eventually diagnosed as having other diseases. After a mean follow-up of 2.1 years, 55 of the remaining 184 patients (30%) had developed CDMS. Thirty-eight of 84 patients with an original diagnosis of LSDMS (45%) and 17 of the remaining 100 patients with suspected MS (17%) had become CDMS. Forty-six of the 55 patients who developed CDMS in follow-up (84%) had an initial MRI that was strongly suggestive of MS. Fifty-two of those 55 CDMS patients (95%) had at least one MS-like abnormality on MRI when originally studied. In contrast, 38 of 55 (69%) had CSF OB, 38 of 55 (69%) had an abnormal VEP, 35 of 55 (64%) had an abnormal SEP, and 21 of 55 (38%) had an abnormal CT when first studied. MRI was the most sensitive single paraclinical test for predicting CDMS. CDMS developed during follow-up in 46 of the 94 patients (49%) whose initial MRI was strongly suggestive of MS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple sclerosis,sleep latencies and HLA antigens

Summary The role of HLA antigens, and HLA-DR2 in particular, in the determination of mean sleep onset latencies (MSOLs) in multiple sclerosis (MS) was studied. It has been suggested that this antigen may play a part in the reduction of MSOLs, since nearly 100% of patients suffering from narcolepsy are DR2-positive. A multiple sleep latency test was performed in 37 patients suffering from MS without spontaneous complaints of sleep disturbances and who were typed for HLA-A, B, C, DR and DQ. The MSOL was reduced in a total of 21 patients, in only 7 of 15 DR2-positive patients and in 12 of 21 DQw1-positive patients. However, it was reduced in 13 of 16 B8- or B14-positive patients. In contrast with this, in the absence of an early sleep onset (MSOL >30 min), no HLA antigens were found to be over-represented when considered individually; only those patients positive for a group of cross-reacting HLA antigens (B5, B15, B18, B21 or B35) had an MSOL greater than 30min. These results suggest that the genes which code for the DR2 or DQw1 antigens, which are present in nearly 100% of narcoleptics, are not solely responsible for the appearance of an early sleep onset in MS.     

Short-term prognosis in early relapsing-remitting multiple sclerosis

OBJECTIVE: To characterize a group of patients with early MS using prognostic factors and to determine whether these prognostic factors impact on short-term prognosis. METHODS: Data were collected prospectively on 98 patients newly diagnosed with MS in our MS clinic between 1990 and 1998 (average follow-up, 37 months from the time of onset of clinically definite MS [CDMS]). Six prognostic factors were recorded: age at onset, symptoms at onset, MRI status at onset and at diagnosis of CDMS, interval between the first and second attack, attack frequency in the first 2 years, and completeness of recovery from initial attacks. Completeness of recovery was determined using Expanded Disability Status Scale scores (EDSS). Progression was determined by final EDSS and changes in EDSS between initial presentation and final follow-up. RESULTS: Patients predicted to have low risk of progression of MS based on the prognostic factors represented 17% of our patient population (0 to 1 risk factor for progression). The patients with high risk of progression (4 to 6 risk factors) represented 24% of patients. Patients with a high number of risk factors did significantly worse than those with a small or medium number of risk factors in terms of final EDSS and progression to higher EDSS. At the time of diagnosis of CDMS, MRI findings suggestive of MS were seen in 84% of patients (suspicious in 13%, negative in 3%). CONCLUSION: Short-term prognosis was influenced by the presence or absence of a high number of these six risk factors.