传统型和视神经脊髓型多发性硬化临床特征的比较

目的:分析和比较视神经脊髓型多发性硬化(OS-MS)与传统型多发性硬化(C-MS)患者的临床特征。方法:在苏州地区收集99例按照McDonald诊断标准(2001)确诊为MS患者(其中C-MS73例,OS-MS26例)的临床资料,并结合实验室及相关检查的结果进行分析比较。结果:与C-MS相比,OS-MS患者中女性更多见,首发症状以视力减退和运动障碍最常见,整个病程中运动障碍、感觉障碍及视力减退的发生率较高,预后较差。2组患者在首次发病年龄、病程等方面未见显著差异。结论:C-MS与OS-MS患者在临床特征方面存在一定的差异。     

Antinuclear and antiphospholipid antibodies in patients with multiple sclerosis

The prevalence of autoantibodies in multiple sclerosis (MS) patients and their clinical associations differ between various studies. This study investigated antiphospholipid and antinuclear antibodies in 85 patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) with regard to their association with demographic features, MS specific clinical features and symptoms of connective tissue diseases. Autoantibodies tested included antinuclear antibodies (ANA) with their specificities and anticardiolipin (aCL) and anti-beta-2-glycoprotein I (anti-β2GPI) antibodies. Antinuclear antibodies were more prevalent in MS patients than in controls (63.5% vs. 3.3%; p?相似文献   

Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores

There were 21 patients with rapidly progressive multiple sclerosis (MS) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell (HSC) support with no 1-year mortality. Following transplantation, one patient had a confirmed acute attack of MS. Neurologic progression defined by the expanded disability status scale (EDSS) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less. In 8 of 12 patients with high pretransplantation disability scores (EDSS > 6.0), progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration. There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment. Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation (HSCT) are not effective for patients with progressive disease and high pretransplantation disability scores. Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity. Specifically, more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup.     

Therapeutic plasma exchange combined with immunomodulating agents in secondary progressive multiple sclerosis patients

Multiple sclerosis (MS) is the most common cause of neurological disability. Therapeutic plasma exchange (TPE) has been used in the management of patients with MS with equivocal efficacy. With this work we would like to present our experience with 10 patients (seven male and three female, mean age 34 years [range 27-53 years]) with secondary progressive MS, who were treated with immunomodulating agents and who also underwent TPE. The patients' expanded disability status scale (EDSS) score of entry to the study varied from 5.0 to 6.5. One year before study entry all patients showed a marked deterioration (12 months before starting TPE they had been rated 4.5-5.5 on the EDSS). TPE was performed three times a week for two weeks and thereafter once a week, or once a month for the stable patients. The machine used was the Cobe Spectra and albumin 5% was the replacement fluid. Peripheral veins were used in nine patients and indwelling vascular access was required in one patient. Eighteen months later, patients stopped taking the immunomodulating agent therapy and continued only with TPE. No side-effects occurred during the TPE session. After 36 months of TPE therapy, five patients were stabilized in their disability, while two patients showed a minor progression of the disease (an additional 0.5 degree in disability as determined by the EDSS). No relapses occurred during TPE. Three patients stopped the therapy: one patient because of persistent nausea and two patients for reasons unrelated to TPE. Periodic TPE was associated with reduced accumulation of neurological deficits (as documented by EDSS) in patients with secondary progressive MS.     

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis

High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5-7.5) and 56 (44-65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability. One patient improved significantly (by 1.0 point on EDSS) after the mobilisation. Two mobilisation failures were observed. No life-threatening events occurred during the transplantation. All grafted patients, except one, at least stabilised their disability status. One patient improved significantly (by 1.5 points on EDSS), two patients improved slightly (by 0.5 points on EDSS), one patient worsened by 1.0 point on the EDSS in 10 months. Improvement occurred with a delay of 2-4 months. Median EDSS and SNRS of grafted patients at the last follow up were 6.5 (5.5-8.5) and 64 (39-73), respectively with median follow-up of 8.5 months. Further follow-up is needed to determine the disease course after complete immune reconstitution. Bone Marrow Transplantation (2000) 25, 525-531.     

Clinical and laboratory features of in-patients with multiple sclerosis in a University Hospital in Tokyo from 1988-2002

OBJECTIVE: The aim of this study was to analyze the clinical and laboratory features of each subtype of multiple sclerosis (MS) (relapsing-remitting, primary progressive, and secondary progressive) in the Tokyo metropolitan area. METHODS AND PATIENTS: We retrospectively analyzed the medical records of 104 consecutive patients with a diagnosis of MS, who had been admitted to our university hospital from 1988 to 2002. They all met criteria for definite MS, by clinical or laboratory standards. RESULTS: Eighty-four (80.8%) patients were classified as having relapsing-remitting MS, while 8 patients (7.7%) and 12 patients (11.5%) were classified as having primary progressive MS and secondary progressive MS, respectively. A significant female predominance existed in the relapse-remitting MS (female : male=2.4 : 1) cohort, but this ratio was 1 : 1 in both primary progressive and secondary progressive MS. The age at onset was older in the primary progressive MS (36.6+/-17.1 years of old) population than in either the relapsing-remitting MS (27.9+/-11.1) or the secondary progressive MS (27.8+/-11.5) subjects. Although the duration of illness was similar among the three types of MS, the number of exacerbations in the secondary progressive (5.9+/-4.6) cohort was significantly higher than that in the relapsing-remitting MS subjects (3.2+/-2.6). Patients with primary progressive MS showed a significantly higher rate of gait disturbance (87.5%) as the initial symptom than those with relapsing-remitting MS (23.8%), and this was thought to be due to the higher incidence of brainstem and spinal cord lesions. Visual disturbance as the initial symptom was frequently noted in those with secondary progressive MS (50.0%), while it was noted only in 29.8% and 12.5% in the relapsing-remitting and primary progressive patients, respectively. Primary progressive MS subjects had a higher propensity to be wheelchair-bound (75.0%) than those suffering from relapsing-remitting MS (1.2%). Increased total protein in the cerebrospinal fluid (CSF) of the secondary progressive cohort was statistically significant compared to the relapsing-remitting cohort. The frequency of oligoclonal IgG bands was rather low in each type of MS (17.1-33.3%). Gadolinium enhancement of plaques on MRI was more frequently present in secondary progressive MS (66.7%) than in either relapsing-remitting MS (32.1%) or primary progressive MS (50.0%). Of note, the opticospinal form was found in only 16.3% of the total MS patients, a proportion less than that in previous reports from southern Japan. CONCLUSION: The present study confirms that while the clinical and laboratory features of the MS patients in the Tokyo metropolitan area are similar to those in Western countries in most regards, features such as proportionally fewer primary and secondary progressive MS patients as well as less oligoclonal IgG bands on CSF analysis are different from those in Western countries.     

Disability in multiple sclerosis is associated with age and inflammatory,metabolic and oxidative/nitrosative stress biomarkers: results of multivariate and machine learning procedures

The aim of this study was to evaluate the immune-inflammatory, metabolic, and nitro-oxidative stress (IM&NO) biomarkers as predictors of disability in multiple sclerosis (MS) patients. A total of 122 patients with MS were included; their disability was evaluated using the Expanded Disability Status Scale (EDSS) and IM&NO biomarkers were evaluated in peripheral blood samples. Patients with EDSS ≥3 were older and showed higher homocysteine, uric acid, advanced oxidized protein products (AOPP) and low-density lipoprotein (LDL)-cholesterol and higher rate of metabolic syndrome (MetS), while high-density lipoprotein (HDL)-cholesterol was lower than in patients with EDSS <3; 84.6% of all patients were correctly classified in these EDSS subgroups. We found that 36.3% of the variance in EDSS score was explained by age, Th17/T regulatory (Treg) and LDL/HDL ratios and homocysteine (all positively related) and body mass index (BMI) (inversely related). After adjusting for MS treatment modalities, the effects of the LDL/HDL and zTh17/Treg ratios, homocysteine and age on disability remained, whilst BMI was no longer significant. Moreover, carbonyl proteins were associated with increased disability. In conclusion, the results showed that an inflammatory Th17 profile coupled with age and increased carbonyl proteins were the most important variables associated with high disability followed at a distance by homocysteine, MetS and LDL/HDL ratio. These data underscore that IM&NO pathways play a key role in increased disability in MS patient and may be possible new targets for the treatment of these patients. Moreover, a panel of these laboratory biomarkers may be used to predict the disability in MS.

     

Late-onset multiple sclerosis

OBJECTIVE: The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. DESIGN: A retrospective chart review. SETTING: The Multiple Sclerosis Center at Sheba Medical Center, Israel. PARTICIPANTS: 640 patients with a definite diagnosis of MS. MEASUREMENTS: Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. RESULTS: Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. CONCLUSIONS: Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.     

Use of low-dose mitozantrone to treat aggressive multiple sclerosis: a single-centre open-label study using patient self-assessment and clinical measures of multiple sclerosis status

BACKGROUND: There is significant evidence supporting the use of mitozantrone in the treatment of multiple sclerosis (MS) but few data on the subtypes of MS that respond or which measures of disease status are most useful. AIMS: To assess the efficacy of low-dose (5 mg/m2 3 monthly) mitozantrone using patient self-assessment questionnaire (SAQ), expanded disability status score (EDSS), multiple sclerosis functional composite score (MSFC), and the fatigue severity scale (FSS). Then, to compare the responses of a subgroup of relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients to treatment, and to assess which measures of MS disease status are the most useful in a study of this type. METHOD: Thirty-one patients with definite (McDonald criteria) active MS were commenced on mitozantrone 5 mg/m2 every 3 months. EDSS, MSFC and FSS data collected before treatment and after 12 months were analysed. The SAQ was administered after at least 12 months of therapy. RESULTS: RRMS patients showed significantly more response to mitozantrone than SPMS patients in terms of MSFC (P = 0.02) and SAQ (P = 0.01). CONCLUSIONS: Low-dose mitozantrone was well tolerated and useful in active RRMS in the short term; however, mitozantrone did not display any useful activity in SPMS patients over this time interval or at the mitozantrone dose used. Patient perception of treatment is a worthwhile outcome measure and the MSFC is the most useful objective measure of MS status change in this type of study.     

Autologous Peripheral Blood Stem Cell Transplantation for Severe Multiple Sclerosis

We describe the results of a clinical trial to evaluate the feasibility and toxicity of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with progressive multiple sclerosis (MS). Fifteen patients (all patients with secondary progressive MS) were enrolled. The median expanded disability status scale (EDSS) score at baseline was 6.0 (range, 4.5-7.5). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. In 9 patients, CD34+ cell selection was performed with a CliniMACS cell selection system, and 6 patients accepted infusion of unmodified peripheral blood stem cells. The modified BEAM (carmustine, teniposide, cytarabine, and melphalan) was the sole conditioning regimen used. The adverse effects included infections, mucositis, transient hepatotoxicity, and diarrhea. Three patients had flares of neurologic deterioration during mobilization, 8 patients had the same manifestation during transplantation, and 2 patients had similar flares within 3 months of transplantation. Six patients experienced continuous neurologic improvement after transplantation, 5 patients experienced neurologic progression, and 4 patients had stabilization of their disease. The confirmed progression-free rate was 63.8% at 49 months. The results of lymphocyte purging were no better than for no purging. Auto-HSCT proved to be safe and beneficial for some MS patients. Further studies are needed to establish the merit of this procedure for MS patients.     

Disability fingerprints: patterns of disability in spinal cord injury and multiple sclerosis differ

BACKGROUND: Models for causation of functional disability differ as to whether different diseases lead to common expressions of disability versus producing unique "disability fingerprints." Multiple sclerosis (MS) and Spinal Cord Injury (SCI) both affect the spinal cord; however, their pathophysiologies differ (progressive vs. nonprogressive; multifocal vs. unifocal). METHODS: Patterns of disability were compared among veterans who reported in a national survey that they had MS (n = 1789) or SCI (n = 6361) as the sole cause of their spinal cord dysfunction. The study used self-reported information on disease duration, physical impairments, and self-care skills to compare the two samples for differences in disability overall and after stratification according to (a) disease duration, and (b) specific physical impairments. RESULTS: Patterns of disability differed significantly among persons with MS compared to SCI (p = .001). Differences in level of disability between the two samples remained statistically significant after stratification on disease duration. There were substantial, statistically significant differences between the two samples in the amount and kinds of physical impairment. However, differences in level of disability between the two conditions remained highly significant after stratifying on number of affected limbs (p = .003), amount of useful movement (p = .001), overall motor impairment (p = .003), amount of sensation (p = .001), impairment in memory and thinking (p = .001), and visual impairment (p = .001). CONCLUSIONS: This study shows differing diseases indeed have unique disability fingerprints, which remain unique after controlling for disease duration and for population-specific differences in physical impairment. These findings point out the need to explain the disablement process more fully.     

Fractional anisotropy of white matter,disability and blood iron parameters in multiple sclerosis

Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n?=?107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS). FA was recorded in 48 white matter tracts in 11 of the female patients with MS and 12 female controls. Results: In patients with high disability scores the mean FA was significantly lower (0.34?±?0.067) than in the control group (0.45?±?0.036; p?=?0.04), while patients with low disability had mean FA values (0.44?±?0.014) similar to controls (p?=?0.5). Positive associations were found between FA and the iron parameters serum iron, ferritin and percentage transferrin saturation (%Tfsat) in all the white matter tracts. For % Tfsat, the associations were highly significant in 14 tracts (p?<?0.01; r-values 0.74–0.84) and p?<?0.001 (r?=?0.83) in the superior fronto occipital fasciculus (LH). In the whole patient group a trend was found towards an inverse association between the EDSS and the %Tfsat (r?=??0.26, p?=?0.05) after excluding male gender and smoking as confounders, suggesting reduced disability in the presence of higher blood iron parameters. Additionally, significant inverse associations between disease duration and haemoglobin (p?=?0.04) as well as %Tfsat (p?=?0.02) suggested that patients with MS may experience a decrease in blood iron concentrations over time.     

Clinical outcome of autologous peripheral blood stem cell transplantation in opticospinal and conventional forms of secondary progressive multiple sclerosis in a Chinese population

To evaluate clinical outcomes of autologous peripheral blood stem cell transplantation (APBCST) between opticospinal multiple sclerosis (OSMS) and conventional multiple sclerosis (CMS) during disease progressive stage in a Chinese population. Thirty-six secondary progressive MS patients, among whom 21 were with OSMS and 15 with CMS, underwent APBSCT and were followed up for an average of 48.92 months (range, 10–91 months). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. Modified BEAM conditioning regimen (Tiniposide, melphalan, carmustin, and cytosine arabinoside) were administered. Outcomes were evaluated using the expanded disability status scale (EDSS). No maintenance treatment was administered if there was no disease progression. No treatment-related mortality occurred. Among the 36 patients, one OSMS patient dropped during the follow-up. Among the 22 relapse-free patients, 20 were with continuous neurological improvement without any relapse events, and two remained in neurologically stable states. Among the 13 relapse patients, seven had experienced of neurological relapse, but with no progression during the follow-up period; and six experienced neurological deterioration after transplantation and needed further immunosuppressant treatment. The confirmed relapse-free survival rate was 62.9% and progression-free survival rate was 83.3% after 91 months according to Kaplan and Meier survival curves. Eleven of the 20 OSMS patients (55%) and two of the 15 CMS patients (13.3%) stayed in disease active group (P = 0.014). For the 20 OSMS patients, the overall EDSS score decreased significantly after transplantation (P = 0.016), while visual functions had no significant improvement (P = 0.716). Progressive OSMS has a higher relapse rate than CMS following APBSCT.     

Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results

The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening 1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of 6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.     

Dehydroepiandrosterone response to the adrenocorticotropin test and the combined dexamethasone and corticotropin-releasing hormone test in patients with multiple sclerosis

Basic and clinical research suggest that disturbed neuroendocrine function may be involved in the pathogenesis and course of autoimmune diseases including multiple sclerosis (MS). Dehydroepiandrosterone (DHEA) in this connection is of particular interest as it appears to have effects on the immune system. Moreover, DHEA levels are decreased in chronic inflammatory diseases. To further investigate the role of DHEA in MS, we administered the adrenocorticotropin (ACTH) stimulation test and the combined dexamethasone and corticotropin-releasing hormone (DEX-CRH) test to 24 patients with active MS (13 women, 11 men; age 39 +/- 2 years, mean +/- SEM; Expanded Disability Status Scale, EDSS score 4.4 +/- 0. 4, mean +/- SEM; 12 with acute relapse, 12 with chronic progression) and to 18 healthy controls matched for age and sex (8 women, 10 men; age 37 +/- 3 years). There were no statistically significant differences in the plasma cortisol response to ACTH between any groups. In the DEX-CRH test, plasma cortisol concentrations showed higher values before (DEX-pretreated) and after CRH stimulation in the MS patients than in the controls (AUC(cortisol) 738.3 +/- 154.5 vs. 295.7 +/- 55.8; p < 0.05), this finding was more pronounced in chronic progressive patients. DHEA concentrations were decreased in MS patients (AUC (DHEA) 14.4 +/- 1.6 vs. 23 +/- 2.4; p < 0.05) and cortisol/DHEA ratios were increased in the patients compared to the controls (p < 0.05). There was a positive correlation between the EDSS score and maximum cortisol/DHEA ratio (r = 0.45; p = 0.031). As with the hypothalamic-pituitary-adrenal axis system, our results suggest a dysfunction in the DHEA secretion in patients with MS.     

Laryngopharyngeal Dysmotility in Multiple Sclerosis

This study investigated the swallowing physiology of 13 patients [age 27-69 years (mean = 45 years)] with multiple sclerosis (MS) who had Kurtzke Extended Disability Status Scale (EDSS) scores ranging from 2 to 9 (mean = 6) and who complained of difficulty swallowing. Videofluoroscopic recordings of the patients' calibrated liquid and paste bolus swallows were analyzed and compared with publi-shed normative data. Results showed that swallowing physiology was disordered in the 13 MS patients with severity level ranging from mild to severe. Eleven patients had primary pharyngeal dysphagia, 1 patient had primary laryngeal dysphagia, and 1 patient had primary oral dysphagia. Laryngeal dysmotility, the predominant anterior pharyngeal segment dysfunction, was evidenced in all 13 patients with MS. They displayed significantly longer-than-normal pharyngeal delay times, shorter-than-normal time intervals from onset of laryngeal excursion to return to rest, and longer-than-normal time intervals between airway closure at the arytenoid to epiglottic base and upper esophageal sphincter opening. Pharyngeal constrictor dysmotility, the predominant posterior pharyngeal segment dysfunction, was observed in 11 of the 13 MS patients. A significant relationship was found between the severity of the MS patients' functional swallowing impairment and posterior pharyngeal segment dysfunction. Material penetrated the supraglottic airway of 9 patients with 1 patient aspirating. A significant relationship was observed between supraglottic penetration and brainstem dysfunction. No significant relationship was found between severity of dysphagia and neurological disability as measured by EDSS scores or neurological impairment as measured by Functional System (FS) scores. Disturbed neuromotor sequencing of laryngeal events and a progression in neuromotor weakening of the pharyngeal constrictors were suggested from the findings.     

Influence of age on the clinical and biological characteristics of systemic scleroderma

PURPOSE: The present study was aimed at assessing the influence of age on clinical and biological features of systemic sclerosis. METHODS: This retrospective study included 151 consecutive patients with systemic sclerosis. The median age at diagnosis was 50.0 years (range: 10-84 years). Patients were divided into two groups according to their age (lower than 50.0 years of age: 73 patients, equal to or above 50 years of age: 78 patients). The following features were compared between the two groups: gender, disease duration, extent of skin sclerosis, Crest syndrome, lung fibrosis, secondary Sj?gren's syndrome, antinuclear, anticentromere, and anti-Scl70 antibodies. RESULTS: The disease duration was significantly higher in patients over 50 years of age (7.1 +/- 6.8 years vs 5.5 +/- 5.0 years, P < 0.05). Crest syndrome, secondary Sj?gren's syndrome and anticentromere antibodies were significantly more common in patients over 50 years of age (17/73 vs 30/78, P < 10(-2); 9/73 vs 20/78, P < 10(-2), and 19/73 vs 31/78, P < 0.05; respectively). Anti-Scl70 antibodies were significantly more common in patients under 50 years of age (17/73 vs 10/78, P < 10(-2)). No significant difference was found in regard to the other features. CONCLUSION: The clinical and biological patterns of systemic sclerosis are different according to the age at disease onset. Crest syndrome including anticentromere antibodies and Sj?gren's syndrome is more common in elderly patients, while anti- Scl-70 antibodies are more common in younger patients. This suggests the involvement of various mechanisms in the pathogenesis of systemic sclerosis, and that these mechanisms may depend on the age.     

CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients

BACKGROUND AND OBJECTIVES: Autologous stem cell transplantation (ASCT) is currently being evaluated as a therapy for patients with multiple sclerosis (MS). We report the results of a phase II trial to evaluate feasibility and toxicity of CD34+ selected ASCT (CD34+/ASCT) and treatment results at one year of follow-up. DESIGN AND METHODS: Patients with advanced secondary progressive (SP) or relapsing-remitting (RR) MS and confirmed worsening of the extended disability status scale (EDSS) in the previous year despite interferon or other immunotherapies were included. Peripheral blood stem cells were obtained by leukaphereses after mobilization with cyclophosphamide (Cy) and granulocyte colony-stimulating factor (G-CSF). CD34+ selection was performed by means of an Isolex 300 or CliniMACS device. BCNU, Cy and antithymocyte globulin (ATG) were administered as conditioning regimen. RESULTS: Fifteen patients (9 SPMS and 6 RRMS) with a median EDSS of 6.0 (4.5-6.5) and a median of 3 (1-7) relapses in the previous year were included. Mobilization was unsuccessful in one patient. During mobilization, one patient had a transient neurologic deterioration. The main complication during ASCT were engraftment syndrome, which developed in three patients, CMV reactivation in one, and neurologic deterioration in two patients coinciding with high-fever related to ATG. Hematologic recovery was fast and complete in all cases. At 12 months, the EDSS had improved in three patients, worsened in two and remained stable in nine. Despite withdrawal of all immunosuppressive therapy only two patients had relapses. Magnetic resonance imaging showed disappearance of enhanced T1 lesions but oligoclonal bands persisted in the cerebrospinal fluid of all evaluated cases. INTERPRETATION AND CONCLUSIONS: CD34+/ASCT using BCNU, Cy and ATG as conditioning regimen has an acceptable toxicity and clearly reduces the progression of MS. Further follow-up is necessary to establish the real impact of this procedure on the long-term evolution of the disease.     

Influence of sex on disease severity in patients with rheumatoid arthritis

OBJECTIVE: To determine whether patient's sex influences the severity of rheumatoid arthritis (RA) in terms of clinical severity or need for treatments. METHODS: This was a retrospective, single-center study. We compared 133 male patients with 133 female patients presenting with RA and matched for disease duration. Data collection included demographic characteristics, pattern of joint involvement, extraarticular manifestations, medical treatment, and joint surgery. Biological measures, HLA genotypes, Larsen radiological scores on radiographs of hands and feet, and Health Assessment Questionnaire (HAQ) results were obtained. RESULTS: Mean disease duration was 7.4 +/- 6.9 years. Concerning clinical pattern of involvement, sicca syndrome was more frequent in women than in men (p = 0.0003). There were no significant differences concerning absence or presence of at least one disease associated gene (HLA-DRB1*01 or *04) in our patients; however, women more often carried 2 disease associated genes (21% vs 11%). No other difference in clinical, biological, or radiological indicators was noted between the 2 populations. Concerning treatment, there was no difference for large joint arthroplasties; female patients underwent significantly more distal joint arthrodesis, 6.7% vs 1.5% (p = 0.03); they were prescribed slightly more disease modifying drugs, 3.33 vs 2.83 (p = 0.04); and showed a trend toward more large joint arthrodesis, 15% vs 7.5% (p = 0.05), and metacarpophalangeal joint arthroplasties, 5.2% vs 0.7% (p = 0.08). CONCLUSION: When patients are matched for RA duration, sex has little effect on the disease pattern and severity, yet women undergo more distal joint surgery.     

Pattern of psoriatic arthritis in an Asian population (Malaysia)

Objective: To profile the pattern of psoriatic arthritis (PsA) and its relationship to disease duration. Methods: Forty‐six consecutive patients with PsA were entered into a cross‐sectional study. Demographic data, disease duration and disability were recorded. Joint involvement was documented at 6 months from onset and at presentation. X‐rays of the sacroiliac (SI) joints, thoracolumbar spine, and hands were taken. HLA B27 typing was done. Results: The male : female ratio was 2.3 : 1, mean age at onset of arthritis was 35.8 years and mean duration of PsA was 4.2 years. Oligoarticular involvement predominated (63%) at onset. Progression from oligoarthritis to polyarthritis occurred largely in the second year; 65.2% reported asymmetrical disease at onset while 50% had asymmetrical disease when disease duration was > 1 year. The frequency of involvement at onset was as follows: sausage toes, metatarsophalangeals (MTPs) and interphalangeals (IPs) in 50% (each), proximal interphelangeals (PIPs) in 47.8%, sausage fingers 34.7% and knees 30%. With mean duration of 4.2 years it was: sausage toe 71.1%, IP 69.5%, PIP and MTP 63%, knees 60.8%, distal interphalangeals (DIPs) 54.3%, sausage finger 52.1%, wrist 47.8%, followed by neck and back pain. Disability related to lower limb functions predominated and occurred early. Forty‐one percent had radiological sacroiliatis/spondylitis and 46% had erosive arthritis in the hands; 10.2% were HLA B27 positive. Conclusion: PsA was progressive, starting predominantly as an asymmetrical oligoarthritis and becoming largely polyarticular within 2 years from onset. Lower limb disability was evident early and erosive changes in hand X‐rays were seen in more than half the patients after 1 year.