Clinical benefits of interferon beta-1a in relapsing-remitting MS: a phase IV study.

OBJECTIVE: To evaluate the efficacy and safety of IFNbeta-1a (Avonex, Biogen, Inc., Cambridge, MA, USA) in patients with relapsing-remitting multiple sclerosis (MS). METHODS: In this multicenter, open-label, prospective clinical trial, 96 patients with relapsing-remitting MS received IFNbeta-1a 30 mcg intramuscularly once weekly for 2 years. Outcome variables included: change from baseline in mean number of exacerbations, proportion of exacerbation-free patients, and mean Expanded Disability Status Scale (EDSS) scores at Years 1 and 2. RESULTS: IFNbeta-1a significantly (P < 0.0001) reduced exacerbation rate at Years 1 and 2 of treatment. The percentage of exacerbation-free patients was 53% during Year 1 and 33% during Year 2. Mean EDSS scores were 2.96 +/- 1.26 at baseline, 2.89 +/- 1.42 at Year 1, and 3.00 +/- 1.62 at Year 2 (P = 0.116). EDSS scores improved in 35.4%, remained stable in 28.1%, and worsened in 36.5% of patients. IFNbeta-1a treatment was well tolerated. CONCLUSION: This study confirms and extends the beneficial clinical profile for IFNbeta-1a in relapsing MS.

Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients.

OBJECTIVES: We study the power of IgG synthesis value as a marker of disease activity in multiple sclerosis (MS). MATERIAL AND METHODS: Link index was calculated in 202 MS patients. Time between first, second and third attack and progression index (PI) were compared in patient with normal (NLI) high (HL) or very high Link index (VHLI). RESULTS: Secondary progressive (SP) patients had a higher LI than relapsing-remitting (RR) and primary progressive (PP) courses (1.10 +/- 0.5 for SP vs 0.86 +/- 0.5 for RR and 0.81 +/- 0.5 for PP, P=0.01 and 0.03, respectively). Having a HLI in MS RR and SP patients has no time effect in the development of the second and third attack. PI was higher in patients with VHIL (0.67 +/- 0.7) vs patients with NLI (0.42 +/- 0.4, P=0.008) and with HLI (0.39 +/- 0.3, P=0.001). CONCLUSIONS: This study confirmed that LI is a good marker of subsequent progression of MS.

Serum endothelial adhesion molecules levels correlate with lesion burden in multiple sclerosis patients treated with interferon beta-1b.

The levels of serum-soluble intracellular adhesion molecule-1 and soluble endothelial-leukocyte adhesion molecule-1, and the Gadolinium-enhanced T1-weighted MRI were studied in a group of patients with relapsing-remitting multiple sclerosis treated with interferon beta-1b and compared to a non-treated control group. The levels of serum-soluble intracellular adhesion molecule-1 and soluble endothelial-leukocyte adhesion molecule-1 increased, after three months treatment, as compared to baseline and the non-treated MS patients. A significant correlation was found in the treated group between serum-soluble endothelial-leukocyte adhesion molecule-1 and the lesion area in the Gadolinium-enhancing (T2 weighted scan) MRI.

[Clinical features of familial multiple sclerosis in Spain]. / Características clínicas de la esclerosis múltiple familiar en España.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system (CNS) with a clear proved genetic susceptibility. The real frequency and clinical features of familial MS is although not well established in Spain. OBJECTIVE: We studied the clinical and CSF features of familial MS (FMS) patients in comparison with the rest of our patients. PATIENTS AND METHODS: We reviewed 308 definite MS patients looking for patients with other familial members with MS. We analyzed clinical characteristics (age, age at onset, sex, evolution time, evolution course, symptoms at onset, disability measured by EDSS scale) and IgG synthesis measured by Tibbling-Link index. RESULTS: We found 23 patients (10 men and 13 women) in 18 independent families with at least other family member diagnosed of definite MS (7.47% of our total MS population). Age and age at onset were no different from non FMS cases. The clinical course was relapsing-remitting in 21 out of 23 FMS cases and secondary progressive in two. No primary progressive cases were found among FMS. At onset the symptom most frequently found in FMS was optic neuritis. Mean EDSS score was lower in FMS cases in comparison with the rest of cases. Link index was increase in 93.7% of patients with FMS. CONCLUSION: In comparison with non familiar forms FMS patients in Spain, present more often remitting courses, are less disabled, optical neuritis is more frequently seen as onset symptom and IgG synthesis is more often increased.

[Multiple progressive occlusions of intracranial arteries]. / Oclusiones progresivas múltiples de arterias intracraneales.

OBJECTIVES: We present a case of multiple progressive occlusions of intracranial arteries, a variety of Taveras' syndrome, without smoke spirals, which may be confused with other multifocal disorders. PATIENT: A 30 year old woman was admitted to hospital with a clinical picture of fluctuating paresia of her left limbs, blurred vision and urgency of micturition which partially recovered. On examination there was paresia of the left arm, generalized increased reflexes and facial asymmetry. RESULTS: On MRI there were areas of marked hyperintensity at T2. Some of these took up gadolinium at T1 and had a serpiginous pattern, compatible with vasculopathy. On angiography, stenosis and filling defect were seen in the left carotid artery. The anterior cerebral and left Sylvian arteries were filled by the vertebrobasilar system via the posterior communicating artery and an anomalous trigeminal artery. CONCLUSIONS: The clinical picture of multiple progressive occlusions of intracranial arteries is a variety of moya-moya disease, without the typical smoke spirals, which may lead to confusion with clinical pictures of arteritis and demyelinating disorders if angiography is not done, since this is essential for diagnosis.

[Evolution and adverse effects in patients with remittent-recurrent multiple sclerosis treated with interferon beta 1b. The influence of patient's weight and height]. / Evolución y efectos adversos en pacientes con esclerosis múltiple remitente-recidivante tratados con interferón beta 1b. Influencia del peso y la talla de los enfermos.

BACKGROUND: The aim of the present study was to determine whether the adverse effects (AE) of interferon beta 1b (IFNb-1b) are related to patient weight, height and body surface area. Moreover, whether the basal incapacity and/or some of these AE may be related to the evolutive prognosis were also studied. METHODS: Twenty-nine females and 14 males with remittent-recurrent multiple sclerosis treated with IFNb-1b were studied. The clinical data and the AE, were compared with the number of outbreaks and the progression of incapacity over the first year of treatment in patients with high weight, height and body surface area with respect to those under the mean. RESULTS: Although the presence of fever was similar in the two groups during the first month (8/19 in the high weight patients and 11/24 in the low weight group), in the following months, overall, the low weight patients continued to present fever. Fever during the first month was associated with a lower number of outbreaks at one year of evolution (0.04 +/- 0.1, n = 19 vs 0.30 +/- 0.5, n = 24; p = 0.04). Furthermore, the patients with lesser incapacity presented a better evolution than those with more incapacity, particularly at 2 years (0.21 +/- 1.3 vs 1.36 +/- 0.9; p = 0.05). CONCLUSIONS: During the first month of treatment fever is very frequent in all the patients regardless of weight and fever was correlated with a lower number of outbreaks at one year of evolution. From the third month fever was less frequent in the lower weight patients group.

[Changes in lymphocyte subsets s and treatment with beta interferon in active multiple sclerosis]. / Evolución de subpoblaciones linfocitarias y tratamiento con interferón beta en la esclerosis múltiple activa.

INTRODUCTION: We report that interferon beta decreases CD8 T cells percentage and increases CD4/CD8 cell's rate in vivo in Multiple Sclerosis (MS) patients. PATIENTS AND METHODS: We studied 40 patients (22 women and 18 men) with clinically definite active MS who received IFN beta. Twenty-six were treated with nIFN (9 MU/week) and 14 with rIFN (28 MU/week). All patients except two with secondary progressive forms presented relapsing remitting courses. Mean age and mean age at onset were 36.5 +/- 9 and 27.8 +/- 7 years respectively. Mean EDSS score was 2.96 +/- 1.8. Patients were reviewed at four weeks and every eight weeks and periodical studies of immunity were performed. T cell subpopulations (CD3, CD4, CD8 and NK) were studied byflow cytometry. RESULTS: The evolution of CD8 T cell percentage showed a statistically significant decrease in all blood samples after 20 weeks of treatment with rIFN (24.3 +/- 8 vs 34.7 +/- 5 in the control group) and after 36 weeks for nIFN beta group (25.7 +/- 6 vs 33.0 +/- 4 in the control group). No changes were detected in CD4 T cell subset. The evolution of CD4/CD8 T cell rate showed an increase over the cut-off (2.200) in all blood samples after 20 weeks of treatment with rIFN (2.302 +/- 1.12, 2.332 +/- 0.99 and 2.488 +/- 1.61 for 20, 28 and 36 weeks respectively) and after 52 weeks for nIFN beta group (2.128 +/- 1.07, 2.346 +/- 1.09 and 3.168 +/- 3.87 for 52, 60 and 68 weeks respectively). CONCLUSIONS: Both nIFN and rIFN beta are able in vivo to decrease CD8 percentage of T cells and increase CD4/CD8+ T cell rate. The increase in the rate is produced earlier in the rIFN treated group.

[Myelographic diagnosis of an epidural arterio-venous fistula]. / Diagnóstico mielográfico de una fistula arteriovenosa epidural.

INTRODUCTION: Epidural arterio-venous fistulae are a little known clinical condition. They are probably commoner than is thought, since diagnosis and angiographic demonstration are difficult. CLINICAL CASE: We present the case of a 49 year old man with the clinical features of chronic myelo-radiculopathy with episodes of intermittent medullary claudication. This shows the use of myelography, which in certain cases allows clear detection of vascular structures which might otherwise pass unnoticed. CONCLUSIONS: One should think of this condition when compatible features are found and there is no other diagnosis, since if confirmed by myelography and/or magnetic resonance prior to angiographic study, it may benefit from embolization, which is an effective treatment for this.