Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study.

INTRODUCTION: Rituximab is considered as a potential therapeutic option in relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in MS. PATIENTS AND METHODS: Observational study of effectiveness (clinical and radiological) and safety of rituximab in RRMS and PMS. RESULTS: A total of 90 rituximab-treated patients were collected: 31 RRMS and 59 PMS All patients had an active disease despite standard treatment. The annualized relapse rate (ARR) the year before rituximab was 0.86, 53.3% of patients had gadolinium enhanced lesion, and mean Expanded Disability Status Scale (EDSS) had increased from 4.2 to 4.9. During treatment, the ARR was reduced an 88.4% (p < 0.001). A significant decrease of EDSS to 4.6 was observed (p = 0.01) after 1 year of treatment, which remained stable during the second year in both groups. There was no evidence of disease activity in 70% of total sample, 74.2% of RRMS, and 67% of the PMS patients. Infusion-related symptoms were the most prevalent side effect (18.8%) and most were mild. Three thrombotic events were detected. CONCLUSION: Rituximab could be an effective and safe treatment in aggressive RRMS. Some selected PMS patients could also benefit from this treatment.

Causal role for the subthalamic nucleus in interrupting behavior.

Stopping or pausing in response to threats, conflicting information, or surprise is fundamental to behavior. Evidence across species has shown that the subthalamic nucleus (STN) is activated by scenarios involving stopping or pausing, yet evidence that the STN causally implements stops or pauses is lacking. Here we used optogenetics to activate or inhibit mouse STN to test its putative causal role. We first demonstrated that optogenetic stimulation of the STN excited its major projection targets. Next we showed that brief activation of STN projection neurons was sufficient to interrupt or pause a self-initiated bout of licking. Finally, we developed an assay in which surprise was used to interrupt licking, and showed that STN inhibition reduced the disruptive effect of surprise. Thus STN activation interrupts behavior, and blocking the STN blunts the interruptive effect of surprise. These results provide strong evidence that the STN is both necessary and sufficient for such forms of behavioral response suppression.

Early diffuse demyelinating lesion in the cervical spinal cord predicts a worse prognosis in relapsing-remitting multiple sclerosis.

OBJECTIVE: To study the long-term outcome and persistence of two patterns of cervical spinal cord abnormality in early relapsing-remitting multiple sclerosis (RRMS). METHODS: RRMS patients with a spinal cord MRI performed during the first 3 years of the disease, a control MRI 5 years later and who have been followed up at least 10 years were included. Patients were grouped according the T2 spinal cord MRI into: (A) nodular pattern, if one or more focal lesions were present; and (B) diffuse pattern, defined as a poorly demarcated high signal area. The end point was defined as the time to reach an Expanded Disability Status Score (EDSS) of 4.0. RESULTS: Twenty-five patients were included; 12 in group A and 13 in group B. Three patients in group A and 9 in group B reached EDSS 4, in a mean time of 11 years in group A and 7 years in group B (log rank 10.3, p = 0.001). Multivariate Cox regression analysis assessing the risk of EDSS 4.0 including sex, age, number of relapses in the first 2 years, number of T2 brain lesions and spinal cord pattern showed higher risk for the diffuse pattern (hazard ratio 7.2, 95% confidence interval 1.4-36.4). Control MRI showed the persistence of the diffuse pattern in all patients, and the development of diffuse pattern in two patients with basal nodular lesions. CONCLUSIONS: The diffuse abnormality in cervical spinal cord at the beginning of the disease is persistent and predicts a worse prognosis in RRMS patients.

[Seronegative myasthenia gravis associated with other autoimmune diseases]. / Miastenia gravis seronegativa asociada a otras enfermedades autoinmunes.

INTRODUCTION: The presence of muscle-specific receptor tyrosine kinase (MuSK) defines a subset of patients with generalized myasthenia gravis. The diagnosis of this disease, due to its clinical distribution and negativity of the acetylcholine receptor (AchR) antibodies, is mo re complicated, especially when linked to other autoimmune diseases. CASE REPORT: A 41 year woman with 3 month long symptoms consisting in diplopia, dysarthria and gait instability. On examination, only mild paresis of the right external rectus without fatigability. The complementary tests performed were evoked potentials were normal including multimodal except for the brain magnetic resonance imaging that detected six-eight hyperintense periventricular nodular lesions in both semioval centers, with impairment of corona radiata and corpus callosum without contrast uptake. Given these findings, she was diagnosed of demyelinating disease and treated with megadoses of methylprednisolone for 5 days with mild clinical improvement. At one month, her condition deteriorated, presenting dysphagia and respiratory failure. The neurophysiological study was extended, and very pathological Jitter was detected in the frontal muscle. Despite the negative AchR antibodies, treatment was initiated with pyridostigmine bromide with poor response, admission to the intensive care unit and plasmapheresis due to a new respiratory episode being required. The torpid course and positive outcome of the MuSK antibodies have confirmed the diagnosis. CONCLUSIONS: The detection of these antibodies and performance of neurophysiological tests in clinically deficient muscles are required for the diagnosis of these clinical forms, especially when the neuroimaging-based pathological findings do not justify the clinical course of the patient.

Veterinary technicians: an important asset to the team.

This report is a brief look at the educational background and expertise of the veterinary technician. The article also looks at the relationship between the veterinary technician and other members of the veterinary health care team with emphasis on the benefits of effectively using the veterinary technician's talents.

Consumption of carbonated and noncarbonated sports drinks during prolonged treadmill exercise in the heat.

These studies were done to determine the effect of carbonation and carbohydrate content on either gastric emptying or ad libitum drinking during treadmill exercise in the heat. Four test drinks were used: a 6% carbohydrate, noncarbonated; a 6% carbohydrate, carbonated; a 10% carbohydrate, noncarbonated; and a 10% carbohydrate, carbonated drink. For gastric emptying studies, subjects completed four 1-hr treadmill runs in the heat. They were given 400 mL of test drink at 0 min and 200 mL at 15, 30, and 45 min of exercise. For ad libitum drinking studies, subjects completed four 2-hr treadmill runs in the heat. Gastric residual volumes were similar during the four 1-hr runs. During the 2-hr runs, ad libitum drinking of the four beverages was also similar. Mean values for sweat rate, percentage of body weight lost, and percentage of fluid replaced by ad libitum drinking were similar for the four trials. Similar changes in heart rate, rectal temperature, and ratings of perceived exertion were also observed during the four 2-hr treadmill runs. We conclude that the presence of carbonation in a carbohydrate drink did not have a significant effect on either gastric emptying or ad libitum drinking.