Rivastigmine for Cognitive Impairment in Multiple Sclerosis: A Prospective Randomized Open Label study with Blinded End-Point Assessment.

Background and Objective: Nearly 40-65% patients with MS develop cognitive impairment during the disease. There is no treatment clearly effective in improving the cognitive deficits. To evaluate the efficacy and safety of Rivastigmine in cognitively impaired MS patients. Materials and Methods: This was a parallel group randomized open label study with blinded end-point assessment. The patient allocation to treatment and control arm was done by telephonic contact with an independent statistician who used a computer to generate a random sequence of allocation using permuted block randomization (varying block size of 4 and 6) in 1:1 ratio. The outcome assessor was blinded to this allocation. A total of 60 patients were in included in the study (30 in each arm). Primary outcome was improvement in memory functions (using logical memory subset of Wechsler Memory Scale III, India) assessed after 12 weeks. Secondary outcomes included fatigue, depression, and safety. Results: In modified intention to treat analysis (N = 22), treatment arm showed statistically significant improvement in memory function with mean difference of 7.56 [95% CI (0.67,14.46), p 0.032] as compared to control arm. There was no statistically significant difference in outcomes such as fatigue and depression. Vomiting was the most common side effect. No major adverse events were observed in either group. Conclusion: Rivastigmine is safe and effective in improving memory functions in cognitively impaired MS patients. However, our study has a small sample size and tested only a single domain. Larger studies with a validated single comprehensive neuropsychological test are needed.

Assessment of Botulinum Neurotoxin Injection for Dystonic Hand Tremor: A Randomized Clinical Trial.

Importance: There is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum neurotoxin (BoNT) injections on upper-extremity DT. Objective: To assess the effect of BoNT injections on tremor in patients with upper-extremity DT. Design, Setting, and Participants: In this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020. Interventions: Participants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings. Main Outcomes and Measures: The primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later. Results: A total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean [SD] age, 46.0 [18.6] years; 26 [86.7%] male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 [40.0%]; placebo: 4 [28.6%], P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10[kgf/m2]2/Hz-Hz; 95% CI, -0.9 to 0.4 log10[kgf/m2]2/Hz-Hz; P = .45) were similar in both groups. Conclusions and Relevance: In this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects. Trial Registration: Clinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.

Telephonic review for outpatients with epilepsy-A prospective randomized, parallel group study.

PURPOSE: Our objective was to assess how telephonic review of outpatients with stable epilepsy compared with conventional face-to-face clinic management. METHODS: We constructed a randomized parallel group study of suitable patients attending our Epilepsy Clinic and compared telephonic review with conventional clinic visit based management. Primary outcomes were the percentage of patients with breakthrough seizures and total number of breakthrough seizures. We also compared cost, patient satisfaction and numbers defaulting. RESULTS: A total of 465 patients were randomized and 429 were included in the final analysis. There was no significant difference in breakthrough seizures between the two groups. Mean time spent in the consultation was 10min in the telephone group (FT) and 22h in the face-to-face group (FC) and cost was INR 865 more expensive on an average in the FC group. Satisfaction was over 90% in the FT group. Significantly more people in the FC group were lost to follow-up. CONCLUSION: This study provides Class I evidence that the number of stable epilepsy patients who have breakthrough seizures and the total number of breakthrough seizures remain the same irrespective of whether patients are reviewed telephonically or face-to-face in the clinic. Clinicians managing epilepsy patients should consider using telephonic review for selected patients. Telephonic reviews have the potential of effectively reducing the secondary treatment gap in millions of patients who do not have easy access to doctors.

Prescription of "ineffective neuroprotective" drugs to stroke patients: a cross sectional study in North Indian population.

In a developing country, where patient access to tertiary care is limited and most patients have to pay out of pocket, it is imperative for the physicians to practice evidence-based medicine. Reports on prescription details and surveys are not available. The aim of this study is to describe the prescribing patterns for various medications used in the treatment of stroke among the first contact physicians in North India; to estimate the proportion of patients being prescribed the non-recommended drugs and to determine any relationship between the economic status of the patient and the prescription pattern. Details of economic status, education level, type of stroke, type of hospital, qualification of treating physician and the number and nature of medications were noted from the prescriptions and patients. Two hundred and sixteen patients with ischemic stroke (71.3% males, average age 51.5 years) were included. Among poor patients, N = (36.8%) received any of the neuroprotective drugs including citicoline 19 (27.5%), piracetam 11(15.9%) and edaravone 2(2.9%). Both specialist and private hospitals are associated with higher prescription of "ineffective neuroprotective" drugs in both poor and rich patients. Reasons for overprescribing neuroprotective medications need to be studied and remedial measures need to be taken to practice evidence-based medicine.

Psychosocial impact of epilepsy in women of childbearing age in India.

The aim was to evaluate comprehensively the psychosocial impact of epilepsy in women between 15-40 years of age with epilepsy, compared to those with migraine and healthy, pregnant women. One hundred women with epilepsy, 50 with migraine and 100 healthy, pregnant women were enrolled over a two-year period. The three groups were assessed using questionnaires for quality of life (QOL), coping strategies and caregiver burden. The influence of demographic and seizure variables on these psychosocial outcomes were also assessed.It was found that quality of life was least, and the burden experienced by the caregiver was significantly more in patients with epilepsy (p < 0.001). Women with epilepsy relied more on religion/faith as a coping method (p = 0.021), and less on problem solving strategies (p < 0.001) when compared to those with migraine. When compared to healthy, pregnant women, they more frequently employed religious methods of coping and denial (p < 0.001), with significantly less use of problem solving techniques, acceptance, and positive and negative distraction(p < 0.001). Less frequent seizures, better education and remission sustained for at least six months, were associated with better QOL. Educational status, frequency of seizures and time elapsed since last seizure emerged as significant determinants of coping behaviour. Low educational status and monthly income of the family contributed significantly to caregiver burden.This study helped to identify the different areas of psychosocial impairment in patients with epilepsy, as well as the contributing factors. Women with epilepsy rarely used constructive coping strategies, and this was found to contribute to their poor psychosocial status and adjustment within the family and society at large.