Muscle Synergy-Based Functional Electrical Stimulation Reduces Muscular Fatigue in Post-Stroke Patients: A Systematic Comparison.

Muscle synergy-based functional electrical stimulation had improved movement kinematics instantly and in long-term use in post-stroke patients. However, the therapeutic benefits and efficacy of muscle synergy-based functional electrical stimulation patterns over traditional stimulation patterns need exploration. This paper presents the therapeutic benefits of muscle synergy-based functional electrical stimulation compared to traditional stimulation patterns from the perspective of muscular fatigue and kinematic performance produced. Three stimulation waveforms/envelopes: customized rectangular, trapezoidal, and muscle synergy-based FES patterns were administered on six healthy and six post-stroke patients to achieve full elbow flexion. The muscular fatigue was measured through evoked-electromyography, and the kinematic outcome was measured through angular displacement during elbow flexion. The time domain (peak-to-peak amplitude, mean absolute value, root-mean-square) and frequency domain (mean frequency, median frequency) myoelectric indices of fatigue were calculated from evoked-electromyography. Myoelectric indices of fatigue and peak angular displacements of elbow joint were compared across waveforms. The presented study found that the muscle synergy-based stimulation pattern sustained the kinematic output for longer durations and induced less muscular fatigue followed by trapezoidal and customized rectangular patterns in healthy and post-stroke participants. These findings imply that the therapeutic effect of muscle synergy-based functional electrical stimulation stems from not only being biomimetic but also due to it being efficient in inducing less fatigue. The slope of current injection was a crucial factor in determining the performance of muscle synergy-based FES waveforms. The presented research methodology and outcomes would help researchers and physiotherapists in choosing effective stimulation patterns for maximizing post-stroke rehabilitation benefits. Note: FES waveform/ pattern/ stimulation pattern all refers to FES envelop in this paper.

Importance of high-quality evidence regarding the use of Bacopa monnieri in dementia.

Background: Bacopa monnieri (BM), a commonly used herb, has shown neuroprotective effects in animal and in vitro studies; but human studies on patients with Alzheimer's Disease (AD) have been inconclusive. Further high-quality trials are required to conclusively state the utility of BM in AD and other neurodegenerative dementias. Methods: In the present study, we did a narrative review of the current challenges in designing clinical trials of BM in dementia and their evidence-based recommendations. Results: Many facets of the BM trials need improvement, especially effect size and sample size estimation. Current assessment and outcomes measures need a more holistic approach and newer scales for diagnosing and monitoring prodromal AD. The stringent guidelines in CONSORT and STROBE are often considered difficult to implement for clinical trials in ayurvedic medications like BM. However, adherence to these guidelines will undoubtedly improve the quality of evidence and go a long way in assessing whether BM is efficacious in treating AD/prodromal AD patients and other neurodegenerative dementias. Conclusion: Future studies on BM should implement more randomized controlled trials (RCTs) with an appropriate sample size of accurately diagnosed AD/prodromal AD patients, administering a recommended dosage of BM and for a pre-specified time calculated to achieve adequate power for the study. Researchers should also develop and validate more sensitive cognitive scales, especially for prodromal AD. BM should be evaluated in accordance with the same rigorous standards as conventional drugs to generate the best quality evidence.

Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study.

OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). PATIENTS AND METHODS: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). RESULTS: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. CONCLUSION: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.