3,4-Diaminopyridine Base Effectively Treats the Weakness of Lambert-Eaton Myasthenia

Introduction: 3,4-diaminopyridine has been used to treat Lambert Eaton myasthenia (LEM) for thirty years despite the lack of conclusive evidence of efficacy. Methods: We conducted a randomized double-blind placebo-controlled withdrawal study in LEM patients who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in Triple Timed Up-and-Go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM–related weakness (W-SAS). Results: 32 participants were randomized to continuous 3,4-DAP or placebo. None of the 14 receiving continuous 3,4-DAP had >30% deterioration in 3TUG time vs 72% of the 18 who tapered to placebo (p<0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (p<0.0001). Need for rescue and adverse events were more common in the placebo group. Discussion: This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM

Relationship between Ischemic Stroke and Pulse Rate Variability as a Surrogate of Heart Rate Variability

Autonomic reflex ascertains cardiovascular homeostasis during standing. Impaired autonomic reflex could lead to dizziness and falls while standing; this is prevalent in stroke survivors. Pulse rate variability (PRV) has been utilized in the literature in lieu of heart rate variability (HRV) for ambulatory and portable monitoring of autonomic reflex predominantly in young, healthy individuals. Here, we compared the PRV with gold standard HRV for monitoring autonomic reflex in ischemic stroke survivors. Continuous blood pressure and electrocardiography were acquired from ischemic stroke survivors (64 ± 1 years) and age-matched controls (65 ± 2 years) during a 10-minute sit-to-stand test. Beat-by-beat heart period (represented by RR and peak-to-peak (PP) intervals), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse arrival time (PAT), an indicator of arterial stiffness, were derived. Time and frequency domain HRV (from RR intervals) and PRV (from PP intervals) metrics were extracted. PAT was lower (248 ± 7 ms vs. 270 ± 8 ms, p < 0.05) suggesting higher arterial stiffness in stroke survivors compared to controls during standing. Further, compared to controls, the agreement between HRV and PRV was impaired in stroke survivors while standing. The study outcomes suggest that caution should be exercised when considering PRV as a surrogate of HRV for monitoring autonomic cardiovascular control while standing in stroke survivors.Applied Science, Faculty ofNon UBCElectrical and Computer Engineering, Department ofReviewedFacult

3,4‐diaminopyridine base effectively treats the weakness of Lambert‐Eaton myasthenia

INTRODUCTION:3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. METHODS:We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was &gt;30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). RESULTS:Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had &gt; 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P &lt; 0.0001). W-SAS similarly demonstrated an advantage for continuous treatment over placebo (P &lt; 0.0001). Requirement for rescue and adverse events were more common in the placebo group. DISCUSSION:This trial provides significant evidence of efficacy of 3,4-DAP in the maintenance of strength in LEM. Muscle Nerve 57: 561-568, 2018