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 >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 > 30% deterioration in 3TUG time versus 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). 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.

Parkinson's disease-related fatigue: A case definition and recommendations for clinical research.

Fatigue is one of the most common and disabling symptoms in Parkinson's disease (PD). Since fatigue was first described as a common feature of PD 20 years ago, little progress has been made in understanding its causes or treatment. Importantly, PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. In response, the Parkinson Disease Foundation and ProjectSpark assembled an international team of experts to create recommendations for clinical research to advance this field. The working group identified several areas in which shared standards would improve research quality and foster progress including terminology, diagnostic criteria, and measurement. Terminology needs to (1) clearly distinguish fatigue from related phenomena (eg, sleepiness, apathy, depression); (2) differentiate subjective fatigue complaints from objective performance fatigability; and (3) specify domains affected by fatigue and causal factors. We propose diagnostic criteria for PD-related fatigue to guide participant selection for clinical trials and add rigor to mechanistic studies. Recommendations are made for measurement of subjective fatigue complaints, performance fatigability, and neurophysiologic changes. We also suggest areas in which future research is needed to address methodological issues and validate or optimize current practices. Many limitations in current PD-related fatigue research may be addressed by improving methodological standards, many of which are already being successfully applied in clinical fatigue research in other medical conditions (eg, cancer, multiple sclerosis). © 2016 International Parkinson and Movement Disorder Society.

Management of amyotrophic lateral sclerosis (ALS) by the family nurse practitioner: a timeline for anticipated referrals.

PURPOSE: This article reviews characteristics of amyotrophic lateral sclerosis (ALS) and appropriate timing of referrals by the nurse practitioner (NP). DATA SOURCES: Selected research and clinical articles. CONCLUSION: Management of patients with ALS by the NP requires anticipation of needed referrals based on symptom assessment and knowledge of the common timeline of ALS progression. Close collaboration with specialists such as neurologists, pulmonologists, and a palliative care team provides patients and families with much needed support and improves outcomes. IMPLICATIONS FOR PRACTICE: Anticipating and initiating appropriate and timely referrals for patients with ALS may improve quality of life for patients with this devastating condition.

Concentric Needle Quantitative EMG of Pubovisceralis Muscle Group: Normative Data from Asymptomatic Nulliparous Women.

OBJECTIVES: The muscles of the pelvic floor closest to the vaginal opening are subject to the greatest degree of stretch during vaginal childbirth. We aim to define normative quantitative EMG (QEMG) parameters for the pubovisceralis (PV) muscle in nulliparous women, and compare them to the external anal sphincter (EAS). METHODS: In 31 asymptomatic nulliparous women, concentric Needle EMG of the PV and the EAS was performed. Multi-motor unit action potential (Multi-MUAP) and interference pattern (IP) algorithms were utilized to obtain QEMG parameters. We used paired t-tests to compare PV and EAS parameters. RESULTS: The motor units for the PV were of greater duration (p < 0.002) and had more turns (p = 0.03) than the paired motor units in the EAS. The EAS demonstrated more turns/second (p = 0.02), greater activity (p = 0.01), and more short segments (p = 0.009) than the PV. CONCLUSIONS: The PV has longer and more complex motor units than the EAS. This knowledge continues to improve our ability to detect neuropathic changes in this vulnerable muscle area following childbirth or in women with pelvic floor dysfunction. In addition, the PV muscle group appears less responsive to requests for increased neuromuscular activity than the EAS. This needs to be further evaluated, as it may be associated with understanding which portion of the muscle functionally shortens to maintain the closure of the levator hiatus.

Correlates of quality of life in ALS: Lessons from the minocycline study.

Improving quality of life (QoL) is a major goal in ALS palliative care. Previous studies performed on the general ALS population showed no relationship between QoL and disease progression. ALS subjects participating in clinical trials may differ from those in the general ALS population. We explored the relationship between QoL and disease progression in 412 subjects enrolled in a minocycline trial. We examined correlations between Single Item McGill Quality of Life Scale (MQoL-SIS) score and disease duration, ALS Functional Rating Scale Revised (ALSFRS-R) score, FVC, and survival rate. We also analyzed how NIV and PEG affect QoL. Within subjects, MQoL-SIS scores correlated with ALSFRS-R and FVC (p<0.001). MQoL-SIS declined over time (p<0.001) and correlated with the decline of ALSFRS-R (p<0.001). MQoL-SIS tended to improve after initiation of NIV (p=0.07). There was a significant reduction in the rate of MQoL-SIS decline (p<0.001) after initiation of PEG. Subjects with slower QoL decline survived seven months longer than those with faster QoL decline (p<0.01). Our study demonstrated that QoL does decline with advancing ALS in subjects who participated in a minocycline trial, that the slope of QoL predicts survival, and that both NIV and PEG have beneficial impacts on QoL.

A randomized comparison of thalamic stimulation and lesion on self-paced finger movement in essential tremor.

Deep brain stimulation (DBS) and ablation (thalamotomy) of the motor thalamus reduce tremor and improve function of the contralateral hand in patients with essential tremor (ET). Neuroimaging and electrophysiological evidence suggest that unlike a focal lesion, high frequency stimulation affects widespread neural networks that include those involved in motor timing. The purpose of this pilot study was to compare the effects of thalamic stimulation and lesion on the timing of simple, self-paced finger movements in patients with ET. Twenty-one subjects with advanced ET were randomized to unilateral thalamotomy or DBS. Nine healthy controls were also enrolled. Index finger tapping was performed on both hands before and 6 months after surgery. Prior to surgery, timing of simple, repetitive index finger taps was abnormal in both TH and DBS subjects on the contralateral hand. After surgery, regularity was improved by both stimulation and thalamotomy with significantly more improvement in the TH group. On the ipsilateral (non-targeted) hand, timing of index finger taps was improved by stimulation. These results suggest that temporal processing is differentially affected by stimulating and lesioning thalamocortical fibers. That timing regularity is improved ipsilateral to the stimulated thalamus provides evidence that DBS influences a widespread neural network involved in timing of simple repetitive movements.