Nusinersen induces detectable changes in compound motor action potential response in spinal muscular atrophy type 1 patients with severe impairment of motor function.

BACKGROUND: Most long-term affected spinal muscular atrophy (SMA) type 1 patients have severe impairment of motor function and are dependent on mechanical ventilation with tracheostomy. The efficacy and safety of nusinersen in these patients have not been established. METHODS: We retrospectively evaluated the efficacy of intrathecal nusinersen treatment in patients with SMA type 1 who continued treatment for at least 12 months. There were three patients enrolled in our study (3, 4 and 16 years of age) who had severe impairment of gross motor function without head control or the ability to roll over. All three needed mechanical ventilation with tracheostomy and tube feeding. Motor function was assessed using the Children s Hospital of Philadelphia infant test of neuromuscular disorders (CHOP-INTEND) and the caregivers' evaluations. Concurrently, we examined nerve conduction longitudinally and compared compound motor action potential (CMAP) amplitudes. RESULTS: All patients continued nusinersen administration without significant adverse events for more than three years. While CHOP-INTEND scores did not remarkably increase, according to the caregivers, all three patients had improved finger or facial muscle movements that enabled them to make their intentions understood. Some CMAPs before treatment were not identified but became traces after nusinersen administration. CONCLUSIONS: The improvement in motor function that leads to smoother communication could be a basis for continuing nusinersen treatment. Currently available motor function scorings are not efficient for assessing therapeutic interventions in SMA patients with medical care complexity. Longitudinal nerve conduction studies could be an objective indicator.

Factors Affecting Transcranial Motor-Evoked Potential Measurements Using Single-Train Stimulation with an Increased Number of Pulses during Adolescent Scoliosis Surgery: A Prospective Observational Study.

Measurement of transcranial motor-evoked potentials (TcMEPs) during scoliosis surgery helps detect postoperative new neurological defects. However, TcMEP interpretation is difficult owing to the influence of intraoperative physiological, pharmacological, and time-related factors as well as stimulation conditions. In this study, we aimed to investigate the effect of the abovementioned factors on TcMEP amplitude using single-train stimulation with an increased number of pulses (STS-INP) during adolescent scoliosis surgery; moreover, we evaluated the complications of TcMEP measurement. We included 50 patients and 706 TcMEP measurements. A total of 1412 TcMEP waveforms were analyzed, each on the bilateral abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles. We estimated the mean difference (95% confidence interval (CI)) and predicted mean difference (95% CI) evaluated using the interquartile range of each factor, based on a mixed-effect model with random intercepts for TcMEP amplitude. The predicted mean differences in TcMEP amplitude were clinically small compared with the actual TcMEP amplitude, suggesting that each factor had a limited effect on TcMEP amplitude. No intraoperative bite injuries or seizures were observed. Using STS-INP during adolescent scoliosis surgery may enable accurate measurement of TcMEP amplitude with neither complications nor the influence of various intraoperative factors.

Comprehensive assessment of impaired peripheral and coronary artery endothelial functions in smokers using brachial artery ultrasound and oxygen-15-labeled water PET.

BACKGROUND: Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. METHODS AND RESULTS: Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). CONCLUSIONS: Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries.

Accurate quantitative measurements of brachial artery cross-sectional vascular area and vascular volume elastic modulus using automated oscillometric measurements: comparison with brachial artery ultrasound.

Increasing vascular diameter and attenuated vascular elasticity may be reliable markers for atherosclerotic risk assessment. However, previous measurements have been complex, operator-dependent or invasive. Recently, we developed a new automated oscillometric method to measure a brachial artery's estimated area (eA) and volume elastic modulus (V(E)). The aim of this study was to investigate the reliability of new automated oscillometric measurement of eA and V(E). Rest eA and V(E) were measured using the recently developed automated detector with the oscillometric method. eA was estimated using pressure/volume curves and V(E) was defined as follows (V(E)=Δ pressure/ (100 × Δ area/area) mm Hg/%). Sixteen volunteers (age 35.2±13.1 years) underwent the oscillometric measurements and brachial ultrasound at rest and under nitroglycerin (NTG) administration. Oscillometric measurement was performed twice on different days. The rest eA correlated with ultrasound-measured brachial artery area (r=0.77, P<0.001). Rest eA and VE measurement showed good reproducibility (eA: intraclass correlation coefficient (ICC)=0.88, V(E): ICC=0.78). Under NTG stress, eA was significantly increased (12.3±3.0 vs. 17.1±4.6 mm(2), P<0.001), and this was similar to the case with ultrasound evaluation (4.46±0.72 vs. 4.73±0.75 mm, P<0.001). V(E) was also decreased (0.81±0.16 vs. 0.65±0.11 mm Hg/%, P<0.001) after NTG. Cross-sectional vascular area calculated using this automated oscillometric measurement correlated with ultrasound measurement and showed good reproducibility. Therefore, this is a reliable approach and this modality may have practical application to automatically assess muscular artery diameter and elasticity in clinical or epidemiological settings.