Kazumoto Shibuya

Ultrasonographic detection of fasciculations markedly increases diagnostic sensitivity of ALS.

Objectives: To study the utility of muscle ultrasound (US) for detection of fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis (ALS). Fasciculations are characteristic features of ALS, and US can detect them easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves. Methods: In 81 consecutive patients with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus lateralis, and tibialis anterior), and diagnostic category were determined by revised El Escorial criteria and Awaji criteria. Results: Fasciculations were much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion of the patients with definite or probable ALS was 48% by revised El Escorial criteria and 79% by Awaji criteria using US. Conclusions: Muscle US is a practical and efficient tool to detect fasciculations, particularly in the tongue. A combination of US and EMG substantially increases the diagnostic sensitivity of ALS.

Amyotrophic lateral sclerosis and motor neuron syndromes in Asia

While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.

Threshold tracking transcranial magnetic stimulation: Effects of age and gender on motor cortical function

OBJECTIVEnRecently, the utility of threshold tracking paired-pulse transcranial magnetic stimulation (TTTMS), to measure changes in cortical excitabilitability, has been established for diagnostic purposes across a range of neurological diseases. However, the impact of healthy aging on the GABA-ergic intracortical inhibitory system remains unclear. To improve the clinical applicability, TTTMS was performed across an age spectrum.nnnMETHODSnTTTMS, single-pulse TMS and nerve conduction studies (NCS) were performed in 113 healthy subjects aged between 20 and 83years (57 male and 56 female).nnnRESULTSnProlonged motor evoked potential (MEP) latency, increased central motor conduction time, decreased compound muscle action potential (CMAP) amplitude, prolonged F-wave latency and decreased neurophysiological index (NI), calculated from CMAP amplitude, latency and F-wave frequency, were observed as subjects aged. In contrast, short interval intracortical inhibition (SICI) and facilitation did not change. Compared to females, males exhibited a reduced SICI and NI along with longer MEP, CMAP with prolonged F-wave latencies. Multivariate analyses revealed similar results.nnnCONCLUSIONnUtilizing clinically applicable TTTMS protocols, findings suggest that GABA mediated intracortical inhibition may be greater in females but does not significantly change with age.nnnSIGNIFICANCEnThese findings may better inform the interpretation of diagnostic TTTMS studies in the clinical setting.

Neuromuscular transmission is not impaired in axonal Guillain–Barré syndrome

Background Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain–Barré syndrome (GBS). Methods Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies. Results All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking. Conclusion In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.

Detection of fasciculations in amyotrophic lateral sclerosis: The optimal ultrasound scan time.

This study seeks to elucidate the optimal scan time to detect fasciculations by using ultrasound in the diagnosis of amyotrophic lateral sclerosis (ALS).

Quantitative muscle ultrasound as a biomarker in Charcot-Marie-Tooth neuropathy

OBJECTIVEnThe utility of quantitative muscle ultrasound as a marker of disease severity in Charcot-Marie-Tooth (CMT) disease subtypes was investigated.nnnMETHODSnMuscle ultrasound was prospectively performed on 252 individual muscles from 21 CMT patients (9 CMT1A, 8 CMTX1, 4 CMT2A) and compared to 120 muscles from 10 age and gender-matched controls. Muscle ultrasound recorded echogenicity and thickness in representative muscles including first dorsal interosseus (FDI) and tibialis anterior (TA).nnnRESULTSnMuscle volume of FDI and thickness of TA correlated with MRC strength. Muscle echogenicity was significantly increased in FDI (65.05 vs 47.09; p<0.0001) and TA (89.45 vs 66.30; p<0.0001) of CMT patients. In TA, there was significantly higher muscle thickness (23 vs 18 vs 16mm; p<0.0001) and lower muscle echogenicity (80 vs 95 vs 108; p<0.0001) in CMT1A compared to CMTX1 and CMT2A. This corresponded to disease severity based on muscle strength (MRC grading CMT1A vs CMTX1 vs CMT2A: 59 vs 48 vs 44; p=0.002).nnnCONCLUSIONnIn CMT, quantitative muscle ultrasound of FDI and TA is a useful marker of disease severity.nnnSIGNIFICANCEnThe current findings suggest that quantitative muscle ultrasound has potential as a surrogate marker of disease progression in future interventional trials in CMT.

The evolution of motor cortical dysfunction in amyotrophic lateral sclerosis

OBJECTIVEnThe present study aimed to investigate alterations in cortical function in amyotrophic lateral sclerosis (ALS) related to disease progression.nnnMETHODSnIn total, clinical assessments were evaluated in 189 ALS patients, combined with assessment of cortical function utilising threshold tracking transcranial magnetic stimulation. Results were compared with disease stage. Disease stage was defined in three ways: (1) as a proportion of disease duration in deceased patients; (2) from the time of ALS onset; and (3) using the ALS rating scale-revised (ALSFRS-R).nnnRESULTSnProspective studies in ALS patients demonstrated decreased neurophysiological index (p<0.0001) and decreased compound muscle action potential (CMAP) (p<0.0001), combined with abnormalities of central function including prolonged central motor conduction time (CMCT) (p<0.05), increased motor evoked potential/CMAP amplitude ratio (p<0.0001) and decreased short interval intracortical inhibition (SICI) (p<0.001). SICI at 3ms (p<0.05, β=-0.21) and averaged SICI (p<0.05, β=-0.21) decreased with disease progression, measured using proportion of disease duration. Alternatively, using time from disease onset, CMCT prolonged with disease progression (p<0.01, β=0.25), while ALSFRS-R decline correlated with decreased SICI at 3ms (p<0.01, β=0.20).nnnCONCLUSIONSnClinical measures combined with assessment of cortical function established that SICI decreased with disease progression.nnnSIGNIFICANCEnThese findings may suggest dysfunction of inhibitory interneurons with disease progression.

Dynamic muscle ultrasound identifies upper motor neuron involvement in amyotrophic lateral sclerosis

Abstract Objective: The aim of the present study was to elucidate the pattern of change in bulbar muscles using ultrasound in patients diagnosed with amyotrophic lateral sclerosis (ALS). Methods: Changes in the mylohyoid and geniohyoid muscle complex (mylohyoid-geniohyoid-muscle-complex) thickness were recorded while swallowing 5u2009ml of water using M-mode ultrasound in 30 ALS patients compared to 20 healthy controls. The ratio of mylohyoid-geniohyoid-muscle-complex thickness as determined by the maximum thickness of mylohyoid-geniohyoid-muscle-complex during swallowing divided by thickness at rest, was compared between ALS patients and controls, with the correlation between thickness ratio, echogenicity and clinical parameters assessed. Results: Overall, the thickness ratio in ALS patients was 1.39u2009±u20090.23 (meanu2009±u2009SD) compared to 1.55u2009±u20090.17 in controls (pu2009<u20090.05). In sub-analysis, the thickness ratio was significantly decreased in ALS patients with bulbar-onset disease compared to those with limb-onset disease (pu2009<u20090.01) and controls (pu2009<u20090.01). Thickness ratio negatively correlated with the severity of upper motor neuron involvement in the bulbar region (pu2009<u20090.05). Conclusions: Bulbar muscle ultrasound represents a novel method to detect impaired mobility and thereby provides an objective assessment of upper motor neuron involvement in the bulbar region of ALS patients.

Novel therapies in development that inhibit motor neuron hyperexcitability in amyotrophic lateral sclerosis

ABSTRACT Introduction: Motor neuron hyperexcitability appears linked to the process of neurodegeneration in amyotrophic lateral sclerosis (ALS). As such, therapies that inhibit neuronal hyperexcitability may prove effective in arresting the progression of ALS. Area covered: We searched MEDLINE and ClinicalTrials.gov and selected randomised controlled trials that covered neuroprotective therapy. Riluzole has been established to reduce neuronal hyperexcitability. More recently, initial studies of Na+ channel blockers (mexiletine and flecainide) have been trialled. Separately, a trial of a K+ channel activator (retigabine) is underway, while edaravone is currently being considered for licensing by drug approval agencies based on a hypothesis that the elimination of free radicals may lead to protection of motor neurones. Expert commentary: Initial clinical trials with Na+ channel blockers have not yet established efficacy in ALS. Currently, retigabine is under evaluation as a potential therapy. Edaravone has recently been approved as a new therapeutic option for ALS in Japan.

Laterality of motor cortical function measured by transcranial magnetic stimulation threshold tracking.

Introduction: Threshold tracking paired‐pulse transcranial magnetic stimulation (TTTMS) examines cortical function and is useful for diagnosis of motor neuron disorders. Differences in cortical function have been identified between dominant and non‐dominant limbs using constant stimulus methods, but they remain unclear, potentially due to methodological differences. In this study we aimed to clarify differences in cortical function between dominant and non‐dominant limbs using TTTMS. Methods: Single‐pulse TMS, TTTMS, and nerve conduction studies were performed in 25 healthy, right‐handed participants by recording from the abductor pollicis brevis muscle. Results: There were no side‐to‐side differences observed in resting motor threshold, motor evoked potential (MEP) amplitude, MEP latency, central motor conduction time, cortical silent period, short‐interval intracortical inhibition and facilitation, compound muscle action potential (CMAP) amplitude, CMAP latency, F‐wave latency, or neurophysiological index. Conclusions: These findings suggest that, when using TTTMS, there are no differences in cortical function between dominant and non‐dominant hemispheres. Muscle Nerve 55: 424–427, 2017