A test to determine the site of abnormal neuromuscular refractoriness

Objective: The relative refractory period (RRP) of motor axons is an important parameter in nerve excitability tests of the recovery cycle (RC). Abnormalities may have a site in the axonal membrane, the neuromuscular junction, or in a dysfunction of the muscle. We aimed in this study to determine the site of abnormality, using a modified protocol of the conventional RC test, whereby an additional supramaximal stimulus is added at the same interstimulus interval as in RC recordings (RCSM). Methods: Twenty-four healthy subjects aged 37.8 ± 2.4 years (mean ± SE) were examined with median nerve excitability testing using RC and RCSM protocols at normal temperature (34.1 ± 0.2 °C). The recordings were repeated in 12 subjects after selective cooling of the thenar muscle (25.2 ± 0.7 °C) and in 12 subjects after cooling the nerve trunk at the wrist (24.9 ± 0.3 °C). Results: After cooling the nerve, RRP measured with RC and RCSM were prolonged similarly (medians by 1.8 ms, and 2.1 ms respectively). In contrast, cooling the muscle prolonged RRP measured with RC (by 1.3 ms), but did not significantly prolong RRP measured with RCSM. RRPs measured by RC and RCSM were significantly different when cooling was at the muscle (P = 5.10-4), but not when cooling was at the nerve (P = 0.57). Conclusions: A difference between RC and RCSM indicates abnormal excitability distal to the axonal membrane under the stimulating electrode. Significance: Combining RCSM with the conventional RC protocol should help to localize the site of abnormal neuromuscular refractoriness

CMAP Scan MUNE (MScan) - A Novel Motor Unit Number Estimation (MUNE) Method

Like other methods for motor unit number estimation (MUNE), compound muscle action potential (CMAP) scan MUNE (MScan) is a non-invasive electrophysiologic method to estimate the number of functioning motor units in a muscle. MUNE is an important tool for the assessment of neuropathies and neuronopathies. Unlike most MUNE methods in use, MScan assesses all the motor units in a muscle, by fitting a model to a detailed stimulus-response curve, or CMAP scan. It thereby avoids the bias inherent in all MUNE methods based on extrapolating from a small sample of units. Like 'Bayesian MUNE,' MScan analysis works by fitting a model, made up of motor units with different amplitudes, thresholds, and threshold variabilities, but the fitting method is quite different, and completed within five minutes, rather than several hours. The MScan off-line analysis works in two stages: first, a preliminary model is generated based on the slope and variance of the points in the scan, and second, this model is then refined by adjusting all the parameters to improve the fit between the original scan and scans generated by the model. This new method has been tested for reproducibility and recording time on 22 amyotrophic lateral sclerosis (ALS) patients and 20 healthy controls, with each test repeated twice by two blinded physicians. MScan showed excellent intra- and inter-rater reproducibility with ICC values of >0.98 and a coefficient of variation averaging 12.3 ± 1.6%. There was no difference in the intra-rater reproducibility between the two observers. Average recording time was 6.27 ± 0.27 min. This protocol describes how to record a CMAP scan and how to use the MScan software to derive an estimate of the number and sizes of the functioning motor units. MScan is a fast, convenient, and reproducible method, which may be helpful in diagnoses and monitoring disease progression in neuromuscular disorders

Neurology resident EEG training in Europe

OBJECTIVE: To detail current European EEG education practices and compare European and U.S. EEG teaching systems. METHODS: A 19-question online survey focused on EEG clinical practices and residency training was emailed to all 47 European Academy of Neurology Societies. RESULTS: Thirty-two (68 %) out of the 47 Societies completed the survey. In half of countries, general neurologists are either among the providers or the only providers who typically read EEGs. The number of weeks devoted to EEG learning required to graduate ranged from none to 26, and it was expected to be continuous in one country. In most countries (n = 17/32), trainees read \u3e40 EEGs per EEG rotation, and the most commonly interpreted studies are routine and prolonged routine EEGs. Rotations involve clinic/outpatient (90 %), epilepsy monitoring unit/inpatient (60 %), or both (50 %). Roughly half of countries do not use objective measures to assess EEG competency. The most reported educational methods are teaching during EEG rotation and yearly didactics, and the most reported education barriers are insufficient didactics and insufficient EEG exposure. CONCLUSIONS: We suggest neurology educators in Europe, especially in those countries where EEGs are read by general neurologists, consider ensuring that residency EEG learning is mandatory and establishing objective measures in teaching and evaluating competency. SIGNIFICANCE: Similar to the U.S., neurology resident EEG training in Europe is highly variable

Short interval intracortical inhibition: Variability of amplitude and threshold-tracking measurements with 6 or 10 stimuli per point

Reduced short-interval intracortical inhibition (SICI) in motor neuron disease has been demonstrated by amplitude changes (A-SICI) and threshold-tracking (T-SICI) using 10 stimuli per inter-stimulus interval (ISI). To test whether fewer stimuli would suffice, A-SICI and T-SICI were recorded twice from 30 healthy subjects using 6 and 10 stimuli per ISI. Using fewer stimuli increased mean A-SICI variances by 23.8% but the 7.3% increase in T-SICI variance was not significant. We conclude that our new parallel threshold-tracking SICI protocol, with 6 stimuli per ISI, can reduce time and stimulus numbers by 40% without appreciable loss of accuracy

Conventional and threshold-tracking transcranial magnetic stimulation tests for single-handed operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short-and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short-and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single-and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single-and paired-pulse TMS protocols. This paper shows how to record a number of single-and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS

Imaging Neurodegenerative Metabolism in Amyotrophic Lateral Sclerosis with Hyperpolarized [1-13C]pyruvate MRI

The cause of amyotrophic lateral sclerosis (ALS) is still unknown, and consequently, early diagnosis of the disease can be difficult and effective treatment is lacking. The pathology of ALS seems to involve specific disturbances in carbohydrate metabolism, which may be diagnostic and therapeutic targets. Magnetic resonance imaging (MRI) with hyperpolarized [1-(13)C]pyruvate is emerging as a technology for the evaluation of pathway-specific changes in the brain’s metabolism. By imaging pyruvate and the lactate and bicarbonate it is metabolized into, the technology is sensitive to the metabolic changes of inflammation and mitochondrial dysfunction. In this study, we performed hyperpolarized MRI of a patient with newly diagnosed ALS. We found a lateralized difference in [1-(13)C]pyruvate-to-[1-(13)C]lactate exchange with no changes in exchange from [1-(13)C]pyruvate to (13)C-bicarbonate. The 40% increase in [1-(13)C]pyruvate-to-[1-(13)C]lactate exchange corresponded with the patient’s symptoms and presentation with upper-motor neuron affection and cortical hyperexcitability. The data presented here demonstrate the feasibility of performing hyperpolarized MRI in ALS. They indicate potential in pathway-specific imaging of dysfunctional carbohydrate metabolism in ALS, an enigmatic neurodegenerative disease

The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability

Though a common symptom, fatigue is difficult to define and investigate, occurs in a wide variety of neurological and systemic disorders, with differing pathological causes. It is also often accompanied by a psychological component. As a symptom of long-term COVID-19 it has gained more attention. In this review, we begin by differentiating fatigue, a perception, from fatigability, quantifiable through biomarkers. Central and peripheral nervous system and muscle disorders associated with these are summarised. We provide a comprehensive and objective framework to help identify potential causes of fatigue and fatigability in a given disease condition. It also considers the effectiveness of neurophysiological tests as objective biomarkers for its assessment. Among these, twitch interpolation, motor cortex stimulation, electroencephalography and magnetencephalography, and readiness potentials will be described for the assessment of central fatigability, and surface and needle electromyography (EMG), single fibre EMG and nerve conduction studies for the assessment of peripheral fatigability. The purpose of this review is to guide clinicians in how to approach fatigue, and fatigability, and to suggest that neurophysiological tests may allow an understanding of their origin and interactions. In this way, their differing types and origins, and hence their possible differing treatments, may also be defined more clearly

Muscle velocity recovery cycles in myopathy.

OBJECTIVE To understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies. METHODS 42 patients with quantitative electromyography (qEMG) and biopsy or genetic verified myopathy and 42 healthy controls were examined with qEMG, MVRC and RAMP, all recorded from the anterior tibial muscle. RESULTS There were significant differences in the motor unit potential (MUP) duration, the early and late supernormalities of the MVRC and the RAMP latencies in myopathy patients compared to controls (p < 0.05 apart from muscle relatively refractory period (MRRP)). When dividing into subgroups, the above-mentioned changes in MVRC and RAMP parameters were increased for the patients with non-inflammatory myopathy, while there were no significant changes in the group of patients with inflammatory myopathy. CONCLUSIONS The MVRC and RAMP parameters can discriminate between healthy controls and myopathy patients, more significantly for non-inflammatory myopathy. MVRC differences with normal MRRP in myopathy differs from other conditions with membrane depolarisation. SIGNIFICANCE MVCR and RAMP may have a potential in understanding disease pathophysiology in myopathies. The pathogenesis in non-inflammatory myopathy does not seem to be caused by a depolarisation of the resting membrane potential but rather by the change in sodium channels of the muscle membrane