Relationship between EMG-detected and ultrasound-detected fasciculations in amyotrophic lateral sclerosis: A prospective cohort study

ObjectivesFasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).MethodsThirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.ResultsThe mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).ConclusionSmall FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.SignificanceClinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.     

Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan

ObjectiveTo determine which compound muscle action potential (CMAP) scan-derived electrophysiological markers are most sensitive for monitoring disease progression in amyotrophic lateral sclerosis (ALS), and whether they hold value for clinical trials.MethodsWe used four independent patient cohorts to assess longitudinal patterns of a comprehensive set of electrophysiological markers including their association with the ALS functional rating scale (ALSFRS-R). Results were translated to trial sample size requirements.ResultsIn 65 patients, 225 thenar CMAP scan recordings were obtained. Electrophysiological markers showed extensive variation in their longitudinal trajectories. Expressed as standard deviations per month, motor unit number estimation (MUNE) values declined by 0.09 (CI 0.07–0.12), D50, a measure that quantifies CMAP scan discontinuities, declined by 0.09 (CI 0.06–0.13) and maximum CMAP by 0.05 (CI 0.03–0.08). ALSFRS-R declined fastest (0.12, CI 0.08 – 0.15), however the between-patient variability was larger compared to electrophysiological markers, resulting in larger sample sizes. MUNE reduced the sample size by 19.1% (n = 388 vs n = 314) for a 6-month study compared to the ALSFRS-R.ConclusionsCMAP scan-derived markers show promise in monitoring disease progression in ALS patients, where MUNE may be its most suitable derivate.SignificanceMUNE may increase clinical trial efficiency compared to clinical endpoints.     

The evolving role of surface electromyography in amyotrophic lateral sclerosis: A systematic review

ObjectiveAmyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS.MethodsWe searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients.ResultsA wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials.ConclusionSurface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians.SignificanceSurface EMG techniques can enrich effective biomarker development in ALS.     

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.     

Early focality and spread of cortical dysfunction in amyotrophic lateral sclerosis: A regional study across the motor cortices

ObjectiveTo characterise the regional cortical patterns underlying clinical symptomatology in amyotrophic lateral sclerosis (ALS).Methods138 patients prospectively underwent transcranial magnetic stimulation studies from hand and leg cortical regions of each hemisphere, obtaining motor evoked potentials from all four limbs. Patients were categorised by clinical phenotype and underwent clinical and peripheral evaluation of disease.ResultsCortical dysfunction was evident across the motor cortices, with reduction in short-interval intracortical inhibition (SICI) suggesting the presence of widespread cortical hyperexcitability, most prominently from clinically affected regions (hand p < 0.0001; leg p < 0.01). In early disease, cortical abnormalities were asymmetric between hemispheres, focally corresponding to clinical site-of-onset (p < 0.05). Degrees of cortical dysfunction varied between phenotypes, with the bulbar-onset cohort demonstrating greatest reduction in SICI (p = 0.03).ConclusionsThe pattern of cortical dysfunction appears linked to clinical evolution in ALS, with early focal asymmetry preceding widespread changes in later disease. Cortical differences across phenotypes may influence clinical variability.SignificanceThis is the first study to extensively map cortical abnormalities from multiple motor regions across hemispheres. The early cortical signature mirrors symptom laterality, supporting a discrete region of disease onset. Phenotypes appear to exist within a pathophysiological continuum, but cortical heterogeneity may mediate observed differences in clinical outcome.     

Practice-dependent motor cortex plasticity is reduced in non-disabled multiple sclerosis patients

ObjectivesSkill acquisition after motor training involves synaptic long-term potentiation (LTP) in primary motor cortex (M1). In multiple sclerosis (MS), LTP failure ensuing from neuroinflammation could contribute to worsen clinical recovery. We therefore addressed whether practice-dependent plasticity is altered in MS.MethodsEighteen relapsing-remitting (RR)-MS patients and eighteen healthy controls performed 600 fast abductions of index finger in 30 blocks of 20 movements. Before and after practice, transcranial magnetic stimulation (TMS) was delivered over the hot spot of the trained first dorsal interosseous muscle. Movements kinematics, measures of cortical excitability, and the input/output curves of motor evoked potentials (MEPs) were assessed.ResultsKinematic variables of movement improved with practice in patients and controls to a similar extent, although patients showed lower MEPs amplitude increase after practice. Practice did not change the difference in resting motor threshold values observed between patients and controls, nor did modulate short-interval intracortical inhibition. Clinical/radiological characteristics were not associated to practice-dependent effects.ConclusionsPractice-induced reorganization of M1 is altered in non-disabled RR-MS patients, as shown by impaired MEPs modulation after motor learning.SignificanceThese findings suggest that in RR-MS physiological mechanisms of practice-dependent plasticity are altered.     

Effect of repetitive transcranial magnetic stimulation combined with robot-assisted training on wrist muscle activation post-stroke

ObjectiveTo compare the effects of active assisted wrist extension training, using a robotic exoskeleton (RW), with simultaneous 5 Hz (rTMS + RW) or Sham rTMS (Sham rTMS + RW) over the ipsilesional extensor carpi radialis motor cortical representation, on voluntary wrist muscle activation following stroke.MethodsThe two training conditions were completed at least one week apart in 13 participants >1-year post-stroke. Voluntary wrist extensor muscle activation (motor unit (MU) recruitment thresholds and firing rate modulation in a ramp-hold handgrip task), ipsilesional corticospinal excitability (motor evoked potential [MEP] amplitude) and transcallosal inhibition were measured Pre- and Post-training.ResultsFor MUs active both Pre and Post training, greater reductions in recruitment thresholds were found Post rTMS + RW training (p = 0.0001) compared to Sham rTMS + RW (p = 0.16). MU firing rate modulation increased following both training conditions (p = 0.001). Ipsilesional MEPs were elicited Pre and Post in only 5/13 participants. No significant changes were seen in ipsilesional corticospinal excitability and transcallosal inhibition measures (p > 0.05).ConclusionsFollowing a single rTMS + RW session in people >1-year post-stroke, changes were found in voluntary muscle activation of wrist extensor muscles. Alterations in ipsilesional corticospinal or interhemispheric excitability were not detected.SignificanceThe effects of rTMS + RW on muscle activation warrant further investigation as post-stroke rehabilitation strategy.     

Bradykinesia in Alzheimer’s disease and its neurophysiological substrates

ObjectiveAlzheimer’s disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer’s disease.MethodsTwenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation.ResultsPatients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer’s disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery.ConclusionThis study provides new information on the pathophysiology of altered voluntary movements in Alzheimer’s disease.SignificanceThe study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer’s disease.     

SPiQE: An automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis

ObjectivesFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool.MethodsSix ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model’s predictive ability.ResultsBy applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/? 0.2 SEM), specificity of 91.6% (+/? 0.1 SEM) and classification accuracy of 87.9% (+/? 0.1 SEM). An amplitude exclusion threshold (100 μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p = 0.394).ConclusionWe have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE).SignificanceLongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.     

Vestibular evoked myogenic potentials and their clinical utility in patients with amyotrophic lateral sclerosis

ObjectiveTo evaluate the diagnostic value of vestibular evoked myogenic potentials (VEMPs) in the assessment of brainstem function integrity in patients with amyotrophic lateral sclerosis (ALS).MethodsThis was a prospective case-control study including 30 definite or probable ALS patients divided into two groups (with or without brainstem involvement) and 30 healthy controls. Cervical (c-), masseter (m-) and ocular VEMP (o-VEMP) measurements were obtained for all the participants.ResultsThe c-VEMP mean p13 and n23 were significantly prolonged in the ALS patients. The interside peak differences in p13 and n23 of c-VEMP and in n10 and p15 of o-VEMP were significantly prolonged. The rates of alteration in c-VEMP, m-VEMP and o-VEMP in the ALS patients were 67%, 40%, and 45%, respectively. The ALS patients with brainstem involvement had a significantly higher percentage of VEMP abnormalities than did those without brainstem involvement (p = 0.027).Conclusionsc-VEMP is a sensitive tool to detect lower levels of brainstem involvement. Impairments in o-VEMP and m-VEMP indicate involvement of the upper brainstem. The use of combined VEMPs may provide useful insights into the pathophysiological mechanism of ALS.SignificanceVEMPs may be useful in the evaluation of brainstem dysfunction in ALS patients.     

Motor Unit Number Index (MUNIX) of hand muscles is a disease biomarker for adult spinal muscular atrophy

ObjectiveThere is still insufficient knowledge about natural history in adult spinal muscular atrophy, thus valid markers for treatment and disease monitoring are urgently needed.MethodsWe studied hand muscle innervation pattern of 38 adult genetically confirmed 5q spinal muscular atrophy (SMA) patients by the motor unit number index (MUNIX) method. Data were compared to healthy controls and amyotrophic lateral sclerosis (ALS) patients and systematically correlated to typical disease-relevant scores and other clinical as well as demographic characteristics.ResultsDenervation of hand muscles in adult SMA was not evenly distributed. By calculation of the MUNIX ratios, we identified a specific hand muscle wasting pattern for SMA which is different to the split hand in ALS. Furthermore, MUNIX parameters strongly correlated with established disease course parameters independent of disease stages.ConclusionWe found a pathophysiological remarkable denervation pattern of hand muscles, a ‘reversed split hand’. MUNIX of single hand muscles correlated well with disease severity and thus represents an easily available biomarker for adult SMA.SignificanceOur data show the power of the MUNIX method as a biomarker for upcoming questions in adult SMA.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

A new potential specifically marks the sensory thalamus in anaesthetised patients

ObjectiveDuring deep brain stimulation (DBS) surgery, we analysed somatosensory evoked potentials (SSEPs) using microelectrode recordings (MERs) in patients under general anaesthesia.MethodsWe obtained MERs from 5 patients with refractory epilepsy. Off-line analysis isolated local field potentials (LFPs, 2–200 Hz) and high frequency components (HFCs, 0.5–5 kHz). Trajectories were reconstructed off-line.ResultsThe ventral caudate (V.c.) nucleus was most frequently recorded from (171 mm). Very high frequency oscillations (VHFOs) were recorded up to 8 mm in length from all 4 electrodes but were most frequently recorded from the V.c. The properties of VHFOs were similar among all nuclei (frequency >1500 Hz, amplitude ∼3 µV, starting time ∼14 ms, duration 8–9 ms). Consecutive recordings did not show any synchronization or propagation, but a new kind of potential (high frequency oscillation, HFO) appeared abruptly inside the V.c. (frequency = 848 ± 66 Hz, amplitude = 5.2 ± 1.8 µV starting at 17.7 ± 0.5 ms, spanning 3.4 ± 0.3 ms).ConclusionsVHFOs are widely extending and cannot be ascribed to the V.c. HFOs in patients under general anaesthesia can serve as a landmark to identify the V.c. in thalamic DBS surgery.SignificanceThalamic processing involves nuclei other than the V.c, and HFO can be used to improve DBS surgery.     

Gold Coast diagnostic criteria increase sensitivity in amyotrophic lateral sclerosis

ObjectiveThis study evaluates diagnostic accuracy of the proposed ‘Gold Coast’ (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS).MethodsFive European centres retrospectively sampled consecutive patients referred for electromyography on suspicion of ALS. Patients were classified according to the GC criteria, the revised El Escorial (rEE) criteria and the Awaji (AW) criteria without and with the ‘Possible’ category (+ Poss). Reference standard was ALS confirmed by disease progression at follow-up.ResultsOf 404 eligible patients 272 were diagnosed as ALS, 94 had mimicking disorders, 35 were lost for follow-up, and three had insufficient data. Sensitivity for the GC criteria was 88.2% (95% CI: 83.8-91.8%), which was higher than for previous criteria, of which the AW + Poss criteria reached the highest sensitivity of 77.6% (95% CI: 72.2–82.4%) (p < 0.001). Specificity was high for all criteria. The increase in sensitivity for the GC criteria was mainly due to the inclusion of 28 patients with progressive muscular atrophy (PMA).ConclusionsThe simpler GC criteria increase the sensitivity, primarily due to considering PMA as a form of ALS with high specificity preserved.SignificanceThis validation study supports that GC criteria should be used in clinical practice and may be used for inclusion in trials.     

Recording activity in proximal muscle networks with surface EMG in assessing infant motor development

ObjectiveTo develop methods for recording and analysing infant’s proximal muscle activations.MethodsSurface electromyography (sEMG) of truncal muscles was recorded in three months old infants (N = 18) during spontaneous movement and controlled postural changes. The infants were also divided into two groups according to motor performance. We developed an efficient method for removing dynamic cardiac artefacts to allow i) accurate estimation of individual muscle activations, as well as ii) quantitative characterization of muscle networks.ResultsThe automated removal of cardiac artefacts allowed quantitation of truncal muscle activity, which showed predictable effects during postural changes, and there were differences between high and low performing infants. The muscle networks showed consistent change in network density during spontaneous movements between supine and prone position. Moreover, activity correlations in individual pairs of back muscles linked to infant́s motor performance.ConclusionsThe hereby developed sEMG analysis methodology is feasible and may disclose differences between high and low performing infants. Analysis of the muscle networks may provide novel insight to central control of motility.SignificanceQuantitative analysis of infant’s muscle activity and muscle networks holds promise for an objective neurodevelopmental assessment of motor system.     

Muscle responses to radicular stimulation during lumbo-sacral dorsal rhizotomy for spastic diplegia: Insights to myotome innervation

ObjectiveMost of knowledge on muscle radicular innervation was from explorations in root/spinal cord pathologies. Direct and individual access to each of the lumbar-sacral -ventral and dorsal- nerve roots during dorsal rhizotomy for spastic diplegia allows precise study of the corresponding muscle innervation. Authors report the lumbo-sacral segmental myotomal organization obtained from recordings of muscle responses to root stimulation in a 20-children prospective series.MethodsSeven key-muscles in each lower limb and anal sphincter were Electromyography (EMG)-recorded and clinically observed by physiotherapist during L2-to-S2 dorsal rhizotomy. Ventral roots (VR), for topographical mapping, and dorsal roots (DR), for segmental excitability testing, were stimulated, just above threshold for eliciting muscular response.ResultsIn 70% of the muscles studied, VR innervation was pluri-radicular, from 2-to-4 roots, with 1 or 2 roots being dominant at each level. Overlapping was important. Muscle responses to DR stimulation were 1.75 times more extended compared to VR stimulation. Inter-individual variability was important.ConclusionsAccuracy of root identification and stimulation with the used method brings some more precise information to radicular functional anatomy.SignificanceThose neurophysiological findings plead for performing Intra-Operative Neuromonitoring when dealing with surgery in the lumbar-sacral roots.     

Near-fiber electromyography

ObjectiveDescribe and evaluate the concepts of near fiber electromyography (NFEMG), the features used, including near fiber motor unit potential (NFMUP) duration and dispersion, which relate to motor unit distal axonal branch and muscle fiber conduction time dispersion, and NFMUP segment jitter, a new measure of the temporal variability of neuromuscular junction transmission (NMJ), and axonal branch and muscle fibre conduction for the near fibres (i.e. NF jitter), and the methods for obtaining their values.MethodsTrains of high-pass filtered motor unit potentials (MUPs) (i.e. NFMUP trains) were extracted from needle-detected EMG signals to assess changes in motor unit (MU) morphology and electrophysiology caused by neuromuscular disorders or ageing. Evaluations using simulated needle-detected EMG data were completed and example human data are presented.ResultsNFEMG feature values can be used to detect axonal sprouting, conduction slowing and NMJ transmission delay as well as changes in MU fiber diameter variability, and NF jitter. These changes can be detected prior to alterations of MU size or numbers.ConclusionsThe evaluations clearly demonstrate and the example data support that NFMUP duration and dispersion reflect MU distal axonal branching, conduction slowing and NMJ transmission delay and/or MU fiber diameter variability and that NFMUP jiggle and segment jitter reflect NF jitter.SignificanceNFEMG can detect early changes in MU morphology and/or electrophysiology and has the potential to augment clinical diagnosis and tracking of neuromuscular disorders.     

Relationship between GABA levels and task-dependent cortical excitability in children with attention-deficit/hyperactivity disorder

ObjectiveCompared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).MethodsAcross two sites, 37 children with ADHD and 45 TD children, ages 8–12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models.ResultsIn both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.ConclusionsIn children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.SignificanceEvaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.     

Motor unit reserve capacity in spinal muscular atrophy during fatiguing endurance performance

ObjectiveTo investigate the availability of any motor unit reserve capacity during fatiguing endurance testing in patients with spinal muscular atrophy (SMA).MethodsWe recorded surface electromyography (sEMG) of various muscles of upper- and lower extremities of 70 patients with SMA types 2–4 and 19 healthy controls performing endurance shuttle tests (ESTs) of arm and legs. We quantitatively evaluated the development of fatigability and motor unit recruitment using time courses of median frequencies and amplitudes of sEMG signals. Linear mixed effect statistical models were used to evaluate group differences in median frequency and normalized amplitude at onset and its time course.ResultsNormalized sEMG amplitudes at onset of upper body ESTs were significantly higher in patients compared to controls, yet submaximal when related to maximal voluntary contractions, and showed an inverse correlation to SMA phenotype. sEMG median frequencies decreased and amplitudes increased in various muscles during execution of ESTs in patients and controls.ConclusionsDecreasing median frequencies and increasing amplitudes reveal motor unit reserve capacity in individual SMA patients during ESTs at submaximal performance intensities.SignificancePreserving, if not expanding motor unit reserve capacity may present a potential therapeutic target in clinical care to reduce fatigability in individual patients with SMA.     

Early nociceptive evoked potentials (NEPs) recorded from the scalp

ObjectiveNeurophysiological investigation of nociceptive pathway has so far been limited to late cortical responses. We sought to detect early components of the cortical evoked potentials possibly reflecting primary sensory activity.MethodsThe 150 IDE micropatterned electrode was used to selectively activate Aδ intraepidermic fibres of the right hand dorsum in 25 healthy subjects and 3 patients suffering from trigeminal neuralgia. Neurographic recordings were performed to assess type of stimulated fibres and check selectivity. Cortical evoked potentials were recorded from C3′-Fz and Cz-Au1.ResultsNeurographic recordings confirmed selective activation of Aδ fibres. Early components were detected after repetitive stimulation (0.83/s rate and 250–500 averages); the first negative component occured at 40 ms (N40) on the contralateral scalp.ConclusionsThe provided data support the hypothesis that N40 could be the cortical primary response conducted by fast Aδ fibres.SignificanceThis is the first report of early, possibly primary, cortical responses in humans by nociceptive peripheral stimulation. Although not perfected yet to allow widespread diagnostic use, this is probably the only method to allow fully objective evaluation of the nociceptive system, with important future implications in experimental and clinical neurophysiology.