Exploring the effect of the nerve conduction distance on the MScanFit method ofmotor unit number estimation (MUNE).

OBJECTIVE: MScanFit motor unit number estimation (MUNE) is a sensitive method for detecting motor unit loss and has demonstrated high reproducibility in various settings. In this study, our aim was to assess the outputs of this method when the nerve conduction distance is increased. METHODS: MScanFit recordings were obtained from the abductor digiti minimi muscle of 20 healthy volunteers. To evaluate the effect of nerve conduction distance, the ulnar nerve was stimulated from the wrist and elbow respectively. Reproducibility of MUNE, compound muscle action potential (CMAP), and other motor unit parameters were assessed using intraclass correlation coefficients (ICCs). RESULTS: Motor unit numbers obtained from stimulation at the wrist and elbow did not significantly differ and exhibited strong consistency in the ICC test (120.3 ± 23.7 vs. 118.5 ± 27.9, p > 0.05, ICC: 0.88). Similar repeatability values were noted for other parameters. However, the Largest Unit (%) displayed notable variability between the two regions and exhibited a negative correlation with nerve conduction distance. CONCLUSION: Our findings indicate that MScanFit can consistently calculate motor unit numbers and most of its outputs without substantial influence from nerve conduction distance. Exploring MScanFit's capabilities in various settings could enhance our understanding of its strengths and limitations for extensive use in clinical practice.

Impact of Acute High-intensity Interval Training on Cortical Excitability, M1-related Cognitive Functions, and Myokines: A Randomized Crossover Study.

High-intensity interval training (HIIT) is a time-efficient, safe, and feasible exercise type that can be utilized across different ages and health status. This randomized cross-over study aimed to investigate the effect of acute HIIT on cortical excitability, M1-related cognitive functions, cognition-related myokines, brain-derived neurotrophic factor (BDNF), and Cathepsin B (CTSB). Twenty-three sedentary young adults (mean age: 22.78 years ± 2.87; 14 female) participated in a cross-over design involving two sessions: either 23 min of HIIT or seated rest. Before and after the sessions, cortical excitability was measured using transcranial magnetic stimulation, and M1-related cognitive functions were assessed by the n-back test and mental rotation test. Serum levels of BDNF and CTSB were assessed using the ELISA method before and after the HIIT intervention. We demonstrated that HIIT improved mental rotation and working memory, and increased serum levels of BDNF and CTSB, whereas cortical excitability did not change. Our findings provide evidence that one session of HIIT is effective on M1-related cognitive functions and cognition-related myokines. Future research is warranted to determine whether such findings are transferable to different populations, such as cognitively at-risk children, adults, and older adults, and to prescribe effective exercise programs.

Threshold tracking transcranial magnetic stimulation and neurofilament light chain as diagnostic aids in ALS.

OBJECTIVE: There is a need for sensitive biomarkers in amyotrophic lateral sclerosis (ALS), to enable earlier diagnosis and to help assess potential treatments. The main objective of this study was to compare two potential biomarkers, threshold-tracking short-interval cortical inhibition (T-SICI), which has shown promise as a diagnostic aid, and neurofilament light chains (NfL). METHODS: Ninety-seven patients with ALS (mean age 67.1 ± 11.5 years) and 53 ALS mimics (aged 62.4 ± 12.9) were included. Mean disease duration was 14 months ±14.1. Patients were evaluated with revised ALS functional rating score (ALSFRS-R), Penn upper motor neuron score (UMNS), muscle strength using the Medical Research Council (MRC) score and examined with T-SICI, quantitative electromyography (EMG), and NfL measured in spinal fluid. RESULTS: NfL increased with increasing UMNS (rho = 0.45, p = 8.2 × 10-6) whereas T-SICI at 2.5 ms paradoxically increased toward normal values (rho = 0.53, p = 1.9 × 10-7). However, these two measures were uncorrelated. Discrimination between ALS patients and mimics was best for NfL (area under ROC curve 0.842, sensitivity 84.9%, specificity 83.5%), compared with T-SICI (0.675, 39.6%, 91.8%). For the patients with no UMN signs, NfL also discriminated best (0.884, 89.3%, 82.6%), compared with T-SICI (0.811, 71.4%, 82.6%). However, when combining NfL and T-SICI, higher AUCs of 0.854 and 0.922 and specificities of 93.8 and 100 were found when considering all patients and patients with no UMN signs, respectively. INTERPRETATION: Both T-SICI and NfL correlated with UMN involvement and combined, they provided a strong discrimination between ALS patients and ALS mimics.

Long-interval afferent inhibition measurement using two different methods: Normative values, repeatability and reliability.

BACKGROUND: The mechanism of Short-Latency Afferent Inhibition (SAI) is relatively well understood. In contrast, Long-Latency Afferent Inhibition (LAI) has not been as extensively studied as SAI, and its underlying mechanism remains unclear. OBJECTIVE/HYPOTHESIS: This study had two primary objectives: first, to determine the optimal ISIs for LAI measured by amplitude changes (A-LAI) using high-resolution ISI ranges; and second, to compare measurements of LAI by threshold-tracking (T-LAI). METHODS: Twenty-eight healthy volunteers (12 males aged 24- 45 years) participated in the study. Paired peripheral electrical and transcranial magnetic stimulation (TMS) stimuli (TS1mv) were applied at varying (ISIs)- 100, 200, 250, 300, 350, 400, 450, 500, 550, 600, 700, 800, 900, 1000 ms. RESULTS: Both A-LAI and T-LAI showed that LAI decreased progressively from a peak at 200 or 250 ms to 1000 ms. Using the A-LAI method, pronounced inhibition was observed at three specific ISIs: 100 ms, 250 ms and 450 ms. When A-LAI values were converted to equivalent threshold changes, they did not differ significantly from T-LAI. Reliability at distinguishing individuals, as indicated by intraclass correlation coefficient (ICC) was greater for A-LAI, with a peak value of 0.82 at 250 ms. CONCLUSION(S): The study demonstrates that ISIs of 100 ms and 250 ms can be reliably used in amplitude measurement LAI. The study demonstrates that both LAI measurements record a similar decline of inhibition with increasing ISI.

Caffeine and cortical excitability, as measured with paired-pulse transcranial magnetic stimulation.

INTRODUCTION/AIMS: The transcranial magnetic stimulation tests of short-interval intracortical inhibition (SICI) by both conventional amplitude measurements (A-SICI) and threshold-tracking (T-SICI) are important methods to investigate intracortical inhibitory circuits, and T-SICI has been proposed to aid the diagnosis of amyotrophic lateral sclerosis. Beverages containing caffeine are widely consumed, and caffeine has been reported to affect cortical excitability. The aim of this study was to determine whether these SICI tests are affected by caffeine. METHODS: Twenty-four healthy subjects (13 females, 11 males, aged from 19 to 31, mean: 26.2 ± 2.4 years) were studied in a single fixed-dose randomized double-blind placebo-controlled cross-over trial of 200 mg caffeine or placebo ingested as chewing gum. A-SICI and T-SICI, using parallel tracking (T-SICIp), were performed before and after chewing gum. RESULTS: There was no significant change in SICI parameters after placebo in A-SICI (p > .10) or T-SICIp (p > .30), and no significant effect of caffeine was found on A-SICI (p > .10) or T-SICIp (p > .50) for any of the interstimulus intervals. DISCUSSION: There is no need for caffeine abstention before measurements of SICI by either the T-SICI or A-SICI measurements.

Excitability of somatosensory cortex is increased in ALS: A SEP recovery function study.

OBJECTIVE: Neuronal loss in the somatosensory, as well as the motor cortex in amyotrophic lateral sclerosis (ALS), indicative of a structural abnormality has been reported. Previously we have shown that afferent inhibition was impaired in ALS, suggestive of sensory involvement. In this study, we aimed to evaluate excitability changes in the somatosensory cortex of ALS patients. METHODS: ALS patients underwent a paired pulse somatosensory evoked potential (SEP) paradigm at various interstimulus intervals (ISI). The amplitude ratio obtained by dividing the amplitude of paired pulse SEP stimulation S2 (paired pulse stimulation) to S1 (the single pulse stimulation) was considered the somatosensory cortex excitability parameter. Findings were compared to the results obtained from healthy controls. Resting motor threshold (RMT) was also assessed in the ALS group. RESULTS: An increased S2/S1 ratio was found in the ALS group in every ISI examined. Additionally, the reduced inhibition correlated negatively with forced vital capacity, Medical Research Council sum score, median nerve compound muscle action potential amplitude, while there was a positive association with Penn upper motor neuron score and sural nerve conduction velocity. No correlation existed with RMT. CONCLUSIONS: Our findings demonstrated increased somatosensory cortical excitability in ALS, which was associated with clinical parameters such as reduced pulmonary function and motor strength. SIGNIFICANCE: Somatosensory cortical excitability is impaired in ALS. Whether this is associated with increased motor cortical excitability requires further studies.

Evaluation of Auditory Temporal Discrimination Thresholds in Migraine Patients.

INTRODUCTION: Although vestibular migraine is well defined, the effects of migraine on the auditory system have not been clearly identified yet. The aim of this study was to determine the effect of migraine on the auditory system. METHODS: Migraine patients without hearing loss were included in the study. Group 1 consisted of patients with migraine pain, group 2 consisted of patients with migraine in the interictal period, and group 3 consisted of healthy volunteers with similar demographic characteristics to groups 1 and 2. Random gap detection test was applied to all 3 groups. Additionally, group 2 and group 3 patients were evaluated with the auditory cortical potentials and the mismatch negativity test. RESULTS: There was a statistically significant difference between the 3 groups in the random gap detection test. There was no statistically significant difference in auditory cortical potentials between group 2 and group 3; however, a statistically significant difference was found between the groups in terms of mismatch negativity test latency. CONCLUSION: An auditory pathway may be affected in migraine patients, although hearing tests are normal. This interaction continues between attacks, being more evident during the pain period. Therefore, disorders of hearing or speech perception in migraine patients should be evaluated by further audiological tests.

Visual temporal discrimination is impaired in patients with migraine without aura.

BACKGROUND AND OBJECTIVE: Dysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test. METHODS: A total of 45 participants were enrolled in this prospective exploratory study. In all, 15 patients had migraine without aura and 15 healthy volunteers were analyzed in the study. The VTD threshold (VTDT) was measured using light-emitting diode lights to perceive two separate visual stimuli as clearly distinct. VTD was tested during the attack and the interictal period. The disease duration, attack side, visual analog scale for pain, accompanying symptoms, and allodynia were recorded during the attack. RESULTS: The VTDT of each visual field in both attack (mean [SD] 102.3 [38.4] ms for the right visual field and 106.3 [52.2] ms for the left) and the interictal periods (mean [SD] 75.2 [27.9] ms for the right and 78.2 [27.9] ms for the left) were significantly higher than in the control group (mean [SD] 45.3 [9.9] ms for the right and 48.2 [11.9] ms for the left) (p < 0.001, p < 0.001, p = 0.003, p < 0.001, respectively). The ipsilateral threshold during the attack was significantly prolonged compared to the interictal period (mean [SD] 143.8 [53.8] vs. 78 [19.6] ms, p = 0.025) and the contralateral threshold during the attack (mean [SD] 143.8 [53.8] vs. 71.9 [14.1] ms, p = 0.025). The ipsilateral threshold was significantly correlated with the visual analog score (r = 0.894, p < 0.001) and frequency of the attacks (r = 0.696, p = 0.004), but not correlated with photophobia. CONCLUSION: The VTDTs are prolonged both ictally and interictally in patients with migraine without aura attacks. Ipsilateral threshold prolongation is more pronounced during lateralized migraine attacks. The results suggest dysfunctional visual perception is not limited to the migraine attack period, and a defective sensory processing/modulation in the visual pathways may involve the superior colliculus.

Three different short-interval intracortical inhibition methods in early diagnosis of amyotrophic lateral sclerosis.

Objectives: To compare the utility of conventional amplitude measurements of short-interval intracortical inhibition (A-SICI) with two threshold-tracking (T-SICI) methods, as aids to early diagnosis of amyotrophic lateral sclerosis (ALS). The new parallel threshold-tracking method (T-SICIp) was compared with the previously used serial tracking method (T-SICIs). Methods: 112 consecutive patients referred with the suspicion of ALS and 40 healthy controls were prospectively included. Based on clinical follow-up, patients were divided into 67 patients with motor neuron disease (MND) comprising progressive muscular atrophy (PMA) as well as ALS, and 45 patient controls. SICI was recorded from first dorsal interosseus muscle using the three different protocols. Results: MND patients had significantly reduced T-SICIp, T-SICIs and A-SICI, compared with healthy controls and patient controls, while healthy and patient controls were similar. Paradoxically, T-SICIp was least affected in MND patients with the most upper motor neuron (UMN) signs (Spearman ρ = 0.537, P < 0.0001) whereas there was no correlation for T-SICIs or A-SICI. T-SICIp also provided the best discrimination between patient controls and MND as determined by the receiver operating characteristic (ROC) curves. For patients with no UMN signs, area under ROC curve for 2-3ms inter-stimulus intervals was 0.931 for T-SICIp, 0.771 for T-SICIs and 0.786 for A-SICI. Conclusions: SICI is a sensitive measure for detection of cortical involvement in ALS patients. T-SICIp has higher sensitivity and specificity than T-SICIs and A-SICI, particularly in patients without any upper motor neuron signs.

Mirror neuron activity depending on the content and stage of the observed action: a TMS study.

Background/aim: The firing rate of the mirror neuron system in monkeys decreases systematically with more repetitions. The aim of this study is to investigate whether the activity of the mirror neuron system varies based on the observed movement and the contents of the action, as well as whether there is inhibition in the mirror neuron system when humans observe repeated actions. If inhibition is present, the second question of the study is whether it is related to the organization of the observed action. Materials and methods: Fourteen healthy volunteers participated in the study. Transcranial magnetic stimulation was applied to the left primary motor cortex and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous and abductor pollicis brevis muscles while the participants were watching videos specially prepared for the study. Results: There were no significant changes in MEP amplitudes compared to baseline MEPs while observing aimless action. However, while participants watched the repeated action video, the mean MEP amplitude increased at the beginning of the movement, but neither facilitation nor inhibition was detected when the participants watched the phase of grasping the object of the action compared to the baseline MEP amplitude. On the other hand, while participants were watching different activities, an increased MEP amplitude was observed at the beginning of the movement and in the grasping of the object of the action. Additionally, there was no significant reduction in MEP amplitude during any movement stages while observing the repeated action video. Conclusion: The findings of this study suggest that the activation of the mirror neuron system in humans depends on the content and stages of the observed movement. Additionally, there was no inhibition or systematic reduction in MEP amplitudes while watching a repeated action.

Feasibility and reliability of MScanFit motor unit number estimation in peroneus longus muscle.

INTRODUCTION/AIMS: Motor unit number estimation (MUNE) methods may be valuable to detect motor involvement earlier than compound muscle action potential (CMAP) amplitude. The most recent MUNE method, MScanFit, has been shown to have advantages compared with previously described methods. However, MScanFit has only been applied in a few lower extremity muscles. In this study we examined the feasibility and reliability of MScanFit in peroneus longus muscle. METHODS: Twenty healthy controls (16 males and 4 females; mean age, 36.05 ± 2.58 years) were examined twice within a 1- to 2-week interval. Fibular nerve was stimulated at the knee and CMAP scans were recorded from peroneus longus muscle. From this, MScanFit MUNE and size parameters were calculated, as was the CMAP amplitude. The reliability was examined using coefficient of variation (CV) and intraclass correlation coefficient (ICC). MUNE was correlated with CMAP amplitude using linear regression analysis. RESULTS: The CV between sessions was higher for CMAP amplitude (11.63 ± 1.88%) than MScanFit MUNE (3.13 ± 0.78%). Among the size parameters, mean unit amplitude (µV) showed the lowest CV (11.46 ± 1.77%). Using ICC, CMAP amplitude exhibited good reliability (0.787), whereas that of MScanFit MUNE was excellent (0.902). Reliability was good for all size parameters. There was no significant correlation between MScanFit MUNE and CMAP amplitude (R = 0.25, P > .05). DISCUSSION: MScanFit MUNE is feasible in the peroneus longus muscle, with high test-retest reliability in healthy subjects. Studies in patients are needed to examine the sensitivity of this muscle in disease.

Estimating the motor unit number of the flexor carpi ulnaris muscle with MScanFit MUNE.

INTRODUCTION/AIMS: MScanFit motor unit number estimation (MUNE) is a promising method for motor unit estimation and is reported to have good reliability in distal and small muscles. In this study, we investigated the reliability of MScanFit MUNE in a proximal forearm muscle, the flexor carpi ulnaris. METHODS: Twenty healthy volunteers were included in this study, and 15 participants were re-evaluated in a second session. The ulnar nerve was stimulated at the elbow and a compound muscle action potential (CMAP) scan from the flexor carpi ulnaris (FCU) muscle was recorded from each arm. CMAP, MUNE, and other motor unit parameters were obtained. Reproducibility was evaluated using intraclass correlation coefficients (ICCs). RESULTS: The average MUNE from 40 FCU muscles was 90.9 (standard deviation: 16.4). MScanFit MUNE and CMAP were not significantly different between the dominant and non-dominant sides. The ICC indicated good reliability between sessions for each side (0.81 and 0.8, respectively). DISCUSSION: Our results indicate that MScanFit MUNE is a feasible method with good reproducibility for MUNE of the FCU muscle.

Short latency afferent inhibition: comparison between threshold-tracking and conventional amplitude recording methods.

Short-latency afferent inhibition (SAI), which is conventionally measured as a reduction in motor evoked potential amplitude (A-SAI), is of clinical interest as a potential biomarker for cognitive impairment. Since threshold-tracking has some advantages for clinical studies of short-interval cortical inhibition, we have compared A-SAI with a threshold-tracking alternative method (T-SAI). In the T-SAI method, inhibition was calculated by tracking the required TMS intensity for the targeted MEP amplitude (200 uV) both for the test (TMS only) and paired (TMS and peripheral stimulation) stimuli. A-SAI and T-SAI were recorded from 31 healthy subjects using ten stimuli at each of 12 inter-stimulus intervals, once in the morning and again in the afternoon. There were no differences between morning and afternoon recordings. When A-SAI was normalized by log conversion it was closely related to T-SAI. Between subjects, variability was similar for the two techniques, but within-subject variability was significantly smaller for normalized A-SAI. Conventional amplitude measurements appear more sensitive for detecting changes within-subjects, such as in interventional studies, but threshold-tracking may be as sensitive as detecting abnormal SAI in a patient.

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.

Cortical plasticity causes useless hand syndrome in multiple sclerosis: a neurophysiological study in a rare case.

BACKGROUND: Useless Hand Syndrome (UHS) is a rare clinical manifestation of an upper cervical cord lesion, which is most commonly associated with multiple sclerosis (MS). The pathophysiological mechanism underlying UHS remains unclear. CASE: We report a 25-year-old woman, who described numbness in her left upper extremity. Cervical magnetic resonance imaging revealed a posterior upper cervical cord lesion. There was no cortical lesion that could explain the clinical findings. We measured (1) short-latency afferent inhibition (SAI) by obtaining motor evoked potentials as an indicator of sensorimotor integration and (2) somatosensorial temporal discrimination threshold (STDT) to display central somatosensory pathway function. In the right cerebral hemisphere, we found an excessive increase in STDT and no inhibition in the SAI paradigm. CONCLUSIONS: These findings indicate that impairment of sensorimotor integration and central processing of sensory stimuli cause useless hand syndrome.

Reduced Occipital Cortex Excitability in Amyotrophic Lateral Sclerosis.

PURPOSE: In addition to motor cortex involvement, sensory abnormalities have been demonstrated in amyotrophic lateral sclerosis (ALS), including structural and metabolic alterations in the occipital cortex. The aim of this study was to examine occipital excitability changes in ALS. METHODS: Twenty-one patients with ALS and 16 healthy subjects were enrolled into the study. Phosphene experience and phosphene threshold were studied to assess occipital excitability. Cognitive function was evaluated in both groups by means of Montreal Cognitive Assessment and Addenbrooke's Cognitive Examination-Revised visuospatial score tests. RESULTS: Phosphene was experienced in 13 (81.3%) healthy subjects and 9 (42.9%) patients with ALS ( P = 0.04). The mean phosphene threshold was not significantly different between the two groups. No correlation existed between phosphene threshold and motor cortical excitability parameters, ALS Functional Rating Scale Revised, Montreal Cognitive Assessment, and Addenbrooke's Cognitive Examination-Revised scores. CONCLUSIONS: Visual cortex is affected, and the occipital excitability is reduced in ALS, without any relation to motor cortical excitability changes, providing another clue suggestive of sensory involvement in ALS.

Cerebellar Transcranial Direct Current Stimulation Does Not Alter Somatosensory Temporal Discrimination Threshold.

This study aimed to explore the role of the cerebellum on the somatosensory temporal discrimination (STD) process. Twenty healthy volunteers were enrolled in the study. Each participant was included in three different transcranial direct current stimulation (tDCS) sessions as anodal, cathodal, and sham sessions in randomised order. Anodal and cathodal cerebellar tDCS (cTDCS) were given for 20 min at an intensity of 2 mA. The results of the study indicate no effect of cTDCS on STD. Although the study results show that cTDCS does not affect STD, because of the restricted sample size of the study, it is useful and necessary to investigate this relationship more in depth in a larger healthy subject population using different cTDCS methodologies.

Test-Retest Reliability of Short-Interval Intracortical Inhibition Assessed by Threshold-Tracking and Automated Conventional Techniques.

Two novel short-interval intracortical inhibition (SICI) protocols, assessing SICI across a range of interstimulus intervals (ISIs) using either parallel threshold-tracking transcranial magnetic stimulation (TT-TMS) or automated conventional TMS (cTMS), were recently introduced. However, the test-retest reliability of these protocols has not been investigated, which is important if they are to be introduced in the clinic. SICI was recorded in 18 healthy subjects using TT-TMS (T-SICI) and cTMS (A-SICI). All subjects were examined at four identical sessions, i.e., morning and afternoon sessions on 2 d, 5-7 d apart. Both SICI protocols were performed twice at each session by the same observer. In one of the sessions, another observer performed additional examinations. Neither intraobserver nor interobserver measures of SICI differed significantly between examinations, except for T-SICI at ISI 3 ms (p = 0.00035) and A-SICI at ISI 2.5 ms (p = 0.0103). Intraday reliability was poor-to-good for A-SICI and moderate-to-good for T-SICI. Interday and interobserver reliabilities of T-SICI and A-SICI were moderate-to-good. Although between-subject variation constituted most of the total variation, SICI repeatability in an individual subject was poor. The two SICI protocols showed no considerable systematic bias across sessions and had a comparable test-retest reliability profile. Findings from the present study suggest that both SICI protocols may be reliably and reproducibly employed in research studies, but should be used with caution for individual decision-making in clinical settings. Studies exploring reliability in patient cohorts are warranted to investigate the clinical utility of these two SICI protocols.

Gold Coast diagnostic criteria increase sensitivity in amyotrophic lateral sclerosis.

OBJECTIVE: This study evaluates diagnostic accuracy of the proposed 'Gold Coast' (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Five 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. RESULTS: Of 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). CONCLUSIONS: The simpler GC criteria increase the sensitivity, primarily due to considering PMA as a form of ALS with high specificity preserved. SIGNIFICANCE: This validation study supports that GC criteria should be used in clinical practice and may be used for inclusion in trials.