Search

Objective To explore the diagnostic accuracy of the split-hand index (SHI) for amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) using sonographic assessment of muscle thickness. Methods We performed a prospective sonographic assessment of hand muscle thickness in 59 controls, 87 patients with ALS, and 33 patients with SMA. We determined the diagnostic accuracy of SHI for differentiating patients with ALS and SMA from controls. Results Patients with ALS and SMA had significantly lower muscle thickness and SHI values compared with controls. SHI showed excellent diagnostic accuracy for differentiating ALS from controls, and good diagnostic accuracy for differentiating SMA from controls. Conclusions SHI determined by sonographic measurement of hand muscle thickness seems to be a promising tool for the diagnosis of ALS and may be added easily when performing neuromuscular ultrasound. Significance SHI determined by sonographic measurement of hand muscle thickness can differentiate between healthy subjects and patients with ALS and SMA.

Objective There is still insufficient knowledge about natural history in adult spinal muscular atrophy, thus valid markers for treatment and disease monitoring are urgently needed. Methods We 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. Results Denervation 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. Conclusion We 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. Significance Our data show the power of the MUNIX method as a biomarker for upcoming questions in adult SMA.

This study was to apply the newly developed electrical impedance myography (EIM) technique to examine hand muscles in patients with an incomplete cervical spinal cord injury (SCI).EIM was performed on the thenar, hypothenar, and first dorsal interosseous (FDI) muscles of SCI (n=16) and age-matched healthy control (n=18) subjects. By sending low intensity and high frequency current through the skin and measuring the consequent voltage, EIM estimates the major impedance parameters, which include resistance (R), reactance (X) and phase angle (θ).The SCI group had lower reactance and phase angle (p0.0001) as compared to the control group in all three muscles, and lower resistance in the thenar muscle (p0.05). The SCI group also demonstrated a smaller anisotropy in resistance (p0.0001) and larger anisotropy in phase angle (p0.05) compared to those from healthy controls.The reduced reactance and phase angle of paralyzed muscles could be due tochanges of membrane integrity and fat infiltration, whereas the change in the anisotropy may reflect the rearrangement of muscle fiber geometry.The EIM provides a quick and convenient tool for examination of muscle alterations after SCI.

Objective C8-dominant innervation of ulnar-innervated and T1-dominant innervation of median-innervated intrinsic hand muscles have been suggested, although less is known regarding forearm muscles. We aimed to determine myotomal innervation of the forearm muscles based on the clinical and electromyographial findings of patients with C8 or T1 lesions. Methods Medical Research Council scale and EMG findings were retrospectively reviewed in 16 patients with C8 lesions (2 postmedian sternotomy C8 plexopathy and 14 C8 radiculopathy) and 9 patients with T1-dominant lesions (8 true neurogenic thoracic outlet syndrome and 1 T1 radiculopathy). Results Clinical and EMG findings revealed T1-dominant innervation of the flexor digitorum superficialis, flexor digitorum profundus of the index finger, abductor pollicis brevis, and flexor pollicis longus muscles, and C8-dominant innervation of the flexor carpi ulnaris, flexor digitorum profundus of the little finger, and digit extensors innervated by the posterior interosseous nerve. The first dorsal interosseous, and abductor digiti minimi muscles seem to be innervated by both C8 and T1 roots. Conclusions C8-dominant innervation of ulnar-innervated muscles and T1-dominant innervation of median-innervated muscles are also evident for forearm flexor muscles. Significance Such an additional evidence for myotomal innervation will improve localization in clinical as well as electrophysiological diagnoses.

Introduction Transcranial magnetic stimulation (TMS) can be used to map the corticomotor representations of hand muscles in the precentral gyrus. The spatial peak of the corticomotor representations is often not located in the primary motor hand area (M1HAND), but shows an anterior shift towards the caudal part of dorsal premotor cortex (PMd). Here we used magnetic resonance imaging (MRI) to test the hypothesis that the “hand knob” of the precentral gyrus shows different structural properties in individuals with a clear “premotor” representation compared to individuals with a preponderant “primary-motor” representation of hand muscles. Methods Twenty-four volunteers (mean age: 24.3 ± 0.9 SE, 12 women) underwent whole-brain structural MRI and sulcus-shape based TMS mapping of the right precentral gyrus. High-resolution T1-weighted MRIs were used for neuronavigation of TMS and to calculate regional cortical thickness of the precentral gyrus. We also performed quantitative multiparameter mapping of the longitudinal relaxation rate (R1 = 1/T1) as an index of cortical myelination and simulated the electric field strength induced by TMS at motor threshold (—E—) in the hand-knob region (SimNIBS software). Sulcus-shape based TMS mapping was used to obtain mediolateral and posterior-anterior corticomotor excitability profiles of the left abductor digiti minimi and first dorsal interosseus muscles. Results In 14 out of 24 individuals (58%), TMS mapping disclosed a clear spatial peak in the PMd (referred to as “PMd” subjects”), whereas the remaining 10 subjects (42%) showed maximal motor responses more posteriorly in M1HAND (referred to as M1HAND subjects). Motor threshold was not different between the two groups (p = 0.265). Compared “PMd” subjects, “M1” subjects displayed a higher electric field strength in the very rostral part of the M1HAND in the transition zone from the wall to the crown of the precentral gyrus (p = 0.01). In addition, “PMd” subjects showed an overall increase of regional myelination in the precentral gyrus relative to the “M1” subjects (mixed model ANOVA: F(1,18) = 5.362, p = 0.033). No difference between two groups was evident for curvature and cortical thickness. Conclusion Differences in location of the “motor hot spot” are associated with differences in microstructure in the precentral gyrus and the magnitude of the induced electrical field. The results support the notion of two distinct functional and microstructural phenotypes of corticomotor hand representations in human precentral gyrus. They also underscore the usefulness of electrical field modelling to account for inter-individual differences in the biophysiological effects of TMS in the human brain.

The aim of the present study was to assess whether peripheral mechanisms, mediated through axonal dysfunction, may contribute to development of the split-hand in amyotrophic lateral sclerosis (ALS).Median and ulnar nerve motor axonal excitability studies were undertaken on 21 ALS patients with motor responses recorded over the abductor pollicis brevis (APB), abductor digit minimi (ADM) and first dorsal interosseous (FDI) muscles, and results compared to 24 controls.The split-hand index (SI), an objective biomarker of preferential atrophy of APB and FDI muscles, was significantly reduced in ALS (SI(ALS) 7.8 ± 1.7, SICONTROLS 13.1 ± 1.1, P0.0001). Axonal excitability studies identified significant prolongation of strength-duration time constant in ALS patients when recording over the APB (P0.05) and ADM axons (P0.05) but not FDI axons (P=0.22). Greater changes in depolarising threshold electrotonus were also evident across the range of intrinsic hand muscles and were accompanied by increases of superexcitability in APB (P0.01) and FDI (P0.05) axons.The present study reinforces the significance of the split-hand phenomenon in ALS and argues against a significant peripheral contribution in the underlying development.Axonal dysfunction may appear as a downstream process that develops secondary to the intrinsic pathophysiological origins of ALS.

Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. Very surprisingly, however, it is still unclear which part of M1 is stimulated by TMS when a muscle twitch is elicited. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. I will report on two recent studies which combined electrophysiological measurements of muscle responses to TMS with realistic estimates of the induced electric field, based on the finite-element method (FEM) and MRI-derived individual head models. In the first study, the orientation of a standard figure 8 coil was systematically varied and the field changes in different subparts of the motor cortex were compared with the electrophysiological threshold changes. In the second study, three figure 8 coils having different field decays were used and the differences in the electrophysiological thresholds were correlated with the differences in the calculated field distributions. Both studies consistently demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our studies are one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for two hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.

Objective To investigate inter-individual variation in the efficiency of magnetic brainstem stimulation (BST) with regard to the stimulation site. Methods We studied 31 healthy subjects, using a right hand muscle as a recording site. Three stimulation sites were compared: BST over the inion (inion BST), and BST over the midpoint between the inion and the right (ipsilateral BST) or left (contralateral BST) mastoid process. Five suprathreshold BSTs were performed for each stimulation site using the same stimulation intensity. The mean peak-to-peak amplitudes of motor evoked potential (MEP) were compared. The active motor threshold (AMT) and onset latency for inion BST and ipsilateral BST were also measured and compared. Results Contralateral BST did not evoke discernible MEPs in most subjects. In 21 subjects (67.7%), ipsilateral BST elicited larger MEPs than inion BST did, and AMT for ipsilateral BST was lower than or equal to the AMT for inion BST in all subjects. Ipsilateral BST elicited shorter latency in such subjects. Conclusions The suitable stimulation site for BST differed among subjects. About two-thirds showed larger MEP to ipsilateral BST. Significance These findings might help us to find an efficient stimulation site for BST in each subject.

TMS can be used to map the corticomotor representations of hand muscles (HMs) in the precentral gyrus (PG), whose spatial peak is often not located in the primary motor hand area (M1HAND) but shifts towards the caudal part of dorsal premotor cortex (PMd). We used magnetic resonance imaging (MRI) to test the hypothesis that “hand-knob” of PG shows different structural properties in individuals with a “premotor” representation compared to individuals with a “primary-motor” representation of HMs. Twenty-four volunteers underwent MRI and sulcus-shape-based TMS-mapping of right PG. T1-weighted-MRIs were used for neuronavigation and to calculate cortical-thickness of the PG. We also performed quantitative multiparameter mapping of the longitudinal relaxation rate as an index of cortical myelination and simulated the electric field strength induced by TMS in the hand-knob-region. In 14 out-of 24 individuals (58%), TMS mapping disclosed a spatial peak in the PMd (“PMd-subjects”), whereas the remaining 10 subjects (42%) showed maximal motor response in M1HAND (“M1HAND-subjects”). “M1-subjects” displayed a higher electric field strength in the rostral part of the M1HAND (p = 0.01). “PMd-subjects” showed an increase of regional-myelination in the PG (p = 0.033). The results support the notion of two distinct functional-microstructural phenotypes of corticomotor hand representations in human PG.

Regaining the function of an impaired limb is highly desirable in individuals experiencing paralysis. One possible avenue to achieve this goal is through rewiring of preserved neural structures to bridge the interrupted pathway using a brain-computer interface. Here we demonstrated that monkeys with subcortical stroke were able to learn to use an artificial cortico-muscular connection (ACMC), brain-controlled functional electrical stimulation to the hand muscles, to regain volitional control of a paralyzed hand. In a targeted manner, the ACMC induced reorganization of cortical activities among an extensive cortical area; the modulating high-gamma activity became concentrated around an arbitrarily selected cortical site controlling stimulation to the muscles. This reorganization could be reset and rapidly reorganized to a new cortical site. Thus, the ACMC imparted a new function for muscle control to a connected cortical site and triggered cortical reorganization in order to restore impaired motor function after stroke.

Introduction The aim of this study is to compare repeater F-wave parameters with CMAP amplitudes recorded from the hand muscles (as indicators of the amount of lower motor neuron [LMN] loss) and with the triple stimulation technique (TST) ratios in the same muscles (as indicators of upper motor neuron [UMN] involvement) in 19 patients with amyotrophic lateral sclerosis (ALS). Methods Ninety F-waves were recorded from thenar and hypothenar muscles by supramaximal stimuli applied to the relevant nerves at the wrist level. Repeater F-waves (Frep) were visually defined as those presented with the same amplitude, latency and shapes. Repeater neuron (RN) index, Frep index, persistances of F-waves, F/M amplitude ratio and the neurophysiologic index (NI) were calculated. By depending our laboratory normals, TST ratio values lower than 82% and 86% were accepted as abnormal showing UMN involvement in thenar and hypothenar muscles respectively. Results TST ratios were abnormal in 13 thenar and 11 hypothenar muscles. None of the Frep parameters showed any significant relationship with the abnormal TST ratios, except the lower Frep index in thenar muscles, in patients with UMN involvement according to low TST ratios. However, there was a strong negative correlation with the CMAP amplitudes and Frep index and RN index values in hypothenar muscle (Spearman’s rho, p Conclusion These findings imply that repeater F waves might be a manifestation of LMN loss more than being a result of UMN involvement.

Objectives Repeater F-waves (Freps) were seen in patients with amyotrophic lateral sclerosis (ALS). The factors implicated for the presence and frequency of Freps were loss of the motor neurons and the changes in their excitability. The aim of this study was to assess the Freps in ALS patients and to compare their frequencies in thenar and hypothenar muscles. Methods Sixteen ALS patients and 11 healthy controls were recruited to the study. All patients had ⩾2 mV CMAPs recorded from the hand muscles. Ninety F-waves were recorded from abductor digiti minimi (ADM) and abductor pollicis brevis (APB). The index of repeater neurons (RN) and Freps were calculated. Results Mean index RN and index Freps values of ADM and APB muscles in ALS group (17.1 and 42.6 for ADM and 16.3 and 41.9 for APB) were significantly higher than those of healthy controls (4.7 and 13.9 for APB and 1.5 and 3.6 for ADM). ALS group had a lower persistence of F-waves for both muscles than healthy controls (56.4 and 94.6 for APB and 83.4 and 97.0 for ADM). Freps parameters were not different between thenar and hypothenar muscles, whereas persistence of F-waves was lower in the thenar (56.4%) as compared to the hypothenar (83.4%) muscles. Discussion Similar Freps parameters in the thenar and hypothenar muscles might be caused by the inclusion criteria. Lower F-persistence in the thenar muscles was in accordance with the split-hand phenomenon. Conclusion The assessment of Freps and F persistence may be useful in understanding of the electrophysiological changes in ALS.

Objective We aimed to characterize changes in motor cortex function in Asperger’s syndrome (AS) with MRI-navigated TMS and related abnormalities in fine motor skills. Methods Eight boys with AS (aged 8–11 years) and eight neurotypical controls were studied. Resting motor threshold and motor-evoked potentials were determined for abductor pollicis brevis (APB) muscle. Functional motor areas for six hand muscles (APB, ADM, FDI, FCR, ECR and BB) were mapped at 110% of rMT. Center of gravities of representations and the sizes of representation areas were determined. Both hemispheres were studied. Manual dexterity was assessed by Box and Block Test. Results AS boys had larger arm/hand ratio in left hemisphere ( p = 0.010) and larger left/right ratio for arm ( p = 0.014) than controls. Other TMS-related measures were similar between the groups. AS boys also had poorer manual dexterity than controls ( p = 0.005). Arm/hand representation ratio in the left hemisphere (Spearman’s correlation coefficient − 0.528, p = 0.036) and left/right arm representation ratio (−0.760, p = 0.001) correlated negatively with manual dexterity. Conclusions Sizes of upper arm representation areas are altered in AS and they correlate with fine motor skills. Key message Changes in motor cortex function may partly explain abnormalities and impairments in fine motor skills among children with AS.

Objective Preferential wasting of the thenar group of intrinsic hand muscles including the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) termed the split-hand sign, has been described as a specific feature of Amyotrophic Lateral Sclerosis (ALS). Greater corticomotorneuronal input to the thenar intrinsic hand muscles has been proposed as one of the pathophysiological mechanisms underlying the split hand sign and consequently difference in cortical excitability between the thenar and hypothenar intrinsic hand muscles was assessed in the present study, in a group of ALS patients and age matched healthy controls. Methods Cortical excitability was recorded using the threshold tracking transcranial magnetic stimulation (TMS) technique from the APB, FDI and abductor digiti minimi (ADM) muscles in 26 Awaji Criteria possible/probable ALS patients (17 male; 9 female; mean age 58.6 ± 1.9 years. Results were compared with 21 age matched healthy controls. Results Short interval intracortical inhibition (SICI) was globally reduced ( P P Conclusion There is a global increase in cortical excitability in ALS, further characterised by a preferential increase in cortical excitability of the APB and FDI muscles, which may underlie the clinical development of the ALS split-hand sign.

Introduction Conversion paralysis (CP) concerns patients with unintentional neurological symptoms (i.e. paralysis) which are present without a neurological explanation. Neuroimaging research shows that abnormal cerebral activity accompanies conversion paralysis. Previously, a positive effect of repetitive transcranial magnetic stimulation (rTMS) in CP was reported (Schonfeldt-Lecuona et al., 2006) after 110% motor threshold (MT) stimulation. To avoid a psychological effect of thumb movement, we stimulated below MT (80%). Objective Does rTMS treatment decrease symptoms in conversion disorder? Methods 10 subjects (three male, 34–65years old) with CP of the hand were admitted to the hospital for two weeks, with the exception of weekends and received rTMS over the contralateral motor cortex (hand area) during 30min, 2 times 5days, once a day (15Hz, 300×2s trains, intensity 80% of motor threshold). Illness duration varied between 4weeks and 25years. 6 out of 10 patients were additionally included in a sham condition. Before the first session and after the last session, we monitored strength of the hand muscles using dynamometry and subjective patients' ratings. A Wilcoxon signed-rank test was used to compare muscle strength before and after rTMS. Preliminary results A Wilcoxon Signed Ranks Test showed a significant effect of rTMS ( Z =−2.803, p =0.005). Indeed, median muscle strength before rTMS was 36.5Newton, median muscle strength after rTMS was 64Newton. In contrast, only 2 patients showed improvement in the sham condition, 3 out of 6 patients showed no improvement after sham rTMS and 1 patient showed reduced muscle strength. The median muscle strength pre-and post-sham rTMS was 42.5 and 34.5Newton. The subjective patient's rating did not match these results, only 2 patients reported subjective improvement of the function of their hand after rTMS. Conclusion These results confirm that 80% rTMS is an effective method to increase muscle strength in patients with conversion paralysis. Its effect does not rely on psychological components such as visible thumb movement.