Selective and Inverse U-Shaped Curve Alteration of the Retinal Nerve in Amyotrophic Lateral Sclerosis: A Potential Mirror of the Disease

Introduction: Alterations in the visual pathway involving the retina have been reported in amyotrophic lateral sclerosis (ALS) but they lack consistency and subgroup analysis. We aimed to assess the retinal nerve fiber layer (RNFL) and retinal ganglion cells (RGCs) alterations in different stages of ALS patients and their association with ALS progression parameters.Methods: The study population consisted of 70 clinically diagnosed ALS patients and 55 age, sex matched controls. All of them underwent ophthalmic assessments and optical coherence tomography imaging. Four quadrants of the peripapillary RNFL and ganglion cell/inner plexiform complex (GCIP) were observed and automatically measured. Early-stage distal motor neuron axon dysfunction in ALS was detected by compound muscle action potential (CMAP) of the distal limbs within 12 months. The ALS disease parameters included the ALSFRS-R score and the disease progression rate (ΔFS).Results: Generally compared with controls, the nasal (p = 0.016) quadrant of the RNFL was thicker in ALS patients. When controlling for age and ΔFS, the RNFL(r = 0.37, p = 0.034) and GCIP(r = 0.40, p = 0.021) were significantly thickened as disease progressed within 12 months, while the RNFL declined with time after one year (r = −0.41, p = 0.037). ALS patients was subclassified into thickened RNFL (T-RNFL, >95th percentile of normal), impaired RNFL (I-RNFL, <5th percentile of normal) and normal RNFL. There were significant differences in the GCIP among the three groups (p < 0.001). In the T-RNFL group (n = 18), the RNFL was negatively correlated with the abductor pollicis brevis-CMAP amplitude within 12 months (r = −0.56, p = 0.01). Patients within 12 months in this group progressed faster than others (p = 0.039). In the normal RNFL group (n = 22), 13 patients were diagnosed beyond 12 months, whose ΔFS was remarkably lower (p = 0.007). In I-RNFL group (n = 30), the early stage patients (<12 months) had significant higher ΔFS (p = 0.006). One patient was with SOD1 pathogenic variant (p.A5V).Conclusion: Alterations of retinal nerve were not consistent in ALS patients with diverse phenotypes and progression rates. Generally speaking, the RNFL thickened during the first year and then gradually declined, which is related to but preceding the thickness change of the RGCs. Patients with a significant RNFL thinning in the early stage may have a faster progression rate. The inverse U-shaped curve transformation might be in accordance with early-stage motor neuron axonopathy.

Electrophysiological studies in patients with seropositive/seronegative myasthenia gravis

Background: Myasthenia gravis (MG) affects the neuromuscular transmission, causing fluctuating muscle weakness and fatigue. This study is carried out with the aim to study the electrophysiologic findings of different subtypes of MG referred to our center in Tehran, Iran. Methods: All patients with MG presenting to neurology department of Shariati Hospital, Tehran University of Medical Sciences were enrolled. Clinically, patients with MG were categorized as ocular vs. generalized. The acetylcholine receptor (Ach-R) and muscle-specific receptor tyrosine kinase (anti-MuSK) antibodies were performed. Repetitive Nerve Stimulation (RNS) was performed using the standard method, with supramaximal stimulation of muscles at the 3 Hz frequency by surface electrode at rest. Abductor pollicis brevis (APB) (median nerve), anconeus (radial nerve), trapezius (accessory nerve), and nasalis (facial nerve) muscles were studied in all patients. Single fiber electromyography (SFEMG) was performed by standard method. Results: 196 seropositive patients with MG were included in the study. In electrophysiological studies, RNS was performed for 146 patients of Ach-R-Ab positive MG, with positive results in 110 patients. In addition, SFEMG was conducted for 8 patients with negative RNS, which resulted in 7 positive tests.

Comparison of The Electrophysiological Characteristics of Tight Filum Terminale And Tethered Cord Syndrome

This study aims to characterize tight filum terminale (TFT) in motor evoked potential (MEP) testing by comparing TFT patients with both tether cord syndrome (TCS) patients and healthy subjects. Fifty TFT patients, 18 TCS patients, and 35 healthy volunteers participated in this study. We recorded MEPs following transcranial magnetic stimulation from the bilateral abductor hallucis muscles as well as compound muscle action potentials and F-waves evoked by electrical stimulation of the tibial nerve from the bilateral abductor pollicis brevis muscles. The peripheral conduction time (PCT) was calculated from the latency of the compound action potential and F-wave. Furthermore, the central motor conduction time (CMCT) was calculated by subtracting PCT from MEP latency. TFT and TCS patients had a significantly longer MEP latency than healthy subjects. PCT in TFT patients were significantly longer than those in TCS patients or healthy subjects. Using the cut-off values for PCT, we were able to diagnose patients with TFT patients with a sensitivity of 72.0% and a specificity of 91.4%. Prolonged PCT in the MEP test may be a useful indicator for TFT and suggests that MEP may be used as an adjunct diagnostic tool for TFT.

Role of Radiographs and Ultrasound in Diagnosing Calcific Tendinitis and Periarthritis in the Wrist and Hand with Ultrasound-Guided Barbotage as Management Tool

Aim To demonstrate the role of radiographs and ultrasound (USG) in the diagnosis of calcific tendinitis and periarthritis in the wrist and hand and the efficacy of USG-guided barbotage for its management. Materials and Methods A retrospective chart review was performed in six patients who presented with acute-onset pain in the wrist and hand varying from 3 days to 2 weeks. Four patients had tenderness over pisiform and two patients had pain along the lateral aspect of the wrist and thumb. Radiographs and USG revealed calcific focus corresponding to the site of pain. USG-guided calcific barbotage and injection was performed for the same and pain relief was assessed immediately and through telephonic follow-up at 6 months using subjective satisfaction score. Data were analyzed using Microsoft Excel 2013. Results Four patients with tenderness over pisiform had flexor carpi ulnaris calcific tendinitis and two patients with pain along the lateral aspect of the wrist and thumb had first metacarpophalangeal calcific periarthritis and abductor pollicis brevis calcific tendinitis on radiographs as well as USG. In post-USG-guided calcific barbotage and injection, all patients had significant immediate and 6 months delayed relief in symptoms with excellent satisfaction scores. Conclusion Acute calcific tendinitis/periarthritis is a benign and self-limiting inflammatory condition. Radiographs are extremely helpful in identifying calcific focus. Ultrasonography in experienced hands is the best modality to identify, confirm the symptomatic calcific focus, and perform USG-guided intervention. USG-guided calcific barbotage is the simplest, quickest, and effective way to treat this condition and avoid compromised functional capacity.

FEATURES ANALYSIS AND SYSTEM IDENTIFICATION OF MECHANOMYOGRAPHY AND ELECTROMYOGRAPHY UNDER TRANSCRANIAL MAGNETIC STIMULATION

Transcranial magnetic stimulation (TMS) is an electrophysiological technique that uses alternating magnetic fields to deliver electric current and stimulate the cerebral cortex. When TMS is used for the evaluation of brain diseases, it is necessary to detect the contraction of the corresponding muscles in the cerebral cortex stimulated by TMS, and the muscle activity referred to as motor evoked potential (MEP). This study simultaneously recorded the mechanomyography (MMG) and electromyography (EMG) from the right abductor pollicis brevis muscle during TMS with different intensities in order to observe whether the MEP parameters from MMG signals showed similar trait of EMG recordings. Moreover, the subspace method (N4SID) and transfer function were used to identify the TMS–MMG system. In this system, the input was a pulse signal of TMS, and the output was the MMG signal detected from the target muscle. The TMS–MMG system was identified as a fourth-order model. This study also analyzed the internal features of the system and demonstrated that the poles of healthy subjects were distributed in a range, and the gain increased with the increase of the TMS intensity. It was found that MMG signals can be used as diagnostic indicators of TMS, and the TMS–MMG model can be used to further explore the details of how TMS generates responses measured with MMG.

Expanding the Phenotypic Spectrum of ECEL1-Associated Distal Arthrogryposis

Distal arthrogryposis type 5D (DA5D), a rare autosomal recessive disorder, is caused by mutations in ECEL1. We describe two consanguineous families (three patients) with novel ECEL1 gene mutations detected by next-generation sequencing (NGS). A 12-year-old boy (patient 1) presented with birth asphyxia, motor developmental delay, multiple joint contractures, pes planus, kyphoscoliosis, undescended testis, hypophonic speech with a nasal twang, asymmetric ptosis, facial weakness, absent abductor pollicis brevis, bifacial, and distal lower limb weakness. Muscle MRI revealed asymmetric fatty infiltration of tensor fascia lata, hamstring, lateral compartment of the leg, and gastrocnemius. In addition, 17-year-old monozygotic twins (patients 2 and 3) presented with motor development delay, white hairlock, hypertelorism, tented upper lip, bulbous nose, tongue furrowing, small low set ears, multiple contractures, pes cavus, prominent hyperextensibility at the knee, hypotonia of lower limbs, wasting and weakness of all limbs (distal > proximal), areflexia, and high steppage gait. One had perinatal insult, seizures, mild intellectual disability, unconjugated eye movements, and primary optic atrophy. In the twins, MRI revealed extensive fatty infiltration of the gluteus maximus, quadriceps, hamstrings, and anterior and posterior compartment of the leg. Electrophysiology showed prominent motor axonopathy. NGS revealed rare homozygous missense variants c.602T > C (p.Met201Thr) in patient 1 and c.83C > T (p.Ala28Val) in patients 2 and 3, both localized in exon 2 of ECEL1 gene. Our three cases expand the clinical, imaging, and molecular spectrum of the ECEL1-mutation-related DA5D.

Home-based self-help telerehabilitation of the upper limb assisted by an electromyography-driven wrist/hand exoneuromusculoskeleton after stroke

Background Most stroke survivors have sustained upper limb impairment in their distal joints. An electromyography (EMG)-driven wrist/hand exoneuromusculoskeleton (WH-ENMS) was developed previously. The present study investigated the feasibility of a home-based self-help telerehabilitation program assisted by the aforementioned EMG-driven WH-ENMS and its rehabilitation effects after stroke. Methods Persons with chronic stroke (n = 11) were recruited in a single-group trial. The training progress, including the training frequency and duration, was telemonitored. The clinical outcomes were evaluated using the Fugl–Meyer Assessment (FMA), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), Motor Functional Independence Measure (FIM), and Modified Ashworth Scale (MAS). Improvement in muscle coordination was investigated in terms of the EMG activation level and the Co-contraction Index (CI) of the target muscles, including the abductor pollicis brevis (APB), flexor carpi radialis-flexor digitorum (FCR-FD), extensor carpi ulnaris-extensor digitorum (ECU-ED), biceps brachii (BIC), and triceps brachii (TRI). The movement smoothness and compensatory trunk movement were evaluated in terms of the following two kinematic parameters: number of movement units (NMUs) and maximal trunk displacement (MTD). The above evaluations were conducted before and after the training. Results All of the participants completed the home-based program with an intensity of 63.0 ± 1.90 (mean ± SD) min/session and 3.73 ± 0.75 (mean ± SD) sessions/week. After the training, motor improvements in the entire upper limb were found, as indicated by the significant improvements (P < 0.05) in the FMA, ARAT, WMFT, and MAS; significant decreases (P < 0.05) in the EMG activation levels of the APB and FCR-FD; significant decreases (P < 0.05) in the CI of the ECU–ED/FCR–FD, ECU–ED/BIC, FCR–FD/APB, FCR–FD/BIC, FCR–FD/TRI, APB/BIC and BIC/TRI muscle pairs; and significant reductions (P < 0.05) in the NMUs and MTD. Conclusions The results suggested that the home-based self-help telerehabilitation program assisted by EMG-driven WH-ENMS is feasible and effective for improving the motor function of the paretic upper limb after stroke. Trial registration ClinicalTrials.gov. NCT03752775; Date of registration: November 20, 2018.

Transcranial Magnetic Stimulation Following A Paired Associative Stimulation Protocol Based On A Videogame Potentiates Cortical Plasticity And Motor Behavior

BackgroundTranscranial Magnetic Stimulation (TMS) can induce synaptic plasticity potentiation following a paired associative stimulation (PAS) protocol, synchronizing a TMS single pulse with a movement task, named movement-related cortical stimulation (MRCS). However, MRCS plasticity induction and performance potentiation has been related exclusively to single movement tasks.MethodIn order to unveil the changes in motor learning produced by the MRCS protocol in complex movements, associated to Activities of Daily Living (ADL), we induced PAS changes in synchronization with a movement-related dynamic task by performing a customized videogame. We measured the task performance as well as nervous system excitability neuromodulation in 22 healthy subjects, analyzing Reaction Time (RT) and the peak-to-peak amplitude of the Motor Evoked Potentials (MEPs) respectively. The MEPs were recorded in the main task executor muscle, Abductor Pollicis Brevis (APB), and a secondary muscle, Abductor Digiti Minimi (ADM), before, right after, and 30 minutes after the intervention, in a real against sham group experimental parallel design. ResultsPAS application in synchronization with a complex task resulted in a motor performance potentiation effect, inducing shorter RTs when compared to the sham group. Moreover, it triggered long-term corticospinal plasticity mechanisms reflected in a MEP amplitude depression for the APB muscle at the higher intensity of recruitment curve and an enhancement of the corticospinal excitability of ADM muscle at around threshold intensity. RTs and ADM MEP amplitudes correlated positively in around threshold and high intensity assessments.ConclusionsWe conclude that the proposed PAS protocol facilitated the learning of time-accuracy movement in complex movement tasks, even if fatigue could be affecting the executor muscle excitability, and enhanced potentiation towards a passive muscle. This phenomenon can be very useful to develop neurorehabilitation strategies with complex movements (more similar to ADLs) and to avoid maladaptive plasticity related likely to fatigue.

A feasibility pilot study of the effects of neurostimulation on dysphagia recovery in Parkinson’s Disease

Introduction: Dysphagia often occurs during Parkinson’s disease (PD) and can have severe consequences. Recently, neuromodulatory techniques have been used to treat neurogenic dysphagia. Here we aimed to compare the neurophysiological and swallowing effects of three different types of neurostimulation, 5 Hertz (Hz) repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS and pharyngeal electrical stimulation (PES). Method: 12 PD patients with dysphagia were randomised to receive either 5 Hz rTMS, 1 Hz rTMS, or PES. In a cross-over design, patients were assigned to one intervention and received both real and sham stimulation. Patients received a baseline videofluoroscopic (VFS) assessment of their swallowing, enabling penetration aspiration scores (PAs) to be calculated for: thin fluids, paste, solids and cup drinking. Swallowing timing measurements were also performed on thin fluid swallows only. They then had baseline recordings of motor evoked potentials (MEPs) from both pharyngeal and (as a control) abductor pollicis brevis (APB) cortical areas using single-pulse TMS. Subsequently, the intervention was administered and post interventional TMS recordings were taken at 0 and 30 minutes followed by a repeat VFS within 60 minutes of intervention. Results: All interventions were well tolerated. Due to lower than expected recruitment, statistical analysis of the data was not undertaken. However, with respect to PAs swallowing timings and MEP amplitudes, there was visual separation in a positive direction between active and sham groups for all interventions. Conclusion: PES, 5 Hz rTMS and 1 Hz rTMS are tolerable interventions in PD related dysphagia. Due to small patient numbers no definitive conclusions could be drawn from the data with respect to individual interventions improving swallowing function and comparative effectiveness between interventions. Larger future studies are needed to further explore the efficacy of these neuromodulatory treatments in Parkinson’s Disease associated dysphagia.