Introduction/Aims
Age can affect hand muscles non‐uniformly. We investigated the influence of age on the compound muscle action potential (CMAP) amplitude of the hand muscles and the derived ...split‐hand index (SHI).
Methods
We studied 244 subjects investigated for suspected myasthenia gravis but without neuromuscular disorders. Abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) CMAPs were obtained by supramaximal stimulation at the wrist, recording with surface electrodes while checking the best recording site. We applied Tukey's HSD and Kruskal–Wallis one‐way analysis of variance for comparing age groups defined by median and interquantile ranges (IQRs). Spearman's rank correlation coefficient and linear regression were used for testing age‐dependence of measurements.
Results
Median age was 61.5 y (first IQR, 44.5; third IQR, 72.0; range 18–89). Age and neurophysiological measurements were similar between genders. APBCMAP, FDICMAP, ADMCMAP, and SHI were correlated with age (P < .001). Median and cutoff values were significantly different between age groups. APBCMAP, FDICMAP, and ADMCMAP decreased by 0.8/0.7/0.3 mV/y, respectively, and SHI decreased 0.15/y.
Discussion
The CMAP amplitudes of hand muscles and derived SHI were strongly age‐dependent, although this effect was less in ADM. This represents a physiological phenomenon. Future studies using the SHI should consider age effects.
Introduction/Aims
In amyotrophic lateral sclerosis (ALS), the role of spinal interneurons in ALS is underrecognized. We aimed to investigate pre‐ and post‐synaptic modulation of spinal motor neuron ...excitability by studying the H reflex, to understand spinal interneuron function in ALS.
Methods
We evaluated the soleus H reflex, and three different modulation paradigms, to study segmental spinal inhibitory mechanisms. Homonymous recurrent inhibition (H'RI) was assessed using the paired H reflex technique. Presynaptic inhibition of Ia afferents (H'Pre) was evaluated using D1 inhibition after stimulation of the common peroneal nerve. We also studied inhibition of the H reflex after cutaneous stimulation of the sural nerve (H'Pos).
Results
Fifteen ALS patients (median age 57.0 years), with minimal signs of lower motor neuron involvement and good functional status, and a control group of 10 healthy people (median age 57.0 years) were studied. ALS patients showed reduced inhibition, compared to controls, in all paradigms (H'RI 0.35 vs. 0.11, p = .036; H'Pre 1.0 vs. 5.0, p = .001; H'Pos 0.0 vs. 2.5, p = .031). The clinical UMN score was a significant predictor of the amount of recurrent and presynaptic inhibition.
Discussion
Spinal inhibitory mechanisms are impaired in ALS. We argue that hyperreflexia could be associated with dysfunction of spinal inhibitory interneurons. In this case, an interneuronopathy could be deemed a major feature of ALS.
Introduction/Aims
Fasciculations can be symptomatic, yet not progress to amyotrophic lateral sclerosis (ALS), a condition categorized as benign fasciculation syndrome (BFS). We aimed to assess ...electrodiagnostic changes and clinical course over time in patients with BFS.
Methods
This was a retrospective review of medical records of patients who were referred because of a suspicion of ALS or who had directly asked for a consultation because of a personal concern regarding ALS. All clinical and electromyography (EMG) investigations were performed by the same neurologist, following an established protocol. In addition, laboratory testing and imaging studies were performed as determined to be clinically necessary.
Results
We included 37 subjects (mean age 46 ± 14.7 y, 29 male, 7 healthcare professionals). Most patients had experienced fasciculations in both upper and lower limb muscles (62.2%); the remaining patients had fasciculations only in their lower limbs. EMG in seven subjects showed chronic neurogenic potentials in addition to fasciculation potentials; all of these were older men. Follow‐up data were available in 24 patients (median 4.7 y), 21 with repeat EMGs, including all those with neurogenic EMG changes at baseline (median 6.5 y). Two‐thirds of patients reported symptomatic improvement: 57.1% of those with abnormal EMG and 61.1% with normal EMG. The EMG changes were stable.
Discussion
Prognosis of BFS is favorable, regardless of minor EMG abnormalities. The latter do not necessarily imply progression to ALS.
Diagnostic delay in amyotrophic lateral sclerosis (ALS) is a relevant problem that has been investigated in different countries for a long time. This delay has impact on the number of unnecessary ...investigations, social and personal disease economic burden, anxiety levels related to uncertain medical decisions, and increased risk of needless surgeries. A wrongsurgery tends to further delay the diagnosis and to promote faster disease progression, a circumstance confirmed by neurologists dedicated to ALS and supported by scientific data. Additionally.adiagnosis delay decreasesthe chances of clinical trial participation. Shortening diagnostic delay has been the rational for establishing the Revised-El Escorial Criteria, the Awaji proposal (which is mainly focused on the neurophysiological features of ALS), and the Gold Coast Criteria. This demonstrates the importance of this subject, and the strong i nvo Ive m en to fdifferent institutionsandexpertsonimproving this constraint.
The change in distribution of TDP-43 causes dysfunction of RNA transport, transcription, and splicing. ...loss of nuclear TDP-43 leads to the inclusion of intronic sequences in mature RNA (ie, ...cryptic exons), causing premature polyadenylation, early stop codons, and transcript degradation.1 Brown and colleagues2 showed that TDP-43 dysfunction induces inclusion of a cryptic exon in UNC13A, causing UNC13A protein dysfunction. Campisi and colleagues identified an immune signature characterised by activated, antigen-specific CD8 T cells in the patients with ALS4, suggesting an activated immune response directed against unknown self-antigens of CNS origin.5 Mutations in the gene encoding superoxide dismutase 1 (SOD1) underlie about 2% of ALS cases, although this proportion is highly variable between countries. In a mouse model, antisense oligonucleotide treatment reduced the amounts of Fus in the CNS, delaying the loss of motor neurons.8 In one patient with ALS, intrathecal infusion of this antisense oligonucleotide caused a reduction of FUS expression in the CNS, decreasing FUS pathological burden and possibly slowing the disease progression rate.8 These findings lend hope for a potential new treatment approach for genetic-associated ALS.
Background and purpose
Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) ...and Q11 (orthopnoea) of the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS‐R). The association of respiratory test alterations with respiratory symptoms is unclear.
Methods
Patients with ALS and progressive muscular atrophy were included. We retrospectively recorded demographic data, ALSFRS‐R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100 ms, nocturnal oximetry (SpO2mean), arterial blood gases, and phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1, normal Q10 and Q11; G2, abnormal Q10; and G3, abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors.
Results
We included 276 patients (153 men, onset age = 62.6 ± 11.0 years, disease duration = 13.0 ± 9.6 months, spinal onset in 182) with mean survival of 40.1 ± 26.0 months. Gender, onset region, and disease duration were similar in G1 (n = 149), G2 (n = 78), and G3 (n = 49). Time to noninvasive ventilation (NIV) was shorter in G3 (p < 0.001), but survival was similar. ALSFRS‐R subscores were significantly different (G1 > G2 > G3, p < 0.001), except for lower limb subscore (p = 0.077). G2 and G3 patients were older than G1 (p < 0.001), and had lower FVC, MIP, MEP, PhrenAmpl, and SpO2mean. Independent predictors for G2 were MIP and SpO2mean; for G3, the only independent predictor was PhrenAmpl.
Conclusions
These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS‐R clinical relevance. Orthopnoea is a severe symptom that should prompt NIV, phrenic nerve response being an independent predictor. Early NIV promotes similar survival for G2 and G3.
Introduction
Immobility of the upper limbs has been associated with reduction of F‐wave frequency. However, there are no similar studies on lower limb (LL) F‐waves. We investigated the impact of LL ...rest on F‐wave and H‐reflex parameters.
Methods
The LLs of 14 healthy participants were studied after 90 minutes rest. F‐waves (frequency, latencies, chronodispersion, and mean amplitude) and H‐reflexes (latency and recruitment curve) were investigated bilaterally. In seven participants the protocol was repeated, but the temperature of one limb was reduced.
Results
Immobility only changed F‐wave latencies, which increased significantly (mean value of 2 ms, P < .01). Limb cooling did not influence results.
Discussion
Contrary to what occurred in cervical lower motor neurons (LMN), LL LMNs did not show a reduced F‐wave response to immobility, but their latency increased significantly. This could have been due to reduced Renshaw inhibition of small LMNs, thus facilitating their response to antidromic stimulation and causing delayed late responses.
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper motor neurons in the motor cortex and lower motor neurons (LMN) in the brainstem and spinal cord, resulting in a ...progressive functional impairment. Neurophysiology is a diagnostic tool to detect dysfunction of upper motor neurons and LMN, even when the changes are subclinical. Electromyography is the standard neurophysiological investigation to detect LMN changes, which is essential to exclude mimicking disorders and attain early diagnosis. Recently, Awaji criteria was proposed to support ALS diagnosis, in these criteria fasciculation potentials associated with neurogenic motor unit potentials represents a sufficient marker of LMN involvement, in each muscle. Many studies have confirmed that Awaji criteria are more sensitive, permitting earlier diagnosis without loss of specificity when compared with the revised El Escorial criteria. Fasciculations are easily detected by ultrasound; increasingly, this technique has been used to diagnose ALS, combined with electromyography. This combination can increase diagnostic accuracy. Many techniques for estimating the number of motor units have been proposed, they are useful to quantify LMN loss. Electrical impedance myography is an emerging technique with great potential to monitor ALS progression. Neurophysiological investigation of upper motor neuron dysfunction is difficult in ALS, detecting decreased cortical inhibition by threshold tracking cortical magnetic stimulation is a promising method, which needs to be validated in different centers.
Background and purpose
Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). The impact of diabetes mellitus (DM) on respiratory function ...of ALS patients is uncertain.
Methods
A retrospective cohort study was carried out. From the 1710 patients with motor neuron disease followed in our unit, ALS and progressive muscular atrophy patients were included. We recorded demographic characteristics, functional ALS rating scale (Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised ALSFRS‐R) and its subscores at first visit, respiratory function tests, arterial blood gases, phrenic nerve amplitude (PhrenAmpl), and mean nocturnal oxygen saturation (SpO2mean). We excluded patients with other relevant diseases. Two subgroups were analysed: DIAB (patients with DM) and noDIAB (patients without DM). Independent t‐test, χ2, or Fisher exact test was applied. Binomial logistic regression analyses assessed DM effects. Kaplan–Meier analysis assessed survival. p < 0.05 was considered significant.
Results
We included 1639 patients (922 men, mean onset age = 62.5 ± 12.6 years, mean disease duration = 18.1 ± 22.0 months). Mean survival was 43.3 ± 40.7 months. More men had DM (p = 0.021). Disease duration was similar between groups (p = 0.063). Time to noninvasive ventilation (NIV) was shorter in DIAB (p = 0.004); total survival was similar. No differences were seen for ALSFRS‐R or its decay rate. At entry, DIAB patients were older (p < 0.001), with lower forced vital capacity (p = 0.001), arterial oxygen pressure (p = 0.01), PhrenAmpl (p < 0.001), and SpO2mean (p = 0.014).
Conclusions
ALS patients with DM had increased risk of respiratory impairment and should be closely monitored. Early NIV allowed for similar survival rate between groups.
