Nerve In Amyotrophic Lateral Sclerosis Research Articles

Neuromuscular Phrenic Nerve Ultrasound versus Nerve Conduction Study of Phrenic Nerve in Amyotrophic Lateral Sclerosis

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that is, characterized by progressive loss of the upper (UMNs) and lower motor neurons (LMNs) at the spinal or bulbar level. In the most advanced stages, ALS patients will develop symptoms of dyspnea due to weakness of respiratory muscles and subsequently death in ALS. Objective To compare between neuromuscular ultrasound and nerve conduction study of phrenic nerve in the assessment of pulmonary function in Amyotrophic lateral sclerosis patients. Patients and Methods This was a case control study performed in Ain Shams University Hospitals in the period from 2/2022 to 8/2022. The study included 15 patients diagnosed with Amyotrophic lateral sclerosis according to El Escorial revised criteria and 15 healthy people served as controls. Patients were randomized by a simple computer generated method into two groups: A study group (n = 15) and a control group (n = 15). Results This study showed that PNCS is more sensitive than CSA in the assessment of respiratory affection in ALS. PNCS is simple and easy to do and doesn’t need a highly equipped device. Also PN amplitude has a normal value and many studies were done about it. To our knowledge no research studies this correlation between PN CSA and PN amplitude in the assessment of respiratory affection among ALS patients. Conclusion Electrodiagnosis and Neuromuscular ultrasound have a valuable role in the diagnosis and monitoring ALS patients. This study showed that PNCS is more sensitive than PN CSA by NMUS in the assessment of respiratory affection in ALS. PNCS is simple and easy to do and doesn’t need a highly equipped device. Also there were well established reference values as many researches studied electrophysiology of phrenic nerve.

The cross-sectional area of peripheral nerve in amyotrophic lateral sclerosis: A case-control study

ObjectiveA growing body of literature recognises the importance of peripheral nerve ultrasound in neuromuscular disorders. Several attempts have been made to differentiate amyotrophic lateral sclerosis (ALS) from multifocal motor neuropathy (MMN) using peripheral nerve ultrasound. A much-debated question is whether the cross-sectional area (CSA) of peripheral nerve in ALS patients is significantly smaller compared to healthy controls. This study aims to determine the CSA of peripheral nerves in patients with ALS. MethodsOne hundred and thirty-nine patients with ALS and 75 healthy controls were recruited. Ultrasound of the median, ulnar, and trunks of the brachial plexus and cervical nerve roots was undertaken in ALS patients and controls. ResultsCompared to controls, ALS patients had mild reductions of the median nerve, most sites of the ulnar nerve, trunks of the brachial plexus and cervical nerve roots. Another important finding of this study is that the median nerve tends to have a more significant reduction than the ulnar nerve in ALS patients, especially at the proximal. ConclusionsUltrasound could be sensitive to nerve motor fibre loss in patients with ALS. CSA at the proximal Median nerve may be a promising biomarker in patients with ALS.

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.

P231 High resolution ultrasound of peripheral nerves in amyotrophic lateral sclerosis

Introduction In this study we examined whether the ultrasound (UL) measurement of median and ulnar nerves are different in ALS patients compared with healthy subjects(HS) and whether US can be used to demonstrate the progressive axonal loss by showing decrease in cross-sectional area (CSA) of the nerves. Methods We included fifty-eight patients, all suspected of either ALS, polyneuropathy or myopathy. We measured the CSA of the median and ulnar nerve at brachial and antebrachial level, bilaterally. We calculated inter nerve and intra nerve ratio for both nerves. Fifteen were later diagnosed with ALS thus included and invited to follow-up examination 3 months later. Only nine patients showed up to follow up. We recruited a control group of 38 HS. Results We found no difference in mean CSA of the median nerve and ulnar nerve at the brachial and antebrachial level between ALS patients and HS. We found an increase of mean CSA of both nerves at the antebrachial level at three month follow up, median nerve baseline 0.053 (0.017), median nerve follow-up 0.068 (0.016); p = 0.01, ulnar nerve baseline 0.044 (0.017), ulnar nerve follow-up 0.050 (0.017); p = 0.048. Conclusion CSA of the peripheral nerves could not differentiate the ALS group from the HS. At follow up, we found an unexpected increase of the CSA in ALS patients. Significance An inflammatory process secondary to axonal loss could be the explanation for the increase of the nerve CSA. Further and larger studies studies are needed to confirm this hypothesis.

Involvement of distal sensory nerves in amyotrophic lateral sclerosis.

The diagnostic criteria for amyotrophic lateral sclerosis (ALS) require normal sensory nerve conduction studies (NCS) or abnormal NCS only in the presence of neuropathy of identified etiology. In this study, we investigated the presence and extent of involvement of Aß sensory fibers in ALS. Distal sensory NCS [antidromic dorsal sural (DS) and orthodromic medial plantar (MP)] and conventional sensory NCS (unilateral median sensory and bilateral sural nerves) were performed in 16 definite and 2 probable ALS patients (based on Awaji criteria) and 31 controls. Abnormal conventional sensory NCS were found in 8 (44.4%) ALS patients and 1 (3.2%) control subject (P = 0.002), whereas abnormal distal sensory NCS were found in 12 (66.7%) ALS patients and 3 (9.6%) controls (P < 0.0001). Distal sensory NCS were more often abnormal than conventional sensory NCS in ALS. Muscle Nerve 54: 1086-1092, 2016.

Sonographic evaluation of cervical nerve roots in ALS and its clinical subtypes.

Morphological assessment of peripheral nerves in amyotrophic lateral sclerosis (ALS) has been available by sonography. Detection of possible axonal atrophy could be important in predicting progression. Research on correlation between sonographic findings and clinical presentation has been sparse. The aim of the study was to assess possible motor axon loss in patients with ALS by sonography and to correlate the imaging features with clinical subtypes. Patients with either definite or probable ALS and control subjects had sonographic evaluation of the cervical nerve roots (C5, C6, and C7). Each diameter and their sums were measured. The ALS patients were classified by their clinical onset and progression (arm-onset, leg-onset, bulbar, and flail-arm variant) and the sonographic features were compared. Overall, the cervical nerve roots were thinner in ALS than in the controls, but the diagnostic sensitivity was low. The patients with arm dysfunctions tended to show thinner nerve roots than those with normal or relatively preserved arm functions. The four ALS subtypes showed similar diameters of the nerve roots. There was no correlation between the disease duration and the diameters of the nerve roots. Sonography of the cervical nerve roots showed axonal atrophy in ALS and potentially reflects subtle arm dysfunctions.

PO1.21 Neurophysiological Index Applied at Posterior Tibial Nerve in Amyotrophic Lateral Sclerosis: Comparison with Amyotrophic Lateral Sclerosis Functional Rating Scale

PO1.21 Neurophysiological Index Applied at Posterior Tibial Nerve in Amyotrophic Lateral Sclerosis: Comparison with Amyotrophic Lateral Sclerosis Functional Rating Scale

Transcranial magnetic stimulation of motor pathways directed to muscles supplied by cranial nerves in amyotrophic lateral sclerosis

Objectives: In amyotrophic lateral sclerosis (ALS), transcranial magnetic stimulation (TMS) detects remarkable abnormalities of central motor circuits: cortical excitability threshold, silent period (SP) duration and intra-cortical inhibition. TMS directed to cranio-facial musculature was performed in ALS patients in order: (1) to document the neurophysiological involvement of motor central and peripheral cranial pathways by evaluating changes of threshold and SP; (2) to discover a possible correlation between the clinical picture and abnormal excitability properties.Methods: Motor evoked potentials (MEPs) were recorded from masseter, genioglossus and orbicularis oris muscles of both sides in 25 ALS patients and 25 controls, in response to TMS delivered over the face M1 area and the vertex.Results: TMS gave rise to two orders of responses: bilateral MEPs during contraction represented the central responses, and motor action potentials (MAPs) during rest represented the peripheral responses. MEPs were followed by SPs, which increased linearly with increasing TMS intensity (r=0.8). At least one of the analyzed parameters was abnormal in all patients: central abnormalities (increased active threshold, delayed MEPs, reduced SP) were found in 96% of patients, alone or combined with abnormalities of the MAPs (reduced area and/or prolonged latency). The reduction of SP was linearly related to the Norris score (r=0.95).Conclusions: Our study shows that TMS is able to detect the involvement of multiple cranial muscles in ALS. This finding offers often pre-clinical information about the disease picture. Therefore, it can be employed as a valuable means for early diagnosis.

Somatosensory evoked potentials elicited by stimulation of lower-limb nerves in amyotrophic lateral sclerosis

To determine lower limb somatosensory modifications in amyotrophic lateral sclerosis (ALS), we studied somatosensory evoked potentials (SEPs) elicited by stimulation of tibial posterior nerves (TP), sural nerves (SN), saphenous internous nerves (SA), and medial plantar nerves (PL) of both limbs in 24 ALS patients, and compared the results with those from 17 normal subjects. Responses were recorded according to the international 10–20 system. Normal sensory conduction velocities of SN, SA and PL and H reflexes in soleus muscles were prerequisites for patient inclusion in this study. The results showed marked alterations in SEPs cortical components of all lower limb nerves, which could be related to abnormal sensory transmission (after spinal N22), or cortical abnormalities. We put forward the hypothesis of impairment of pyramidal control of the sensory system and Clark's column involvement to explain such anomalies. It was concluded that SEPs abnormalities in the lower limbs are a common feature in ALS.

Changes of unmyelinated nerve fibers in sural nerve in amyotrophic lateral sclerosis, Parkinson’s disease and multiple system atrophy

Quantitative changes in unmyelinated nerve fibers (UMNFs) of sural nerves in patients of amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and multiple system atrophy (MSA) were evaluated using autopsy materials whose pathological diagnosis had been confirmed by careful postmortem examinations. Ordinary ALS cases demonstrated no involvement in cutaneous UMNFs; however, the patients with long survival due to the application of ventilatory support showed bimodality in UMNF diameter histograms, and a patient with involvement of systems other than motor pathways showed an abnormal value in two indices: a low percentage of subunits containing axon(s) and a high mean number of Schwann cell profiles per axon. A significant reduction of the mean value of UMNF density (21%) was found in PD patients. Because the density of myelinated nerve fibers did not show any significant decrease as compared with age-matched controls, the change of nerve fibers in peripheral nervous system was considered to be confined to UMNFs in PD. Elderly PD cases showed enhanced changes in the ageing process, as expressed by the two indices described above. In MSA, the mean value of UMNF density was significantly decreased (23%), and this decrease almost paralleled that of myelinated nerve fiber density. Abnormal values for the two indices described above were found and two out of four cases demonstrated bimodality in the diameter histogram of UMNFs. Unlike MSA, ALS and PD have not been included in the disorders with cutaneous UMNF involvement. Our results supply the first evidence of morphological changes in cutaneous UMNFs in PD cases. In ordinary ALS cases, the emergence of such morphological changes is suggested in cases with long survival.

Expression of HLA-DR in peripheral nerve of amyotrophic lateral sclerosis.

To investigate the possibility of local antigen presentation within the peripheral nerve in amyotrophic lateral sclerosis (ALS), cryostat sections of 83 peripheral nerve biopsies were stained for the demonstration of HLA-DR using a monoclonal antibody. Forty samples showed increased expression of HLA-DR in endoneurium. The phenotypic characteristics of the HLA-DR positive cells are chiefly Schwann cells, using S-100 protein as a marker. We did not detect any co-expression between HLA-DR and NF (axons) and HLA-DR and myelin marker. We also detected co-expression between HLA-DR and NGFr in a majority of HLA-DR positive cells. Inflammatory cells were infrequent, being detected only in 11 cases, predominantly around epineurial blood vessels. Motor and sensory nerve biopsies performed simultaneously showed higher expression of HLA-DR in motor nerves in 2 out of 4 patients. The significance of these findings is not clear. The presence of endoneurial cells expressing HLA-DR suggests that an autoimmune mechanism may be involved in ALS having Schwann as the main target.

Nerve growth factor receptor immunostaining in the spinal cord and peripheral nerves in amyotrophic lateral sclerosis

In animal experiments, nerve transection is followed by expression of nerve growth factor receptors (NGFR) on Schwann cells of both motor and sensory nerve fibres distally to the site of the lesion. To determine whether denervated Schwann cells in amyotrophic lateral sclerosis (ALS) similarly express NGFR, a study was made of post-mortem material of peripheral nerves and ventral roots from ALS cases and age-matched controls, using immunolabelling methods. Dorsal roots and spinal cords were also examined for the presence of NGFR. In all the ALS cases and controls, NGFR immunostaining was seen in the outer layer of vessel walls, perineurial sheaths, connective tissue surrounding fascicles in nerve roots and in the substantia gelatinosa of the spinal cord. In ALS, NGFR staining was also present in the Schwann cells of degenerated nerve fibres in mixed peripheral nerves, in ventral roots and, to a lesser extent, in dorsal roots. NGFR immunoreactivity was also seen in elongated cells extending from the perifascicular connective tissue into the nerve fascicles. It is concluded that denervated Schwann cells in ALS express NGFR and that NGFR immunostaining on Schwann cells may be used as an indicator of axonal degeneration. The NGFR labelling in the dorsal roots supports the notion that ALS is not a pure motor syndrome.

Morphometry of intramuscular nerves in amyotrophic lateral sclerosis.

Morphometric analysis of 90 intramuscular nerves from the biopsied biceps muscles of 16 cases of amyotrophic lateral sclerosis (ALS) were done and compared with controls. In all fascicles (large and small) of ALS, the total number and the numbers of large and small myelinated fibers were significantly reduced to 52, 16, and 64% of controls, respectively. A histogram of the largest fascicles revealed a unimodal distribution and a shift to the left, showing a single peak at 1 micron diameter. The results indicate proximal and distal involvement of the most remote portions of the nerves to the muscle in ALS and support previous suggestions of a neuronopathy.

Morphometry of the degenerative process in the hypoglossal nerves in amyotrophic lateral sclerosis.

The peripheral hypoglossal nerves in 13 cases of amyotrophic lateral sclerosis (ALS) and five control cases were examined using morphometrical methods to demonstrate the degenerative process of motor nerve degeneration. The total number of myelinated fibers and their histograms were analyzed according to the degree of severity of the degeneration. Reduction of the total number of myelinated fibers in ALS hypoglossal nerves were graded in three groups: mild 65%-75%, moderate 50%-65% and severe 30%-50% of the myelinated fibers in controls. Each histogram of the remaining myelinated fibers showed different patterns corresponding to the degree of the degeneration and disclosed that the progressive reduction of large myelinated fibers was the fundamental change. Small myelinated fibers were not reduced, but increased, especially in the group with a moderate grade of degeneration. In plastic section, there were clusters of regenerated myelinated fibers. The transient increase of small myelinated fibers may be a reflexion of myelinated fiber regeneration during the progressive degenerative process of the motor neurons. The correlation between the degree of severity of the hypoglossal nerve degeneration and the atrophy of the tongue muscle and the duration of bulbar symptoms was examined and discussed.

Morphometric and biochemical studies of peripheral nerves in amyotrophic lateral sclerosis.

Phrenic nerves of 11 patients with amyotrophic lateral sclerosis studied postmortem contained only 33% of the normal number of large myelinated fibers (9 controls; p less than 0.001). In the phrenic nerves of these patients, there were 18% fewer large myelinated fibers in the distal segment than in the proximal segment (p less than 0.025). The ratio of axonal circumference to myelin lamellae in large myelinated fibers in the distal segment was 34% greater than that in control fibers (p less than 0.002). The proportion of acute axonal degeneration was the same at all levels (48.0 +/- 13.7%). Sural nerves of 21 patients with amyotrophic lateral sclerosis had more acute axonal degeneration and 30% fewer myelinated fibers (p less than 0.05) than controls; evidence of degeneration also extended to unmyelinated fibers. The amount of axonal transport of acetylcholinesterase in 9 sural nerves determined in vitro was reduced by 24% (p less than 0.05) and the apparent transport rate was reduced by 44% (p less than 0.01) compared with 4 controls. These findings show that in amyotrophic lateral sclerosis a small degree of dying-back change and of distal axonal atrophy is superimposed on the degeneration of motor neuron cell bodies, and that the disease effects spread beyond the motor neurons.

The ultrastructure of intramuscular nerves in amyotrophic lateral sclerosis.

Muscle biopsies of 11 patients suffering from amyotrophic lateral sclerosis (ALS) were examined and the i.m. nerves found in seven of them were examined by electron microscopy. In atrophied muscles there was a marked decrease of myelinated fibers. The ultrastructure of the remaining myelinated axons showed changes in the neurofilaments, mitochondria, and vesicles. There was a decrease in the number of unmyelinated fibers as well as the myelinated fibers. Occasionally, there was an increase of unmyelinated fibers containing small fine axons. There were corpora amylacea in unmyelinated axons and banded structures in the extracellular area of the Schwann cells of the unmyelinated fibers. Some of these findings were considered as the ultrastructural features of degeneration and regeneration in i.m. nerves of motoneurons in ALS.