Amyotrophic Lateral Sclerosis Group Research Articles

Computed tomography-based radiological gynecomastia in SBMA as an independent differential diagnostic biomarker: a retrospective study.

Spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders that demonstrate overlapping clinical features, especially in the early stage. Therefore, the aim of this study was to investigate the utility of chest tomography (CT) imaging in distinguishing between SBMA and ALS. This was a retrospective study reviewing CT images from patients with SBMA and sporadic ALS and those in the control group. The CT images were assessed to measure the diameter and morphology of glandular tissue associated with gynecomastia. We compared CT-measured gynecomastia between the SBMA, ALS, and control groups. Additionally, correlation analyses were performed between the quantitative measurements of gynecomastia obtained from CT scans and various clinical/laboratory parameter in the SBMA group. 15 chest CT images were collected from SBMA, 41 from ALS, and 29 from control group. No statistical differences were observed in BMI, functional scales, or age at the time of CT scans between the SBMA and ALS groups. Despite similar functional scales and age in both groups, the mean glandular tissue diameter of breast tissue observed in chest CT imaging differed significantly between SBMA, ALS, and controls: 32.22 ± 12.57mm, 15.91 ± 4.81mm, and 15.76 ± 7.26mm, respectively. This disparity allowed for the differentiation of SBMA from ALS and controls with statistical significance. Clinical gynecomastia was 80%, while radiological gynecomastia was 93.3% in SBMA. A significantly higher prevalence of diffuse glandular morphology pattern in SBMA (50%) was observed, contrasting with the predominance of nodular morphology in ALS and controls (9.1% and 20%). Correlative analysis between glandular tissue diameter and other clinical/laboratory parameters within the SBMA group showed no specific finding. CT-based radiological gynecomastia effectively differentiated SBMA from ALS. These findings support the usefulness of radiological gynecomastia as a potential differential diagnostic marker for SBMA, especially in the early stages.

Evaluation of Split Hand Syndrome in Early Diagnosis of Amyotrophic Lateral Sclerosis by Nerve Conduction Study as a Diagnostic Tool

Background: Amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons that can present diversly. Needle electromyography (EMG) is the gold standard investigation for the diagnosis of ALS. Split hand syndrome (SHS) demonstrated by nerve conduction study (NCS); a noninvasive tool could be useful in diagnosing ALS. This study aimed to assess SHS by NCS in ALS. Methods: This diagnostic accuracy case-control study included 37 cases of ALS and 37 age and gender-matched controls. Compound muscle action potential (CMAP) and distal motor latency (DML) of median and ulnar nerves and the ratio of median and ulnar CMAP and DML were compared between study groups. The diagnostic validity testing of electrophysiological SHS was also done. Results: The mean age of the ALS and control groups were similar, 39.8±2.7 and 39.3±2.6 years, respectively. Sixteen (43.2%) ALS patients were in 30-59 years age group. Male-female ratio was 5.2. In the ALS group, median-ulnar CMAP ratio was lower and median-ulnar DML ratio was prolonged than the control. The diagnostic efficacy of median-ulnar CMAP ratio and DML ratio were calculated. A median-ulnar CMAP ratio cut-off value ≤1 showed 70% sensitivity, 97% specificity, 96% positive predictive value and 77% negative predictive value. A median-ulnar DML ratio cut-off value ≥1.5 showed 48% sensitivity, 89% specificity, 82% positive predictive value and 65% negative predictive value. Conclusion: NCS demonstrating SHS can be an important tool in the early diagnosis of ALS. J Bangladesh Coll Phys Surg 2024; 42: 350-354

Phrenic Nerve Sonography Alterations in Patients with ALS: Insight with Clinical and Neurophysiological Findings.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, and although the diagnosis is primarily based on clinical criteria, ENMG, as the "gold standard", does not always show detectable changes. Therefore, our study suggests that alterations in echogenicity and heterogeneity of the phrenic nerve (PN) may serve as potential additional diagnostic tools for ALS. Methods: Our study included 32 patients in the ALS group and 64 individuals in the control group. Each participant underwent an interview and completed questionnaires to collect clinical and demographic data, including age, gender, height, body mass index (BMI), hip and waist circumference, duration of illness, ALS-FRS-R score, comorbidities, and medication use. Ultrasound examinations of the PN were performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine equipped with a linear 4-18 MHz transducer. The ALS group participants underwent PN sonography and conduction examinations, arterial blood gas (ABG) analysis, respiratory function tests (RFT), and electroneuromyography (ENMG). Results: The study demonstrated that the phrenic nerve is significantly smaller on both sides in patients with ALS compared to the control group (p < 0.01). Changes in the homogeneity and echogenicity of the PN were also observed on both sides. On the right side, 43.8% of the nerves showed heterogeneity, 40.6% were isoechoic, and 21.9% were hyperechoic. On the left side, 59.4% of the nerves exhibited heterogeneity, 34.4% were isoechoic, and 28.1% were hyperechoic. Moreover, sonography on both sides showed significant correlation with ALS-FRS-R, COMPASS-31, and ENMG results. Conclusions: Our study highlights the importance of phrenic nerve ultrasound as a promising supplementary diagnostic tool for ALS. The significant differences in phrenic nerve size, echogenicity, and homogeneity between patients with ALS and the control group demonstrate that ultrasound imaging can detect morphological changes in the phrenic nerve. Incorporating phrenic nerve ultrasound into routine diagnostic protocols could improve early detection, enhance disease monitoring, and offer a more comprehensive understanding of the neurodegenerative processes in ALS.

Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\ heta\\:$$\\end{document}-band spectral power over time in the temporal region along with increased \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:{\\gamma\\:}_{l}$$\\end{document}-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread β-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS.

Clinical and Sociodemographic Factors Related to Amyotrophic Lateral Sclerosis in Spain: A Pilot Study

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknow etiology. Male sex is a well stablished risk factor, but other factors such as early and adult life expositions show contradictory evidence. Aim: to explore the link of clinical, sociodemographic, and occupational factors with ALS patients in Spain and the impact of these factors in functionality. Methods: A cross-sectional study was conducted with ALS patients and healthy controls. Registered variables were smoking, arterial hypertension, diabetes mellitus type 2, previous cancer to reproductive organs or breast, occupational exposure, and early life exposures. Functionality in ALS patients was compared according to each exposure. Results: The ALS group consisted of 59 participants and the control group of 90 participants. ALS patients showed a significant association with previous cancer (p = 0.011), occupational exposure (p &lt; 0.001), and older siblings (p = 0.029). ALS patients presented significant differences in BMI according to hypertension and older-sibling factors. Moreover, respiratory function was affected in patients with previous cancer (p = 0.031). Conclusions: Occupational exposure and previous cancer to reproductive organs or breast could be linked to ALS patients. In addition, hypertension and previous cancer could affect their BMI and respiratory function. Other factors such as longer smoking periods and exposition to older siblings could also characterize ALS patients.

Risk of depression in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea

Depression is frequently reported in amyotrophic lateral sclerosis (ALS) due to the disastrous prognosis of progressive motor impairment, but the risk of depression in ALS is still unclear. Therefore, we investigated the risk of depression in ALS and analyzed the effect of ALS-related physical disability on the risk of developing depression using the Korean National Health Insurance Service (KNHIS) database. A total of 2241 ALS patients, as defined by the International Classification Diseases (ICD, G12.21) and Rare Intractable Disease codes (V123), and 1:10 sex- and age-matched controls were selected from the KNHIS. After applying exclusion criteria (non-participation in national health screening, history of depression, or having missing data), 595 ALS patients and 9896 non-ALS individuals were finally selected. Primary outcome is newly diagnosed depression during follow-up duration defined by ICD code (F32 or F33). A Cox regression model was used to examine the hazard ratios (HRs) after adjustment for potential confounders. During the follow-up period, 283 cases of depression in the ALS group and 1547 in the controls were recorded. The adjusted HR for depression in ALS was 9.1 (95% confidence interval [CI] 7.87−10.60). The risk of depression was slightly higher in the disabled ALS group (aHR 10.1, 95% CI 7.98−12.67) than in the non-disabled ALS group (aHR 8.78, 95% CI 7.42−10.39). The relative risk of depression was higher in younger patients than in older patients, and in obese patients than in non-obese patients. Our study showed that ALS patients have an increased risk of depression compared to non-ALS individuals.

Cognitive reserve as a modulator of cognitive decline and of behavioral symptoms in patients with amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods: A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 (C9orf72) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results: For the ALS group, the statistical model explained 38.8% of variance in ECAS total (p < 0.001), 59.4% of executive functions (p < 0.001), and 55% of behavioral symptoms (p < 0.001). For controls, it accounted for 52.8% of variance in ECAS total (p < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups (p < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls (p = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom’ predictor in patients (p = 0.009). Conclusion: This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS.

Coupling motor evoked potentials and brain [18F]FDG-PET in Amyotrophic Lateral Sclerosis: preliminary findings on disease severity

BackgroundThe diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation. ObjectiveTo evaluate the ability of TMS-MEPs in delineating the neurophysiological UMN damage, and to determine the relationship between TMS-MEPs and [18F]FDG-PET measures of neural dysfunction. MethodsWe retrospectively selected 13 ALS patients who underwent, during the diagnostic process, the TMS-MEPs and [18F]FDG-PET scans. Demographic and clinical data were collected. For the MEP evaluation, we considered normal MEP, absent MEP, or significantly increased central-motor-conduction-time. For [18F]FDG-PET, we conducted voxel-wise analyses, both at single-subject and group levels, exploring hypometabolism and hypermetabolism patterns in comparison with a large dataset of healthy controls (HC). ResultsBased on TMS-MEPs, we identified 4/13 patients with normal MEP in all limbs (GROUP-NO), while 9/13 had an abnormal MEP in at least one limb (GROUP-AB). Despite the [18F]FDG-PET single-subject analysis revealed heterogenous expression of regional hypo- and hyper-metabolism patterns in the patients, the group-level analysis revealed a common hypometabolism, involving the precentral gyrus and the supplementary motor area, the paracentral lobule and the anterior cingulate cortex in the GROUP-AB. Moreover, exclusively for the GROUP-AB compared with HC, a relative hypermetabolism was observed in the right cerebellum, right inferior and middle temporal gyrus. The GROUP-NO showed no specific cluster of hypo- and hyper-metabolism compared to HC. ConclusionThis study showed altered brain metabolism only in the ALS group with abnormal MEPs, suggesting an association between the two biomarkers in defining the UMN damage.

Altered expression of human myxovirus resistance protein A in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. The etiology of sporadic ALS (sALS) has not yet been clarified. An increasing body of evidence suggests the involvement of viral infections and interferons (IFNs). Human myxovirus resistance protein A (MxA) is an IFN-induced dynamin-like GTPase that acts as a potent antiviral factor. This study examined MxA expression in ALS patient spinal cords using immunohistochemistry. Thirty-two cases of sALS (pathologically proven ALS-TDP), 10 non-ALS, other neurological disease control cases were examined. In most ALS cases, MxA cytoplasmic condensates were observed in the remaining spinal anterior horn neurons. The ALS group had a significantly higher rate of MxA-highly expressing neurons than the non-ALS group. Colocalization of MxA cytoplasmic condensate and transactive response DNA-binding protein 43 kDa (TDP-43)-positive inclusions was rarely observed. Because MxA has antiviral activity induced by IFNs, our results suggest that IFNs are involved in the pathogenesis of ALS in spinal cord anterior horn neurons. Our study also suggests that monitoring viral infections and IFN activation in patients with ALS may be critically important.

Association of serum Spp1 levels with disease progression in ALS and SBMA.

In comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1). This study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon-γ, interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and IL-17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels. In the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale-Revised (ALSFRS-R) scores (r = -0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57-72.53, p < 0.01). Neuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.

The effect of social support on the emotional well-being of people with amyotrophic lateral sclerosis: Exploring the mediating role of spirituality.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that, so far, is considered always fatal. Treatments mainly consist in increasing survival and aim to improve the quality of life of people with ALS (pwALS). Social support and spirituality have been shown to play a key role in pwALS' quality of life. Our study explored it in depth by investigating the underlying mechanisms linking social support, spirituality, and emotional well-being. Thirty-six pwALS underwent a battery of tests evaluating emotional well-being (emotional well-being scale of the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire), social support (6-item Social Support Questionnaire), and spiritual well-being (12-item Functional Assessment of Chronic Illness Therapy - Spiritual well-being). Our recruitment was web-based through the FILSLAN and the ARSLA websites as well as through Facebook® advertisements (ALS groups). Data were analyzed by Pearson correlation analysis and Process macro was used in an SPSS program to analyze the mediator variable effect. Availability of social support, spiritual well-being, and 2 of its dimensions, i.e., meaning and peace, were positively correlated with emotional well-being. The mediational analyses showed that spiritual well-being, meaning, and peace act as mediators in the association between availability of social support and good emotional well-being. Availability of social support and spirituality are essential for the emotional well-being of pwALS. Spirituality as a mediator between availability of social support and emotional well-being appears as real novel finding which could be explored further. Spiritual well-being, meaning, and peace appear as coping resources for pwALS. We provide practical guidance for professionals working with pwALS.

Choroid plexus enlargement in amyotrophic lateral sclerosis patients and its correlation with clinical disability and blood-CSF barrier permeability

BackgroundUsing in vivo neuroimaging techniques, growing evidence has demonstrated that the choroid plexus (CP) volume is enlarged in patients with several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. However, although animal and postmortem findings suggest that CP abnormalities are likely important pathological mechanisms underlying amyotrophic lateral sclerosis (ALS), the third most common neurodegenerative disease, no available study has been conducted to thoroughly assess CP abnormalities and their clinical relevance in vivo in ALS patients to date. Thus, we aimed to determine whether in vivo CP enlargement may occur in ALS patients. We also aimed to identify the relationships of CP volume with clinical disabilities and blood-CSF barrier (BCSFB) permeability in ALS patients.MethodsIn this retrospective study, based on structural MRI data, CP volume was assessed using a Gaussian mixture model and underwent further manual correction in 155 ALS patients and 105 age- and sex-matched HCs from October 2021 to April 2023. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to assess clinical disability. The CSF/serum albumin quotient (Qalb) was used to assess BCSFB permeability. Moreover, all the ALS patients completed genetic testing, and according to genetic testing, the ALS patients were further divided into genetic ALS subgroup and sporadic ALS subgroup.ResultsWe found that compared with HCs, ALS patients had a significantly higher CP volume (p < 0.001). Moreover, compared with HCs, CP volume was significantly increased in both ALS patients with and without known genetic mutations after family-wise error correction (p = 0.006 and p < 0.001, respectively), while there were no significant differences between the two ALS groups. Furthermore, the CP volume was significantly correlated with the ALSFRS-r score (r = -0.226; p = 0.005) and the Qalb (r = 0.479; p < 0.001) in ALS patients.ConclusionOur study first demonstrates CP enlargement in vivo in ALS patients, and continues to suggest an important pathogenetic role for CP abnormalities in ALS. Moreover, assessing CP volume is likely a noninvasive and easy-to-implement approach for screening BCSFB dysfunction in ALS patients.

Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy.

The discovery of hexanucleotide repeats expansion (RE) in Chromosome 9 Open Reading frame 72 (C9orf72) as the major genetic cause of amyotrophic lateral sclerosis (ALS) and the association between intermediate repeats in Ataxin-2 (ATXN2) with the disorder suggest that repetitive sequences in the human genome play a significant role in ALS pathophysiology. Investigating the frequency of repeat expansions in ALS in different populations and ethnic groups is therefore of great importance. Based on these premises, this study aimed to define the frequency of REs in the NIPA1, NOP56, and NOTCH2NLC genes and the possible associations between phenotypes and the size of REs in the Italian population. Using repeat-primed-PCR and PCR-fragment analyses, we screened 302 El-Escorial-diagnosed ALS patients and compared the RE distribution to 167 age-, gender-, and ethnicity-matched healthy controls. While the REs distribution was similar between the ALS and control groups, a moderate association was observed between longer RE lengths and clinical features such as age at onset, gender, site of onset, and family history. In conclusion, this is the first study to screen ALS patients from southern Italy for REs in NIPA1, NOP56, and NOTCH2NLC genes, contributing to our understanding of ALS genetics. Our results highlighted that the extremely rare pathogenic REs in these genes do not allow an association with the disease.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Analysis of Heart Rate Variability in Individuals Affected by Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) produces alterations in the autonomic nervous system (ANS), which explains the cardiac manifestations observed in patients. The assessment of heart rate variability (HRV) is what best reflects the activity of the ANS on heart rate. The Polar H7 Bluetooth® device proves to be a non-invasive and much faster technology than existing alternatives for this purpose. The goal of this study is to determine HRV using Polar H7 Bluetooth technology in ALS patients, comparing the obtained measurements with values from healthy individuals. The sample consisted of 124 participants: 68 diagnosed with ALS and 56 healthy individuals. Using Polar H7 Bluetooth technology and the ELITE HRV application, various HRV measurements were determined for all participants, specifically the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, LF, HF, LF/HF ratio, HR average, and HF peak frequency. Statistically significant differences were observed between ALS patients and healthy individuals in the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, HF, and LF, where healthy individuals exhibited higher scores. For the HR average, the ALS group showed a higher value. Values were similar when comparing men and women with ALS, with only a higher HF peak frequency observed in women. The Polar H7 Bluetooth® device is effective in determining heart rate variability alterations in ALS, being a promising prognostic tool for the disease.

Corneal nerves and amyotrophic lateral sclerosis: an in vivo corneal confocal imaging study.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27months. In vivo corneal confocal microscopy, assessing the sub-basal nerve plexus of the cornea, has been proposed as a potential biomarker for ALS. We aimed to determine whether the assessment of corneal nerves using in vivo confocal microscopy can serve as an imaging biomarker for ALS. A single-centre prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. The corneal sub-basal nerve plexus was analysed using in vivo confocal microscopy. An automated algorithm (ACCMetrics) was used to evaluate corneal parameters: nerve fibre density, nerve branch density, nerve fibre length, nerve fibre area, nerve total branch density, nerve fibre width, and nerve fractal dimension. Twenty-two patients with ALS and 30 controls were included. No significant differences were found between ALS and control groups for all corneal parameters (p > 0.05). Corneal sensitivity did not differ between groups, and no correlation was identified between corneal nerve parameters and ALS disease duration, severity and rate of progression (p > 0.05). The present study does not support the use of in vivo corneal confocal microscopy as an early diagnostic or prognostic tool for ALS. Further research, especially longitudinal investigations, is needed to understand any potential corneal innervation changes as ALS progresses.

Using an expanded algorithm to estimate prevalence of amyotrophic lateral sclerosis in U.S. and UK.

There is an increasing need to better understand the burden of amyotrophic lateral sclerosis (ALS) using real-world data (RWD). However, identifying ALS cases using RWD presents several challenges due to the rarity of ALS and the differences in database coding systems. MarketScan claims, and the UK Clinical Practice Research Datalink (CPRD) databases were searched for diagnosis codes of ALS or MND, the only drugs approved for treating ALS (riluzole and edaravone) and clinical visits with 12-month enrolment prior to 1 January 2011. The main algorithm required ≥ 1 ALS diagnosis code together with prescriptions or clinical visits. We expanded the existing algorithm to identify unspecific (possible) ALS group that had codes for motor neuron disease (MND) and the ALS drugs. The study period was from 1 January 2011 until 31 December 2020. We identified 16,246 patients with ≥ 1 ALS code in Marketscan (denominator n = 85,279,619), yet only 184 were found in the UK CPRD (denominator n = 21,318,589). Using the main algorithm 9,433 ALS patients were included in MarketScan, with a prevalence ranged between 4.5 per 100,000 in 2019 and 6.2 in 2015. In MarketScan, 3,658 (4.3 per 100,000) had ≥ 1 MND code and the ALS drug codes (possible cases). In CPRD, 47.9% of 2,785 patients with ≥ 1 MND code had a prescription for riluzole (6.3 per 100,000), regarded as possible ALS cases. The expanded algorithm enabled the identification of a large population with ALS, or possible ALS, and the estimation of ALS prevalence in MarketScan and CPRD.

Biochemical parameters as a tool to assess the nutritional status of patients with amyotrophic lateral sclerosis.

The research aimed to analyze blood biochemical parameters in patients with amyotrophic lateral sclerosis and to determine whether they can be used to assess their nutritional status. The study included 45 patients diagnosed with amyotrophic lateral sclerosis (ALS): 28 (62.2%) were men and 17 (37.8%) were women. The mean age of the study participants was 50.69 ± 7.24 years. The control group consisted of 30 practically healthy individuals. Compared with practically healthy individuals, patients with ALS had significantly lower blood parameters, including total lymphocyte count (1.49 ± 0.11 vs. 2.86 ± 0.25, p < 0.05), total protein (60.55 ± 2.38 vs. 77.80 ± 4.41, p < 0.05), albumin (33.70 ± 2.03 vs. 46.49 ± 3.22, p < 0.05), urea (3.09 ± 0.36 vs. 5.37 ± 0.50, p < 0.05), creatinine (51.28 ± 4.42 vs. 70.91 ± 5.13, p < 0.05), and transferrin (1.84 ± 0.12 vs. 2.32 ± 0.10, p < 0.05). These parameters correspond to first-degree malnutrition. There were direct correlations between anthropometric and biochemical parameters in the ALS group. BMI correlated with the blood levels of total protein (r = 0.22, p < 0.05), albumin (r = 0.27, p < 0.05), urea (r = 0.33, p < 0.05), creatinine (r = 0.30, p < 0.05), transferrin (r = 0.18, p < 0.05), and total lymphocyte count (r = 0.20, p < 0.05). PNI correlated with the blood levels of total protein (r = 0.53, p < 0.05), albumin (r = 0.87, p < 0.05), total cholesterol (r = 0.34, p < 0.05), transferrin (r = 0.40, p < 0.05), total lymphocyte count (r = 0.79, p < 0.05), urea (r = 0, 37, p < 0.05), and creatinine (r = 0.32, p < 0.05). The study presents compelling evidence supporting the utilization of biochemical parameters, including total protein, albumin, urea, creatinine, transferrin, and total lymphocyte count, for potentially evaluating the nutritional status of individuals diagnosed with ALS.

Plasma and salivary acetylcholinesterase activity in amyotrophic lateral sclerosis

Assessment of plasma and salivary acetylcholinesterase (AChE) activity in patients with amyotrophic lateral sclerosis (ALS) and in an animal model of the disease. We studied 41 participants, aged 31 to 71 years, including 17 patients with diagnosed ALS (ALS group, average age 62.3±2.2), 9 patients with ALS mimics (disease control, average age 58.1±2.9), and 15 healthy people (normal control, average age 57.7±2.3). Plasma and salivary AChE activity was measured by using the Ellman colorimetric method. ALS severity was assessed using the ALSFRS-R scale. The King's College staging system and the Milano-Torino Scale (MiToS) were used to determine the stage of the disease. Transgenic FUS-mice were used as ALS model. Plasma AChE activity in the ALS group did not significantly differ from the control groups. There was also no significant correlation between plasma AChE activity and disease parameters such as the stage, duration, rate of progression, and severity. In transgenic FUS-mice plasma AChE activity also did not differ from wild-type mice. However, it has been shown that patients with ALS have significantly higher saliva AChE activity compared to normal controls. However, patients with the bulbar form of ALS had significantly higher values of salivary AChE activity compared to healthy controls. In patients with the bulbar form of ALS, an increase in salivary AChE activity was noted, which can be used for diagnostic and prognostic purposes. There is no significant change in plasma AChE activity in ALS patients.

Assessment of Rab geranylgeranyltransferase subunit beta in amyotrophic lateral sclerosis.

Geranylgeranyltransferase Subunit Beta (RABGGTB) was expressed at higher levels in patients with Amyotrophic lateral sclerosis (ALS) compared with healthy controls. This study aims to observe the expression of RABGGTB in different cells from patients with ALS and different diseases. In this case-control study, we collected peripheral blood from patients with ALS and healthy controls, and compared the expression of RABGGTB in natural killer cells (NK), T cells and B cells between patients with ALS and healthy controls by flow cytometry. And compared the expression of RABGGTB in monocytes and monocyte-derived macrophages from patients with ALS, Parkinson's disease (PD), acute cerebrovascular disease (ACVD), and healthy controls by flow cytometry and immunofluorescence. Then flow cytometry was used to detect the expression of RABGGTB in monocytes from SOD1G93A mice and WT mice. The expression of RABGGTB was not significantly changed in NK cells, cytotoxic T cells (CTL), helper T cells (Th), regulatory T cells (Treg), and B cells from patients with ALS compared to healthy controls. And the expression of RABGGTB in monocytes and monocyte-derived macrophages was higher in the ALS group than in the PD, ACVD and control group. The expression of RABGGTB was significantly higher in monocytes of SOD1G93A mice compared to WT mice. These findings suggest that RABGGTB expression was increased in monocytes and monocyte-derived macrophages from patients with ALS, not in NK, CTL, Th, Treg, and B cells. Future studies are needed to find the clinical implication of RABGGTB in ALS.