Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing. METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region. RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes. CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Diving deep: zebrafish models in motor neuron degeneration research.

In the dynamic landscape of biomedical science, the pursuit of effective treatments for motor neuron disorders like hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) remains a key priority. Central to this endeavor is the development of robust animal models, with the zebrafish emerging as a prime candidate. Exhibiting embryonic transparency, a swift life cycle, and significant genetic and neuroanatomical congruencies with humans, zebrafish offer substantial potential for research. Despite the difference in locomotion-zebrafish undulate while humans use limbs, the zebrafish presents relevant phenotypic parallels to human motor control disorders, providing valuable insights into neurodegenerative diseases. This review explores the zebrafish's inherent traits and how they facilitate profound insights into the complex behavioral and cellular phenotypes associated with these disorders. Furthermore, we examine recent advancements in high-throughput drug screening using the zebrafish model, a promising avenue for identifying therapeutically potent compounds.

Predictive value of interleukin-6 combined with serum neuron-specific enolase on the prognosis of acute ischemic stroke.

OBJECTIVE: To explore the prognostic value of interleukin-6 (IL-6) combined with serum neuron specific enolase (NSE) in arterial atherosclerotic ischemic stroke. METHODS: 116 patients with arterial atherosclerotic ischemic stroke admitted to the emergency ward of our Hospital were retrospectively analyzed. According to the score of modified Rankin scale (mRS) at 90 days after discharge, the patients were divided into the poor prognosis group (mRS > 2, n = 32) and the good prognosis group (mRS ≤ 2, n = 84). Activities of Daily Living (ADL) was used to evaluate the level of independence in activities of daily living after treatment. RESULTS: The NIHSS score (14.91 ± 5.20 vs. 9.43 ± 4.30, P < 0.001), IL-6 (11.30 ± 3.11 vs. 6.75±1.28, P < 0.001) and NSE levels (12.47 ± 4.69 vs. 6.42 ± 1.32, P<0.001) in poor prognosis group were higher than those in the good prognosis group. At 90 days post-discharge, 100 % of the good prognosis group had ADL scores over 60, while in the poor prognosis group, 46.88 % scored 40-60, 40.63 % scored 20-40, 9.38 % scored under 20, and 3.13 % died. The AUC of NSE was 0.906 (95 % CI: 0.847-0.965, P < 0.001), the best cut-off value was 7.445 ng/mL, and the sensitivity and specificity were 75.0 % and 82.1 %, respectively. The AUC for IL-6 combined with NSE increased to 0.965 (95 %CI: 0.934-0.997, P < 0.001), and the sensitivity and specificity increased to 80.2 % and 92.9 %, respectively. CONCLUSION: IL-6 ≥ 6.805 pg/mL and NSE ≥ 7.445 ng/mL were independently associated with poor prognosis in patients with AIS, and the combined testing of the two indicators had a higher predictive value. These results suggested that the combined assay of IL-6 and NSE could be a novel marker for predicting poor prognosis in AIS.

Inhibiting sphingosine 1-phosphate lyase: From efficacy to mechanism.

Sphingosine-1 phosphate (S1P) is a lipid metabolite regulating diverse biological processes, including proliferation, differentiation, migration, and apoptosis, highlighting its physiological and therapeutic significance. Current S1P-based therapeutic approaches primarily focus on modulating the downstream signalling via targeting S1P receptors, however, this is challenged by incomplete receptor internalisation. Sphingosine-1-phosphate lyase (SPL) is a highly conserved enzyme that "gatekeeps" the final step of S1P degradation. Cognisant of the complex ligand and receptor interaction and dynamic metabolic networks, the selective modulation of SPL activity presents a new opportunity to regulate S1P biosynthesis and reveal its role in various systems. Over the past decade, an evolving effort has been made to identify new molecules that could block SPL activity in vitro or in vivo. This review focuses on summarising the current understanding of the reported SPL inhibitors identified through various screening approaches, discussing their efficacy in diverse model systems and the possible mechanism of action. Whilst effective modulation of S1P levels via inhibiting SPL is feasible, the specificity of those inhibitors remains inconclusive, presenting a clear challenge for future implications. Yet, none of the currently available SPL inhibitors is proven effective in elevating S1P levels within the central nervous system. This review article embraces future research focusing on investigating selective SPL inhibitors with high potency and possibly blood-brain-barrier permeability, which would aid the development of new S1P-based therapeutics for neurological disorders.

F wave analysis based on the compound muscle action potential scan.

INTRODUCTION/AIMS: Conventional F wave analysis involves a relatively uniform physiological environment induced by supramaximal stimulations. The F wave characteristics in a dynamic physiological condition, however, are rarely investigated. This study aimed to improve understanding of F wave properties in the more dynamic process by introducing a novel method to analyze F waves based on the compound muscle action potential (CMAP) scan technique. METHODS: Twenty four healthy subjects participated in the study. The CMAP scan was applied to record muscle responses in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles, respectively. F wave characteristics including mean F wave amplitude and latency (F-M latency), persistence and activating threshold were quantified. RESULTS: An average of 200 F waves per muscle were obtained from the CMAP scan recording. Weak to moderate correlations between F wave amplitude and stimulating intensity were observed in most of the APB (19 muscles; r = 0.33 ± 0.14, all p < .05) and ADM (23 muscles, r = 0.46 ± 0.16, all p < .05) muscles. Significantly longer mean F latency and lower activating F-threshold were found in the ADM muscles (F-M latency: APB: 25.43 ± 2.39 ms, ADM: 26.15 ± 2.32 ms, p < .05; F-threshold: APB: 7.68 ± 8.96% CMAP, ADM: 2.35 ± 2.42% CMAP, p < .05). DISCUSSION: This study introduces new features of F waves using the CMAP scan technique and identifies differences of F wave characteristics between the hand muscles. The CMAP scan based F waves analysis can be combined with the motor unit number estimation to assess functional alterations in motor neurons in neurological disorders.

Patients' and caregivers' perception of multidimensional and palliative care in amyotrophic lateral sclerosis - protocol of a German multicentre study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. METHODS: This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients' needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. PERSPECTIVE: It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. TRIAL REGISTRATION: The study is registered at ClinicalTrails.gov; NCT06418646.

A wave delay neural network for solving label-constrained shortest route query on time-varying communication networks.

The focus of the research is on the label-constrained time-varying shortest route query problem on time-varying communication networks. To the best of our knowledge, research on this issue is still relatively limited, and similar studies have the drawbacks of low solution accuracy and slow computational speed. In this study, a wave delay neural network (WDNN) framework and corresponding algorithms is proposed to effectively solve the label-constrained time-varying shortest routing query problem. This framework accurately simulates the time-varying characteristics of the network without any training requirements. WDNN adopts a new type of wave neuron, which is independently designed and all neurons are parallelly computed on WDNN. This algorithm determines the shortest route based on the waves received by the destination neuron (node). Furthermore, the time complexity and correctness of the proposed algorithm were analyzed in detail in this study, and the performance of the algorithm was analyzed in depth by comparing it with existing algorithms on randomly generated and real networks. The research results indicate that the proposed algorithm outperforms current existing algorithms in terms of response speed and computational accuracy.

Descriptive study of perineuronal net in enteric nervous system of humans and mice.

Perineuronal nets (PNN) are highly specialized structures of the extracellular matrix around specific groups of neurons in the central nervous system (CNS). They play functions related to optimizing physiological processes and protection neurons against harmful stimuli. Traditionally, their existence was only described in the CNS. However, there was no description of the presence and composition of PNN in the enteric nervous system (ENS) until now. Thus, our aim was to demonstrate the presence and characterize the components of the PNN in the enteric nervous system. Samples of intestinal tissue from mice and humans were analyzed by RT-PCR and immunofluorescence assays. We used a marker (Wisteria floribunda agglutinin) considered as standard for detecting the presence of PNN in the CNS and antibodies for labeling members of the four main PNN-related protein families in the CNS. Our results demonstrated the presence of components of PNN in the ENS of both species; however its molecular composition is species-specific.

Lavandula angustifolia Mill. inhibits high glucose and nicotine-induced Ca2+ influx in microglia and neuron-like cells via two distinct mechanisms.

Smoking remains a significant health problem in patients with type 2 diabetes mellitus. This study compared intracellular Ca2+ ([Ca2+]i) in microglia, neurons, and astrocytes in the presence of high glucose (HG) and nicotine and evaluated the effects of Lavandula angustifolia Mill. essential oil (LEO) on this process. [Ca2+]i concentrations were measured by monitoring the fluorescence of Fura-2 acetoxymethyl ester. Treatment with HG and nicotine significantly increased [Ca2+]i in both microglia and neurons through Ca2+ influx from extracellular sources. This increased Ca2+ influx in microglia, however, was significantly reduced by LEO, an effect partially inhibited by the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms.

Adolescents' challenging and grief-filled transitions when living with a parent with ALS: A qualitative interpretive study.

OBJECTIVE: The study aimed to explore the meaning for adolescents of living with a parent with amyotrophic lateral sclerosis (ALS). METHODS: The design is qualitative. Interviews were conducted between December 2020 and April 2022 with 11 adolescents (8-25 y), living in households with a parent with ALS in Sweden. The analysis was phenomenologically hermeneutical. RESULTS: The adolescents were in a difficult and exposed situation, especially if the parent had a severe disability and assistant care providers were in the home. Witnessing the gradual loss of the parent in an indefinite battle against time, while still needing them, elicited grief-filled and hard-to-manage emotions. Everyday life was turned upside down, resulting in greater responsibility for the adolescents, not only in helping with household chores and assisting the ill parent, but also in emotionally protecting both parents. It forced the adolescents to mature faster and put their own life on hold, triggering experiences of being limited. This, together with changing family roles yet being more attached to home, reinforced the imbalance in the adolescents' lives. The interpreted whole of the adolescents' narratives revealed that living with a parent with ALS meant a challenging and grieving transition during an already transition-filled adolescence, which left the adolescents struggling to keep a foothold on a life torn apart. CONCLUSION: The unbalanced life situation may hinder the adolescents' identity formation and emancipation, which are developmentally important for managing a healthy and independent adulthood. The results emphasize the importance of early targeted support to reach this vulnerable group in order to secure their health.

The Role of Alpha-Synuclein in Synucleinopathy: Impact on Lipid Regulation at Mitochondria-ER Membranes.

The protein alpha-synuclein (αSyn) plays a critical role in the pathogenesis of synucleinopathy, which includes Parkinson's disease and multiple system atrophy, and mounting evidence suggests that lipid dyshomeostasis is a critical phenotype in these neurodegenerative conditions. Previously, we identified that αSyn localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs), temporary functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we have analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinson's disease and controls, as well as three less affected brain regions of Parkinson's donors. To further assess synucleinopathy-related lipidome alterations, similar analyses were performed on the striatum of multiple system atrophy cases. Our data show region-and disease-specific changes in the levels of lipid species. Specifically, our data revealed alterations in the levels of specific phosphatidylserine species in brain areas most affected in Parkinson's disease. Some of these alterations, albeit to a lesser degree, are also observed multiples system atrophy. Using induced pluripotent stem cell-derived neurons, we show that αSyn contributes to regulating phosphatidylserine metabolism at MAM domains, and that αSyn dosage parallels the perturbation in phosphatidylserine levels. Our results support the notion that αSyn pathophysiology is linked to the dysregulation of lipid homeostasis, which may contribute to the vulnerability of specific brain regions in synucleinopathy. These findings have significant therapeutic implications.

SNMP1 is critical for sensitive detection of the desert locust aromatic courtship inhibition pheromone phenylacetonitrile.

BACKGROUND: Accurate detection of pheromones is crucial for chemical communication and reproduction in insects. In holometabolous flies and moths, the sensory neuron membrane protein 1 (SNMP1) is essential for detecting long-chain aliphatic pheromones by olfactory neurons. However, its function in hemimetabolous insects and its role for detecting pheromones of a different chemical nature remain elusive. Therefore, we investigated the relevance of SNMP1 for pheromone detection in a hemimetabolous insect pest of considerable economic importance, the desert locust Schistocerca gregaria, which moreover employs the aromatic pheromone phenylacetonitrile (PAN) to govern reproductive behaviors. RESULTS: Employing CRISPR/Cas-mediated gene editing, a mutant locust line lacking functional SNMP1 was established. In electroantennography experiments and single sensillum recordings, we found significantly decreased electrical responses to PAN in SNMP1-deficient (SNMP1-/-) locusts. Moreover, calcium imaging in the antennal lobe of the brain revealed a substantially reduced activation of projection neurons in SNMP1-/- individuals upon exposure to PAN, indicating that the diminished antennal responsiveness to PAN in mutants affects pheromone-evoked neuronal activity in the brain. Furthermore, in behavioral experiments, PAN-induced effects on pairing and mate choice were altered in SNMP1-/- locusts. CONCLUSIONS: Our findings emphasize the importance of SNMP1 for chemical communication in a hemimetabolous insect pest. Moreover, they show that SNMP1 plays a crucial role in pheromone detection that goes beyond long-chain aliphatic substances and includes aromatic compounds controlling reproductive behaviors.

Extracellular Vesicles as Mediators of Neuroinflammation in Intercellular and Inter-Organ Crosstalk.

Neuroinflammation, crucial in neurological disorders like Alzheimer's disease, multiple sclerosis, and hepatic encephalopathy, involves complex immune responses. Extracellular vesicles (EVs) play a pivotal role in intercellular and inter-organ communication, influencing disease progression. EVs serve as key mediators in the immune system, containing molecules capable of activating molecular pathways that exacerbate neuroinflammatory processes in neurological disorders. However, EVs from mesenchymal stem cells show promise in reducing neuroinflammation and cognitive deficits. EVs can cross CNS barriers, and peripheral immune signals can influence brain function via EV-mediated communication, impacting barrier function and neuroinflammatory responses. Understanding EV interactions within the brain and other organs could unveil novel therapeutic targets for neurological disorders.

Exercise training induces mild skeletal muscle adaptations without altering disease progression in a TDP-43 mouse model.

Exercise training is considered a non-pharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with Amyotrophic Lateral Sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete four weeks of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimes need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS.

PXL01 alters macrophage response with no effect on axonal outgrowth or Schwann cell response after nerve repair in rats.

Background: Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after repair of the sciatic nerve in healthy Wistar rats. Materials & methods: PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. Results: Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. Conclusion: PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages.

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Targeting neuronal epigenomes for brain rejuvenation.

Aging is associated with a progressive decline of brain function, and the underlying causes and possible interventions to prevent this cognitive decline have been the focus of intense investigation. The maintenance of neuronal function over the lifespan requires proper epigenetic regulation, and accumulating evidence suggests that the deterioration of the neuronal epigenetic landscape contributes to brain dysfunction during aging. Epigenetic aging of neurons may, however, be malleable. Recent reports have shown age-related epigenetic changes in neurons to be reversible and targetable by rejuvenation strategies that can restore brain function during aging. This review discusses the current evidence that identifies neuronal epigenetic aging as a driver of cognitive decline and a promising target of brain rejuvenation strategies, and it highlights potential approaches for the specific manipulation of the aging neuronal epigenome to restore a youthful epigenetic state in the brain.

Modern advances in spinal cord regeneration: hydrogel combined with neural stem cells.

Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

iPSC-Derived Astrocytes and Neurons Replicate Brain Gene Expression, Epigenetic, Cell Morphology and Connectivity Alterations Found in Autism.

Excessive inflammatory reactions and oxidative stress are well-recognized molecular findings in autism and these processes can affect or be affected by the epigenetic landscape. Nonetheless, adequate therapeutics are unavailable, as patient-specific brain molecular markers for individualized therapies remain challenging. METHODS: We used iPSC-derived neurons and astrocytes of patients with autism vs. controls (5/group) to examine whether they replicate the postmortem brain expression/epigenetic alterations of autism. Additionally, DNA methylation of 10 postmortem brain samples (5/group) was analyzed for genes affected in PSC-derived cells. RESULTS: We found hyperexpression of TGFB1, TGFB2, IL6 and IFI16 and decreased expression of HAP1, SIRT1, NURR1, RELN, GPX1, EN2, SLC1A2 and SLC1A3 in the astrocytes of patients with autism, along with DNA hypomethylation of TGFB2, IL6, TNFA and EN2 gene promoters and a decrease in HAP1 promoter 5-hydroxymethylation in the astrocytes of patients with autism. In neurons, HAP1 and IL6 expression trended alike. While HAP1 promoter was hypermethylated in neurons, IFI16 and SLC1A3 promoters were hypomethylated and TGFB2 exhibited increased promoter 5-hydroxymethlation. We also found a reduction in neuronal arborization, spine size, growth rate, and migration, but increased astrocyte size and a reduced growth rate in autism. In postmortem brain samples, we found DNA hypomethylation of TGFB2 and IFI16 promoter regions, but DNA hypermethylation of HAP1 and SLC1A2 promoters in autism. CONCLUSION: Autism-associated expression/epigenetic alterations in iPSC-derived cells replicated those reported in the literature, making them appropriate surrogates to study disease pathogenesis or patient-specific therapeutics.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.

INTRODUCTION: This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR). MATERIALS AND METHODS: The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR. RESULTS: SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. CONCLUSION: ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.