Nervous System Control Research Articles

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling

Serotonergic neurons in the central nervous system control behavior and mood, but knowledge of the roles of serotonergic circuits in the regulation of immune homeostasis is limited. Here, we employ mouse genetics to investigate the functions of enteric serotonergic neurons in the control of immune responses and find that these circuits regulate IgA induction and boost host defense against oral, but not systemic Salmonella Typhimurium infection. Enteric serotonergic neurons promote gut-homing, retention and activation of intestinal plasmacytoid dendritic cells (pDC). Mechanistically, this neuro-immune crosstalk is achieved through a serotonin-5-HT receptor 7 (HTR7) signaling axis that ultimately facilitates the pDC-mediated differentiation of IgA+ B cells from IgD+ precursors in the gut. Single-cell RNA-seq data further reveal novel patterns of bidirectional communication between specific subsets of enteric neurons and lamina propria DC. Our findings thus reveal a close interplay between enteric serotonergic neurons and gut immune homeostasis that enhances mucosal defense.

Dynamical network-based evaluation for neuromuscular dysfunction in stroke-induced hemiplegia during standing

BackgroundA given movement requires precise coordination of multiple muscles under the control of center nervous system. However, detailed knowledge about the changing characteristics of neuromuscular control for multi-muscle coordination in post-stroke hemiplegic patients during standing is still lacking. This study aimed to investigate the hemiplegia-linked neuromuscular dysfunction during standing from the perspective of multi-muscle dynamical coordination by utilizing a novel network approach – weighted recurrence network (WRN).MethodsTen male hemiplegic patients with first-ever stroke and 10 age-matched healthy male adults were instructed to stand on a platform quietly for 30 s with eyes opened and eyes closed, respectively. The WRN was constructed based on the surface electromyography signals of 16 muscles from trunk, hips, thighs and calves. Relevant topological parameters, including clustering coefficient (C) and average shortest path length (L), were extracted to evaluate the dynamical coordination of multiple muscles. A measure of node centrality in network theory, degree of centrality (DC), was innovatively introduced to assess the contribution of single muscle in the multi-muscle dynamical coordination. The standing-related assessment metric, center of pressure (COP), was provided by the platform directly.ResultsResults showed that the post-stroke hemiplegic patients stood with remarkably higher similarity of muscle activation and more coupled intermuscular dynamics, characterized by higher C and lower L than the healthy subjects (p < 0.05). The DC values and rankings of back, hip and calf muscles on the affected side were significantly decreased, whereas those on the unaffected side were significantly increased in hemiplegia group compared with the healthy group (p < 0.05). Without visual feedback, subjects exhibited enhanced muscle coordination and increased muscle involvement (p < 0.05). A decrease in C and an increase in L of WRN were observed with decreased COP areas (p < 0.05).ConclusionsThese findings revealed that stroke-induced hemiplegia could significantly influence the neuromuscular control, which was manifested as more coupled intermuscular dynamics, abnormal deactivation of muscles on affected side and compensation of muscles on unaffected side from the perspective of multi-muscle coordination. Enhanced multi-muscle dynamical coordination was strongly associated with impaired postural control. This study provides a novel analytical tool for evaluation of neuromuscular dysfunction and specification of responsible muscles for impaired postural control in stroke-induced hemiplegic patients, and could be potentially applied in clinical practice.

Cellular mechanisms of synchronized rhythmic burst generation in the ventromedial hypothalamus.

The ventromedial hypothalamus (VMH) plays an important role in feeding behavior and control of the sympathetic nervous system (SNS). The VMH includes a group of neurons that exhibit strong synchronized rhythmic burst firing (so-called VMH oscillation). This VMH oscillation is glucose inhibited, responsive to feeding-related peptides, and is functionally coupled to outputs of the SNS. However, the details of its rhythm generation and synchronization mechanisms are unknown. In the present study, we investigated cellular mechanisms of VMH oscillation by means of electrophysiological recordings and calcium imaging in juvenile rat slice preparations including the VMH. In the electrophysiological study, we performed membrane potential recording from neurons in the vicinity of pipettes for field potential recording. We found that the rhythmic bursts in the VMH were preserved in low Ca2+/high Mg2+ synaptic transmission blockade solution. During membrane hyperpolarization by current injection, the action potential was largely inhibited, but fluctuation of the membrane potential remained with a frequency similar to that at resting potential level. The electric VMH oscillation disappeared after application of either a gap junction blocker, carbenoxolone (100µM), or a persistent sodium channel blocker, riluzole (20µM). Membrane potentials and input resistances of rhythmic burst neurons in the VMH were not significantly changed during these manipulations. A calcium imaging study revealed that all VMH cells exhibiting synchronized rhythmic activity detected by intracellular calcium increases were silenced following the application of carbenoxolone. These results suggest that VMH oscillation arises from the activation of persistent sodium channels and coupling via gap junctions.

Dopaminergic neuronal regulation determines innate immunity of Caenorhabditis elegans during Klebsiella aerogenes infection

The innate immune signals are the front line of host defense against bacterial pathogens. Pathogen-induced harmful effects, such as reduced neuronal signals to the intestine, affect the host's food sensing and dwelling behavior. Here, we report that dopamine and kpc-1 signals control the intestinal innate immune responses through the p38/PMK-1 MAPK signaling pathway in C. elegans. K. aerogenes infection in C. elegans affects the food-dwelling behavior, which depends on dopamine regulation. The absence of the dopamine receptor (dop-1) and transporter (dat-1) increases attraction to the pathogen instead of avoidance. The K. aerogenes infection affects age-1 regulation through the furin-like proprotein convertase (kpc-1); the absence of kpc-1 affects environment-dependent dauer formation. In contrast, the dop-1 mutation antagonistically regulates intestinal immune regulation, while the kpc-1 mutation partially regulates the p38/PMK-1 MAPK pathway. Our findings indicate that dopamine and kpc-1signaling from the nervous system control intestinal immunity in an antagonistic and agonistic manner, respectively.

Characterizing upper limb motor dysfunction with temporal and spatial distribution of muscle synergy extracted from high-density surface electromyography.

Objective.To promote the development of objective and comprehensive motion function assessment for patients, based on high-density surface electromyography (HD-sEMG), this study investigates the temporal and spatial variations of neuromuscular activities related to upper limb motor dysfunction.Approach.Patients with unilateral upper limb motor dysfunction and healthy controls were enrolled in the study. HD-sEMG was collected from both arms while they were performing eight hand and wrist movements. Muscle synergies were extracted from the HD-sEMG. Symmetry of bilateral upper limb synergies and synergy differences between motions were proposed as spatial indicators to measure alterations in synergy spatial distribution. Additionally, as a temporal characteristic, the correlation of bilateral upper limb activation coefficient was proposed to describe the coordination control of the central nervous system. All temporal and spatial indicators were compared between patients and healthy subjects.Main results.The patients showed a significant decrease (p< 0.05) in the symmetry of bilateral upper limb synergy spatial distribution and correlation of bilateral upper limb activation coefficient. Patients with motor dysfunction also showed an increase in synergy similarity between motions, indicating altered spatial distribution of muscle synergies.Significance.These findings provide valuable insights into specific patterns associated with motor dysfunction, informing motor function assessment, and guiding targeted interventions and rehabilitation strategies for neurologically disordered patients.

EndoFLIP evaluation of the pylorus during minimal invasive Ivor–Levis esophagectomy

Background/Aims During esophagectomy for malignancy, the anterior and posterior branches of the vagus nerve are transected in order to achieve surgical radicality. This leads to loss of central nervous system-control of the pylorus which may lead to delayed gastric emptying. We aimed to investigate the feasibility of the EndoFLIP technique for assessment of pyloric biomechanical properties in patients undergoing esophagectomy. Methods A feasibility study in six patients undergoing surgery was conducted. EndoFLIP measurements were carried out preoperative (Pre-op), after surgical resection (Post-op) and following prophylactic balloon dilatation of the pylorus (Post-dil). By measuring the cross-sectional area and pressure of the pylorus the pyloric compliance and the incremental pressure-strain elastic modulus (Ep) were calculated. Results Placing the catheter in the pyloric region was successfully achieved in all six patients. No complications were observed. Resection of the esophagus increased the incremental pyloric elastic modulus (Ep) from 0.59 ± 0.18 kPa to 0.99 ± 0.34 kPa (p = 0.03). After dilatation, the Ep was reduced to 0.53 ± 0.23 kPa (p = 0.04), which was close to Pre-op (p = 0.62). The pyloric compliance showed a similar pattern as that found for Ep. Conclusion The EndoFLIP system holds promise for assessment of biomechanics of the pyloric region in patients undergoing esophagectomy for cancer.

Neuro-intestinal acetylcholine signalling regulates the mitochondrial stress response in Caenorhabditis elegans

Neurons coordinate inter-tissue protein homeostasis to systemically manage cytotoxic stress. In response to neuronal mitochondrial stress, specific neuronal signals coordinate the systemic mitochondrial unfolded protein response (UPRmt) to promote organismal survival. Yet, whether chemical neurotransmitters are sufficient to control the UPRmt in physiological conditions is not well understood. Here, we show that gamma-aminobutyric acid (GABA) inhibits, and acetylcholine (ACh) promotes the UPRmt in the Caenorhabditis elegans intestine. GABA controls the UPRmt by regulating extra-synaptic ACh release through metabotropic GABAB receptors GBB-1/2. We find that elevated ACh levels in animals that are GABA-deficient or lack ACh-degradative enzymes induce the UPRmt through ACR-11, an intestinal nicotinic α7 receptor. This neuro-intestinal circuit is critical for non-autonomously regulating organismal survival of oxidative stress. These findings establish chemical neurotransmission as a crucial regulatory layer for nervous system control of systemic protein homeostasis and stress responses.

Electroceuticals and Magnetoceuticals in Gastroenterology.

In the realm of gastroenterology, the inadequacy of current medical treatments for gastrointestinal (GI) motility disorders and inflammatory bowel disease (IBD), coupled with their potential side effects, necessitates novel therapeutic approaches. Neuromodulation, targeting the nervous system's control of GI functions, emerges as a promising alternative. This review explores the promising effects of vagal nerve stimulation (VNS), magnetic neuromodulation, and acupuncture in managing these challenging conditions. VNS offers targeted modulation of GI motility and inflammation, presenting a potential solution for patients not fully relieved from traditional medications. Magnetic neuromodulation, through non-invasive means, aims to enhance neurophysiological processes, showing promise in improving GI function and reducing inflammation. Acupuncture and electroacupuncture, grounded in traditional medicine yet validated by modern science, exert comprehensive effects on GI physiology via neuro-immune-endocrine mechanisms, offering relief from motility and inflammatory symptoms. This review highlights the need for further research to refine these interventions, emphasizing their prospective role in advancing patient-specific management strategies for GI motility disorders and IBD, thus paving the way for a new therapeutic paradigm.

Analysis of oscillations of the center of pressure in postural control

Posture results from intricate interactions between the central nervous system's control mechanisms, sensory integration, and musculoskeletal responses, encompassing two levels: sustaining tonic muscle activity for posture and making adjustments to maintain balance in response to disturbances. Due to its complexity, assessing posture with simple methods is challenging, necessitating the use of advanced techniques like stabilometric platforms to measure postural stability through the center of pressure oscillations, akin to an inverted pendulum concept, offering a comprehensive understanding of postural control mechanisms. Materials and Methods: The study aims to analyze the trajectory of the center of pressure (COP) in relation to the gender of the subjects, through directional indices (DI) and oscillation ratio (OR), in the process of posture maintenance. The study included a sample of 50 young subjects (21-24 years), sports practitioners, divided into two equal groups. Results: The study findings indicate that gender does not influence COP DI. However, there's a significant disparity between anteroposterior (AP) DI values (0.70) and mediolateral (ML) DI values (0.54). The results suggest a predominant reliance on AP control mechanisms for maintaining balance, regardless of gender. When visual input is absent, there's a slight increase in AP DI (0.72) and a decrease in ML DI (0.52), indicating a shift in balance strategies. In terms of OR, significant differences are observed based on gender, oscillation direction, and visual input. Female subjects exhibit higher AP OR (6.5) compared to males (5.1). Under closed eyes conditions, both genders show decreased AP OR (6.0 for females, 4.7 for males), indicating a reliance on alternative balance strategies in the absence of visual cues. Conclusion: The study highlights the complexity of postural control and empha-sizes the influence of factors like gender and visual input on postural stability metrics, providing valuable insights for further research and clinical practice. The analysis reveals that around 60% of COP oscillations occur in the AP direction, regardless of visual input changes. This underscores the critical role of AP control in maintaining balance, suggesting targeted interventions to enhance stability should prioritize this aspect. Keywords: postural control, oscillations of the center of pressure, stabilometric platform.

Critical review on physiological aspects of Samana Vata

Background: Samana Vata which is located near the seat of Agni and it have role in digestion as well as in the assimilation of ingested food. Anna Grahana, Pachana, Vivechana and Munchan are the functions of Samana Vata. The physiological functions of Samana Vata can be correlated with enteric nervous system which is known as the second brain, and parasympathetic and sympathetic supply of autonomic nervous system. ENS functions by maintaining the enteric homeostasis and also act as modulator in gut barrier functions. After the food reaches stomach, several digestive juice acts on it. Gastric juice, pancreatic juice, all contains important digestive enzymes and act on food. Secretion of this enzyme is mostly under the control of intrinsic and extrinsic enteric nervous system. Aims and Objective: To critically analyse the concept of Samana Vata and find out the correlation with modern physiology. Materials and Methods: Literature review was referred from different classical text books and relevant modern textbooks, articles, data bases like google scholar, pubmed. Conclusion: Samana Vata chiefly locates in the middle part of body. It is primarily responsible for stimulation of Agni and leads to digestion, absorption, separation of essence and waste material. Function of Samana Vata, described by Acharyas can be compared with the physiological function of enteric nervous system. It can be partially correlated with enteric nervous system, sympathetic and parasympathetic supply of autonomic nervous system.

Lateral parabrachial nucleus astrocytes control food intake.

Food intake behavior is under the tight control of the central nervous system. Most studies to date focus on the contribution of neurons to this behavior. However, although previously overlooked, astrocytes have recently been implicated to play a key role in feeding control. Most of the recent literature has focused on astrocytic contribution in the hypothalamus or the dorsal vagal complex. The contribution of astrocytes located in the lateral parabrachial nucleus (lPBN) to feeding behavior control remains poorly understood. Thus, here, we first investigated whether activation of lPBN astrocytes affects feeding behavior in male and female rats using chemogenetic activation. Astrocytic activation in the lPBN led to profound anorexia in both sexes, under both ad-libitum feeding schedule and after a fasting challenge. Astrocytes have a key contribution to glutamate homeostasis and can themselves release glutamate. Moreover, lPBN glutamate signaling is a key contributor to potent anorexia, which can be induced by lPBN activation. Thus, here, we determined whether glutamate signaling is necessary for lPBN astrocyte activation-induced anorexia, and found that pharmacological N-methyl D-aspartate (NMDA) receptor blockade attenuated the food intake reduction resulting from lPBN astrocyte activation. Since astrocytes have been shown to contribute to feeding control by modulating the feeding effect of peripheral feeding signals, we further investigated whether lPBN astrocyte activation is capable of modulating the anorexic effect of the gut/brain hormone, glucagon like peptide -1, as well as the orexigenic effect of the stomach hormone - ghrelin, and found that the feeding effect of both signals is modulated by lPBN astrocytic activation. Lastly, we found that lPBN astrocyte activation-induced anorexia is affected by a diet-induced obesity challenge, in a sex-divergent manner. Collectively, current findings uncover a novel role for lPBN astrocytes in feeding behavior control.

The effect of a short breathing intervention on postural control and heart rate variability

AbstractPurposeThe objective of this study was to determine the immediate effect of a short breathing intervention on postural control and heart rate variability in healthy individuals.Materials/MethodsThe study involved 28 participants. Heart rate variability and heart rate were measured using a Polar (H10) sensor, and the sway path during posturography was recorded using the NeuroCom system, with participants standing on a firm then a foam surface in the eyes open and eyes closed conditions. All measurements were performed before and after the breathing intervention to provide baseline and post-intervention data. A short breathing intervention was performed between testing to stimulate the autonomic nervous system. In the Wilcoxon matched pairs comparison using Statistica software, P &lt; 0.05 was considered statistically significant.ResultsThe breathing intervention caused a significant decrease in heart rate variability and an increase in heart rate. In the eyes closed condition, on a firm surface, the breathing intervention significantly reduced the sway path.ConclusionsThe breathing intervention reduced the sway path in conditions without visual information but appeared to have no effect on balance in conditions with visual information, suggesting that the postural function of the diaphragm becomes more prominent in nonvisual conditions. We obtained evidence of the relationship between the autonomic nervous system and postural control. The stimulation of the sympathetic tone by means of the breathing intervention had a significant effect on postural control on firm and foam surfaces without visual information and decreased postural sway.

Remote optogenetic control of the enteric nervous system and brain-gut axis in freely-behaving mice enabled by a wireless, battery-free optoelectronic device

Wireless activation of the enteric nervous system (ENS) in freely moving animals with implantable optogenetic devices offers a unique and exciting opportunity to selectively control gastrointestinal (GI) transit in vivo, including the gut-brain axis. Programmed delivery of light to targeted locations in the GI-tract, however, poses many challenges not encountered within the central nervous system (CNS). We report here the development of a fully implantable, battery-free wireless device specifically designed for optogenetic control of the GI-tract, capable of generating sufficient light over large areas to robustly activate the ENS, potently inducing colonic motility ex vivo and increased propulsion in vivo. Use in in vivo studies reveals unique stimulation patterns that increase expulsion of colonic content, likely mediated in part by activation of an extrinsic brain-gut motor pathway, via pelvic nerves. This technology overcomes major limitations of conventional wireless optogenetic hardware designed for the CNS, providing targeted control of specific neurochemical classes of neurons in the ENS and brain-gut axis, for direct modulation of GI-transit and associated behaviours in freely moving animals.

Gamma knife radiosurgery following whole-brain radiation

In this study, we aimed to determine outcomes for patients requiring salvage stereotactic radiosurgery (SRS) who have progression of brain metastatic disease after initial treatment with whole-brain radiation (WBRT). This is a retrospective analysis of a prospective database of 112 patients who were treated with salvage SRS after experiencing failure following WBRT treatment with salvage SRS. Collectively, the patients had a median overall survival of 7 months after salvage SRS. Patients who had more than two brain metastases had a significantly shorter median survival but were not subjected to increased risk for distant brain failure. We also found that a short intervening time between WBRT and central nervous system (CNS) failure did not seem to worsen the nervous system control or reduce patient survival. Small cell lung cancer (SCLC) was associated with decreased overall survival and CNS control. In conclusion, SRS use following WBRT is safe and effective in the majority of patients. Patients with rapid failure after WBRT can be successfully salvaged with SRS. The findings also shed light on the overall poor outcomes, coupled with low median survival and high rates of CNS failure, in patients suffering multiple metastases stemming from SCLC.

Pathophysiology of Severe Burn Injuries: New Therapeutic Opportunities From a Systems Perspective.

Severe burn injury elicits a profound stress response with the potential for high morbidity and mortality. If polytrauma is present, patient outcomes appear to be worse. Sex-based comparisons indicate females have worse outcomes than males. There are few effective drug therapies to treat burn shock and secondary injury progression. The lack of effective drugs appears to arise from the current treat-as-you-go approach rather than a more integrated systems approach. In this review, we present a brief history of burns research and discuss its pathophysiology from a systems' perspective. The severe burn injury phenotype appears to develop from a rapid and relentless barrage of damage-associated molecular patterns, pathogen-associated molecular patterns, and neural afferent signals, which leads to a state of hyperinflammation, immune dysfunction, coagulopathy, hypermetabolism, and intense pain. We propose that if the central nervous system control of cardiovascular function and endothelial-glycocalyx-mitochondrial coupling can be restored early, these secondary injury processes may be minimized. The therapeutic goal is to switch the injury phenotype to a healing phenotype by reducing fluid leak and maintaining tissue O2 perfusion. Currently, no systems-based therapies exist to treat severe burns. We have been developing a small-volume fluid therapy comprising adenosine, lidocaine, and magnesium (ALM) to treat hemorrhagic shock, traumatic brain injury, and sepsis. Our early studies indicate that the ALM therapy holds some promise in supporting cardiovascular and pulmonary functions following severe burns. Future research will investigate the ability of ALM therapy to treat severe burns with polytrauma and sex disparities, and potential translation to humans.

Correlation between pupillary size and heart rate variability parameters among medical students

Autonomic nervous system controls and balances sympathetic and parasympathetic system to maintain homeostasis without conscious control. The sympathetic nervous system controls the dilation of the pupil or mydriasis. HR variation (HRV) analysis is a popular non-invasive tool for assessing functions of autonomic nervous system. Medical students are under constant cognitive load, it is required to follow-up on status on their autonomic control during their education phase. The objective of this study was to observe any correlation between pupillary size and heart rate.Total of 30 students participated in the study. Anthropometric measurements and vitals like pulse, blood pressure was recorded. Pupillary size of the participants was measured using the pupillometer in the illuminated. HRV recording was done by placing electrodes for standard Lead II ECG. HRV reports were generated using Kubios HRV 3.5 software standard version. The pupillary size Right and Left are negatively correlated with the SDNN, RMSSD, PNN50, HF, SDI and SD2. However, LF, LF/HF and SD2/SD1 ratio are positively correlated. These findings support the notion that pupillary size can serve as a non-invasive indicator of autonomic nervous system activity.

Central Nervous System, Hormonal Regulation and Sensory Control of Schooling Behavior of Fish

Central Nervous System, Hormonal Regulation and Sensory Control of Schooling Behavior of Fish

Functional neuroimaging related to lower urinary tract sensations: Future directions for study designs and selection of patient groups: ICI-RS 2023.

Neuroimaging studies have advanced our understanding of the intricate central nervous system control network governing lower urinary tract (LUT) function, shedding light on mechanisms for urine storage and voiding. However, a lack of consensus in methodological approaches hinders the comparability of results among research groups and limits the translation of this knowledge to clinical applications, emphasizing the need for standardized methodologies and clinical utilization guidelines. This paper reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities to progress the field of neuroimaging in LUT control and dysfunction. Neuroimaging holds great potential for improving our understanding of LUT control and pathophysiological conditions. To date, functional neuroimaging techniques have not yet achieved sufficient strength to make a direct clinical impact. Potential approaches that can improve the clinical utilization of neuroimaging were discussed and research questions proposed. Neuroimaging offers a valuable tool for investigating LUT control, but it's essential to acknowledge the potential for oversimplification when interpreting brain activity due to the complex neural processing and filtering of sensory information. Moreover, technical limitations pose challenges in assessing key brain stem and spinal cord centers, particularly in cases of neurological dysfunction, highlighting the need for more reliable imaging of these centers to advance our understanding of LUT function and dysfunction.

CNS Control after First-Line Osimertinib in Patients with Metastatic EGFR-Mutant NSCLC

Although osimertinib (osi) has excellent intracranial activity in EGFR-mutant metastatic non-small cell lung cancer (NSCLC), there is no consensus regarding whether to continue osi for central nervous system (CNS) control with second-line chemotherapy (chemo) at the time of systemic progression. We aimed to compare CNS outcomes after first-line osi in patients receiving second-line chemo with or without continuation of osi. We retrospectively reviewed patients with EGFR-mutant NSCLC with brain metastases (BrM) at the time of initiating first-line osi who experienced progression and started second-line chemo. Cumulative incidence of local and distant CNS progression, and extracranial (EC) progression was calculated from time of second-line chemo initiation with death as a competing risk. Overall survival (OS) was analyzed using Kaplan-Meier. We included 52 patients with a median follow up of 9.6 months (range 0.4-36.4). Median OS and CNS progression-free survival (PFS) from the time of starting second-line chemo was 12.5 months (95% CI 8.1-16.9), and 5.3 months (95% CI 3.35-7.26), respectively. The 1-year cumulative incidence of local, distant CNS progression, any CNS progression, and EC progression was 14.4% (95% CI 4.5-24.2), 42.8% (95% CI 22.8-56.8), 42.8% (95% CI 22.8-56.8) and 66.8% (95% CI 53.5-80.2), respectively. After progression on first-line osi, 25 (48.1%) and 27 patients (51.9%) continued and discontinued osi, respectively. Patients who continued osi had significantly higher BrM burden than those who did not, with 17 (68%), 3 (12%), and 5 (20%) versus 26 (96%), 0, and 1 (3.7%) patient having <10 or >11 parenchymal brain lesions, or leptomeningeal disease (LMD) at the time of second line therapy, respectively (p<0.01). In those who continued osi vs those who did not, median OS (10.8 vs 12.5 months; p = 0.37), median intracranial PFS (5.3 vs 4.8 months; p = 0.99), 1-year cumulative incidence of local (8.4% versus 20 % p = 0.26), and 1-year distant CNS progression (24.8% vs 60%; p = 0.08) was not significantly different. CNS complications such as symptomatic, hospitalizations, and steroid initiation for CNS disease, and progression of LMD were not significantly different between the two groups. Eventually, 10 patients underwent salvage RT post first-line osi and median time to salvage RT was 7.8 months (range 2-9.4). Of patients who underwent salvage RT, 2 patients (20%) had continued osi with second-line chemo. Twelve patients (44.4%) who did not continue osi eventually re-started osi for progressive disease. Patients who continued osi had significantly higher BrM tumor burden. Despite these patients being at higher risk for CNS progression, time to CNS progression and incidence of CNS complications were not significantly different in the two cohorts. Patients who discontinued osi were more likely to undergo salvage RT. Continuation of osi may allow patients to defer salvage RT.

Blink Reflex Examination in Patients with Amyotrophic Lateral Sclerosis Compared to Diseases Affecting the Peripheral Nervous System and Healthy Controls.

Amyotrophic lateral sclerosis (ALS) is a fatal form of neuromuscular disease. The aim of this study was to assess changes in the blink reflex (BR) parameters as a valid and easy-to-use tool in ALS patients. We assessed the BR test in patients with a definitive diagnosis of ALS, healthy volunteers, and patients with diseases affecting the peripheral nervous system. The BR was studied in 29 patients who met the Awaji criteria. Latencies were compared with our healthy controls (N = 50) and other diseases of the peripheral nervous system (N = 61). The ALS Functional Rating Scale-Revised (ALSFRS-R) was used to evaluate functional status. Significantly prolonged R2i and R2c latencies were found in the ALS group compared with the healthy control group (p < 0.001). The latencies of R1, R2i, R2c were all increased in the bulbar subtype compared to the limb-onset subtype (p < 0.05). According to our results, BR examination might be a promising tool to monitor the course of the disease or serve as a prognostic biomarker in patients with ALS, but it should be assessed in further studies. The abnormalities detected through BR might help perform earlier interventions in ALS patients and might be useful in other diseases affecting the peripheral nervous system.