Reflex Latency Research Articles

Early Electrophysiology in Suspected Acute Guillain-Barré Syndrome: A Prospective Study of Comprehensive Testing.

Electrophysiologic changes in early Guillain-Barré Syndrome (GBS) can be nondiagnostic. Improved testing paradigms may improve hyperacute treatment. This work prospectively evaluated consecutive patients admitted to a metropolitan teaching hospital in Melbourne, Australia, with suspected acute GBS. We performed extensive neurophysiology at three different time points. Novel tests, including cutaneous silent periods, long latency reflexes, and contraction-induced H reflexes, were assessed. Twenty-three participants were studied, including 13 cases of acute GBS. In total, 69% of acute cases of GBS were accurately diagnosed on the first nerve conduction study using published neurophysiologic criteria, with serial studies rarely altering the GBS subtype classification. Antidromic and orthodromic upper limb sensory studies were diagnostically equivalent. A sural sparing pattern was seen in 77% of cases of GBS at the first test. Long latency reflexes and contraction-induced H reflexes testing were abnormal in most participants but were limited by muscle weakness in some. Cutaneous silent periods testing was unobtainable in approximately 50% of cases because of weakness and did not discriminate from mimic disorders. Abnormalities of long latency reflexes and contraction-induced H reflexes may be helpful where initial electrophysiology is nondiagnostic but are nonspecific. Cutaneous silent periods testing seems of limited value. Comprehensive testing provides diagnostic certainty in most cases of GBS from the very first study.

Methylphenidate Reversal of Dexmedetomidine-Induced Versus Ketamine-Induced Sedation in Rats.

Dexmedetomidine and ketamine have long elimination half-lives in humans and have no clinically approved reversal agents. Methylphenidate enhances dopaminergic and noradrenergic neurotransmission by inhibiting reuptake transporters for these arousal-promoting neurotransmitters. Previous studies in rats demonstrated that intravenous methylphenidate induces emergence from isoflurane and propofol general anesthesia. These 2 anesthetics are thought to act primarily through enhancement of inhibitory Gamma-aminobutyric acid type A (GABAA) receptors. In this study, we tested the behavioral and neurophysiological effects of methylphenidate in rats after low and high doses of dexmedetomidine (an alpha-2 adrenergic receptor agonist) and ketamine (an N-methyl-D-aspartate [NMDA] receptor antagonist) that induce sedation and unconsciousness, respectively. All experiments used adult male and female Sprague-Dawley rats (n = 32 total) and all drugs were administered intravenously in a crossover, blinded experimental design. Locomotion after sedating doses of dexmedetomidine (10 µg/kg) or ketamine (10 mg/kg) with and without methylphenidate (5 mg/kg) was tested using the open field test (n = 16). Recovery of righting reflex after either high-dose dexmedetomidine (50 µg/kg) or high-dose ketamine (50 mg/kg) with and without methylphenidate (1-5 mg/kg) was assessed in a second cohort of rats (n = 8). Finally, in a third cohort of rats (n = 8), frontal electroencephalography (EEG) was recorded for spectral analysis under both low and high doses of dexmedetomidine and ketamine with and without methylphenidate. Low-dose dexmedetomidine reduced locomotion by 94% in rats. Methylphenidate restored locomotion after low-dose dexmedetomidine (rank difference = 88.5, 95% confidence interval [CI], 70.8-106) and the effect was blocked by coadministration with a dopamine D1 receptor antagonist (rank difference = 86.2, 95% CI, 68.6-104). Low-dose ketamine transiently attenuated mobility by 58% and was not improved with methylphenidate. Methylphenidate did not affect the return of righting reflex latency in rats after high-dose dexmedetomidine nor ketamine. Frontal EEG analysis revealed that methylphenidate reversed spectral changes induced by low-dose dexmedetomidine (F [8,87] = 3.27, P = .003) but produced only transient changes after high-dose dexmedetomidine. Methylphenidate did not induce spectral changes in the EEG after low- or high-dose ketamine. Methylphenidate reversed behavioral and neurophysiological correlates of sedation, but not unconsciousness, induced by dexmedetomidine. In contrast, methylphenidate did not affect sedation, unconsciousness, nor EEG signatures in rats after ketamine. These findings suggest that methylphenidate may be efficacious to reverse dexmedetomidine sedation in humans.

Enhancing sciatic nerve regeneration with osteopontin-loaded acellular nerve allografts in rats: Effects on macrophage polarization

Osteopontin (OPN) is a multifunctional matrix glycoprotein with neuroprotective and immunomodulatory properties. This study explored the potential of OPN-loaded acellular nerve allografts (ANAs) to repair sciatic nerves in male Wistar rats. The research also delved into the impact of OPN on macrophage phenotypes. We reconstructed a 10 mm nerve gap with ANAs containing OPN at 2 nM and 4 nM. The sciatic functional index (SFI) and paw withdrawal reflex latency (WRL) showed the significant efficacy of ANA/OPN (2 nM) in enhancement of target organ reinnervation and subsequent sensorimotor recovery compared to other groups. Electrophysiological and histomorphometric analyses further supported the regenerative properties of ANA/OPN (2 nM). Additionally, ANA/OPN (2 nM) promoted macrophage polarization towards an M2 phenotype and reduced proinflammatory cytokines at the injury site. In conclusion, the study suggested that ANA loaded with 2 nM OPN effectively repaired transected sciatic nerves in rats, potentially through enhancing axonal sprouting and exerting anti-inflammatory effects.

Laser acupuncture and photobiomodulation therapy in Bell’s palsy with a duration of greater than 8 weeks: a randomized controlled trial

To investigate the efficacy of laser acupuncture and photobiomodulation therapy in alleviating symptoms among patients diagnosed with Bell’s palsy with duration of greater than 8 weeks. The randomized controlled trial has been performed from May 2021 to April 2023. Patients were eligible who had Bell’s palsy with duration of greater than 8 weeks on out-patient Department of Otorhinolaryngology in Beijing Tongren Hospital. The laser acupuncture group received class IV laser treatment for 3 times per weeks, a total of 72 times. The control group received the same treatment procedure except the laser parameter. The primary outcome measures comprised House–Brackmann facial nerve grading system and electroneurography. Secondary outcome measures comprised Sunnybrook facial grading system, electromyography, and the blink reflex. A total of 84 participants were included (42 control group, 42 laser acupuncture group). After treatment, House–Brackmann facial nerve grading system (OR, 0.11; 95% CI, 0.04–0.30; P < 0.001), and the pathologic numbers of electroneuronography were statistically different between the laser acupuncture group and control group, including orbicularis oculi (OR,0.08; 95% CI, 0.02–0.21; P < 0.001), Frontalis muscle (OR,0.14; 95% CI, 0.05–0.39; P < 0.001), Orbicularis oris (OR,0.13; 95% CI, 0.04–0.36; P < 0.001), Ala nasi muscle (OR,0.06; 95% CI, 0.02–0.18; P < 0.001). In secondary outcomes, Sunnybrook facial grading system, has significant difference between the two groups (20.26; 95% CI, 14.69 to 25.83; P < 0.01). Latency by ENoG, include orbicularis oculi (-0.61; 95% CI, -0.43 to -0.09; P < 0.001), frontalis muscle (-0.12; 95% CI, -0.21 to -0.03; P < 0.01), orbicularis oris (-0.28; 95% CI, -0.41 to -0.16; P < 0.001), and ala nasi muscle (-0.26; 95% CI, -0.38 to -0.16; P < 0.001). All amplitudes of MUAPs and durations by electromyography (EMG) showed statistically significant differences compared with the control group after treatment. For the frontalis muscle, the amplitude of MUAPs was -64.23 (95% CI, -80.89 to -47.56; P < 0.001) and duration was -1.18 (95% CI, -1.49 to -0.87; P < 0.001). For orbicularis oris, amplitude of MUAPs was -29.82 (95% CI, -55.03 to -4.62; P = 0.02) and duration was -0.57 (95% CI, -0.94 to -0.20; P < 0.001). For depressor angulli oris, amplitude of MUAPs was -47.06 (95% CI, -62.15 to -31.97; P < 0.001) and duration was -2.21 (95% CI, -2.69 to -1.72; P < 0.001). Blink reflex, including R1 (OR, 0.03; 95% CI, 0.01–0.16; P < .001), R2 (OR, 0.04; 95% CI, 0.004–0.29; P < .001), and R2 latency differences (OR, 0.15; 95% CI, 0.05–0.51; P < .001), have significant difference between the two groups, respectively. The findings suggest that laser acupuncture relieve symptoms for patients with Bell’s palsy with a duration of greater than 8 weeks.Trial registration: ClinicalTrials.gov Identifier: NCT05846217.

Evaluation of Brain Stem Function in Diabetics with and Without Distal Symmetrical Polyneuropathy Using the Blink Reflex

Background: Diabetic peripheral neuropathy (DPN) is the commonest complication of T2DM. Neuropathy is a descriptor for a spectrum of clinical and subclinical symptoms with varying anatomical distributions, clinical histories, and perhaps underlying pathogenetic mechanisms. The distal Symmetrical sensory polyneuropathy is chronic, symmetrical, length-dependent sensorimotor. Studies of the blink reflex have shown potential as a method of assessing brainstem activity. Objective: The primary purpose of this research was to assess the function of the blink reflex in the early detection of cranial nerves and brain stem dysfunction in diabetes patients with and without polyneuropathy. We also aimed to see whether there were differences in blink reflex abnormalities between diabetes individuals with and without polyneuropathy. Patients and Methods: The study included a group of sixty-60 diabetic patients. Clinician and electrophysiologist evaluations were used to determine the severity of neuropathy. Patients with diabetes were separated into two groups: those with and without neuropathy. Results: A statistically significant difference between the two groups was for C.R.2 latency, and I.R.2 latency with a P-value &lt;0.001. Except for blink reflex’s R1 latency (P-value &gt;0.2), all other Blink reflex parameters were statistically different between patients who experience diabetic neuropathy and those who didn’t. Regarding HbA1c, a significant positive association with IR2 latency and C.R.2 latency was noted (Pvalue &lt;0.001) and also, a statistically significant negative association was found with I.R.2 duration and C.R.2 duration (P-value &lt;0.001). Amplitudes of sural, tibial and peroneal nerves were negatively associated with Blink reflex Latencies and positively associated with blink reflex duration. Conclusion: In conclusion, blink-reflex parameters (including ipsi-lateral R.2 latency, contra-lateral R.2 latency) are significantly associated with HBA1C level and degree of peripheral diabetic neuropathy. Received Sept. 2022 Accepted Nov. 2023 Published Jan. 2024

Familial adult myoclonus epilepsy: a pragmatic approach.

Familial Adult Myoclonus Epilepsy (FAME), with a prevalence of < 1/35 000,is known under different acronyms. The disease is transmitted in an autosomal dominant manner and is characterized by the occurrence of cortical myoclonic tremor, overt myoclonus, and rare bilateral tonic-clonic seizures. FAME is considered neurodegenerative, although it is relatively slow in progression. Diagnosis is based on specific neurophysiological testing, namely jerk-locked back-averaging, somatosensory evoked potentials, long latency reflex, and motor evoked potentials, among others.Imaging data, including functional magnetic resonance imaging, indicate a cortical origin of the cortical myoclonic tremor and decreased cerebellar activation.Cerebellar changes in Purkinje cells have beennoted,from few neuropathology reports, in patients from isolated pedigrees. The differential diagnosis includes essential tremor, some forms of genetic generalized epilepsy, and progressive myoclonus epilepsies. Treatment is mainly symptomatic.

Epothilone B loaded in acellular nerve allograft enhanced sciatic nerve regeneration in rats.

Epothilone B (EpoB) is a microtubule-stabilizing agent with neuroprotective properties. This study examines the regenerative properties of ANA supplemented with EpoB on a sciatic nerve deficit in male Wistar rats. For this purpose, the 10mm nerve gap was filled with acellular nerve allografts (ANAs) containing EpoB at 0.1, 1, and 10nM concentrations. The sensorimotor recovery was evaluated up to 16 weeks after the operation. Real-time PCR, histomorphometry analysis, and electrophysiological evaluation were also used to evaluate the process of nerve regeneration. ANA/EpoB (0.1nM) significantly improved sensorimotor recovery in rats compared to ANA, ANA/EpoB (1nM), and ANA/EpoB (10nM) groups. This led to reduced muscle atrophy, improved sciatic functional index, and thermal paw withdrawal reflex latency, indicating nerve regeneration and target organ reinnervation. The electrophysiological and histomorphometry findings also confirmed the ANA/EpoB regenerative properties (0.1nM). EpoB only enhanced ANA regenerative properties at 0.1nM, with no therapeutic effects at higher concentrations. Totally, we concluded that ANA loaded with 0.1nM EpoB can effectively reconstruct the transected sciatic nerve in rats, likely by enhancing axonal sprouting and extension.

Long latency reflexes of the median nerves in healthy adults.

Long latency reflexes (LLRs) are late responses in nerve conduction studies seen after peripheral nerve stimulation during submaximal muscle contraction. They follow a short latency reflex, also known as the H reflex, and are thought to involve transcortical pathways, providing a measure of proximal nerve and central conduction. For this reason, they have been evaluated in several central nervous system diseases, but reference values are not widely published and are mostly based on old studies with very small numbers of participants. Therefore, in this work we aim to provide comprehensive reference values for LLR testing. LLRs were tested in a cohort of 100 healthy participants, testing the median nerve bilaterally. Mean latencies for short latency reflex (SLR), LLR1, LLR2, and LLR3 were 27.00, 38.50, 47.60, and 67.34 milliseconds, respectively. The allowable side-to-side difference was approximately 3 to 4 milliseconds. No significant sex-related differences were seen. Height correlated moderately with the SLR latency, but only weakly with LLR1, LLR2, and LLR3. This work provides normal LLR values for comparison with future studies in disease. The technique used may allow for improved evaluation of central nervous system or proximal peripheral nerve disorders.

Magnitude, variability and symmetry in head acceleration and jerk and their relationship to cervical and ocular vestibular evoked myogenic potentials.

Acceleration and changes in acceleration (jerk) stimulate vestibular otolith afferents. Bone-conducted (BC) vibration applied to the skull accelerates the head and produces short latency reflexes termed vestibular evoked myogenic potentials (VEMPs). To determine the magnitude, variability and symmetry in head acceleration/jerk during VEMP recordings and investigate the relationship between head acceleration/jerk and VEMP properties. 3D head accelerometery (sagittal, interaural and vertical axes) was recorded bilaterally in thirty-two healthy subjects during cervical (cVEMP) and ocular (oVEMP) recordings. BC 500 Hz sinusoidal tones were applied to the midline forehead using a positive polarity stimulus. The direction of induced acceleration/jerk was predominately backward, outward and downward on either side of the head during cVEMP and oVEMP recordings.Overall, acceleration/jerk was larger in the sagittal and interaural axes and peaked earlier in the interaural axis bilaterally. Acceleration was more symmetric in the sagittal and interaural axes whereas jerk symmetry did not differ between axes. Regression models did not show a systematic relationship between acceleration/jerk and either VEMP reflex. The pattern of skull acceleration/jerk was relatively consistent between the two sides of the head and across subjects, but there were differences in magnitude, leading to inter-side and inter-subject variability.

Transspinal Focused Ultrasound Suppresses Spinal Reflexes in Healthy Rats

ObjectivesLow-intensity, focused ultrasound (FUS) is an emerging noninvasive neuromodulation approach, with improved spatial and temporal resolution and penetration depth compared to other noninvasive electrical stimulation strategies. FUS has been used to modulate circuits in the brain and the peripheral nervous system, however, its potential to modulate spinal circuits is unclear. In this study, we assessed the effect of trans-spinal FUS (tsFUS) on spinal reflexes in healthy rats. Materials and MethodstsFUS targeting different spinal segments was delivered for 1 minute, under anesthesia. Monosynaptic H-reflex of the sciatic nerve, polysynaptic flexor reflex of the sural nerve, and withdrawal reflex tested with a hot plate were measured before, during, and after tsFUS. ResultstsFUS reversibly suppresses the H-reflex in a spinal segment-, acoustic pressure- and pulse-repetition frequency (PRF)-dependent manner. tsFUS with high PRF augments the degree of homosynaptic depression of the H-reflex observed with paired stimuli. It suppresses the windup of components of the flexor reflex associated with slower, C-afferent, but not faster, A- afferent fibers. Finally, it increases the latency of the withdrawal reflex. tsFUS does not elicit neuronal loss in the spinal cord. ConclusionsOur study provides evidence that tsFUS reversibly suppresses spinal reflexes and suggests that tsFUS could be a safe and effective strategy for spinal cord neuromodulation in disorders associated with hyperreflexia, including spasticity after spinal cord injury and painful syndromes.

PupillOmetry for preDIction of DeliriUM in ICU (PODIUM): protocol for a prospective multicentre cohort study

IntroductionDelirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate...

Comparison of the blink reflex in classical and idiopathic trigeminal neuralgia

Background Previous findings indicate that the blink reflex is useful to distinguish between primary (classical/idiopathic) and secondary trigeminal neuralgia. No prior studies have investigated whether the blink reflex could identify differences in electrophysiological responses between classical and idiopathic trigeminal neuralgia. With this in mind, we investigated the blink reflex in a cohort of classical and idiopathic trigeminal neuralgia patients. Methods Participants were consecutively enrolled in the study. According to magnetic resonance imaging findings, the patients were subgrouped into either classical or idiopathic trigeminal neuralgia. Assessors were blinded to the subgroup and pain side, and the blink reflex was examined to assess R1 and R2 latencies, as well as the area under the curve. Results The study group constituted of 55 patients with primary trigeminal neuralgia: 25 patients with classical trigeminal neuralgia and 30 patients with idiopathic trigeminal neuralgia. None of the blink reflex latencies (R1 and R2) or the area under the curve significantly differed between the two subgroups when adjusted for age and sex ( p &gt; 0.05). Conclusions Our findings suggest that the blink reflex cannot be used to differentiate classical and idiopathic trigeminal neuralgia patients, and that both subgroups may share common pathophysiological mechanisms. Trial Registration: ClinicalTrials.gov Identifier: NCT05328661.

Evaluation of outcome of acoustic reflex tests in patients with type 2 diabetes mellitus: a cross-sectional study

PurposeType 2 diabetes mellitus (T2DM) may induce micro-vascular and macro-vascular changes that can lead to neuropathic changes which may affect the auditory pathway resulting in hearing loss. The study aims to evaluate the outcome of ipsilateral and contralateral acoustic reflex (AR) parameters and reflex decay tests (RDT) in patients with T2DM, and the relationship between average AR parameters, and duration and control of T2DM.MethodsAn analytical cross-sectional study was conducted in a tertiary care setup in 126 subjects which included 42 subjects with T2DM between 30 and 60 years of age, age-matched with 84 non-diabetic subjects. The subjects were evaluated for pure tone average (PTA), speech identification score (SIS), AR parameters [acoustic reflex threshold (ART), acoustic reflex amplitude (ARA), acoustic reflex latency (ARL)] and RDT.ResultsThe subjects with T2DM showed increased PTA in both ears when compared to the subjects with no disease. No significant difference was found in the SIS between both groups. There was no significant difference in the ART and ARL between the two groups. There was a significant difference in the ipsilateral and contralateral ARA at 500 Hz, 1000 Hz and broadband noise (BBN) when compared between the diabetic and non-diabetic groups. No significant difference was found between average AR parameters and duration and control of T2DM.ConclusionT2DM increases hearing thresholds and reduces ipsilateral and contralateral AR at lower frequencies and BBN. Duration and control of T2DM do not affect the AR parameters.

(040) A Case Report of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia Secondary to Lumbar Facet Cyst-Induced Sacral Radiculopathy Treated by Lumbar Endoscopic Spine Surgery

Abstract Introduction Persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD), characterized by distressing, abnormal genito-pelvic sensations, especially unwanted genital arousal, may be triggered by pathology in Region 3, the cauda equina. Sacral radiculopathy is an inflammatory irritation of the S2-S3 nerve roots in the cauda equina, formed by convergence of pelvic, pudendal, and sciatic nerves and clinical symptoms that involve the sensory fields of these nerves. In a subgroup of patients, both cauda equina Tarlov cyst-induced sacral radiculopathy and lumbosacral annular tear-induced sacral radiculopathy have been reported to trigger PGAD/GPD, and in both conditions, endoscopic spine surgery has been shown safe and effective. Lumbar facet cysts, most common at the L4-L5 level, arise from lumbar zygapophyseal joints and can cause sacral radiculopathy. Thus, it is possible that lumbar facet cyst-induced sacral radiculopathy may be a trigger for PGAD/GPD. Objective To report one case of PGAD/GPD secondary to lumbar facet cyst-induced sacral radiculopathy, successfully treated with lumbar endoscopic spine surgery (LESS). Methods A 55-year old woman with a long history of PGAD/GPD presented to our spine-sexual medicine program for biopsychosocial assessment and treatment using our multidisciplinary management algorithm: Step A) detailed psychosocial and medical history; Step B) non-invasive assessments for sacral radiculopathy; Step C) targeted diagnostic transforaminal epidural spinal injection (TFESI) resulting in temporary clinically significant reduction of PGAD/GPD symptoms; Step D) surgical intervention with LESS and post-operative multidisciplinary follow-up. The patient was diagnosed with PGAD/GPD from lumbar facet cyst-induced sacral radiculopathy and underwent LESS for an L4-5 facet cyst. Results This 55 year old cisgendered woman had multiple painful spontaneous orgasms, shooting sharp pains that felt “like a bruise” going up the inside of her vagina, hypersensitivity of her vulva, clitoris, vagina, urethra and anus, along with constant symptoms of arousal and urinary urgency. These began in 2008 after her second childbirth. Her PGAD symptoms worsened over the last 2 years. She experienced sensations of pins and needles in her right buttocks, front of her left thigh, and down both legs into feet and toes. She also had severe constipation and restless leg syndrome. Neurogenital testing, including quantitative sensory testing, sacral dermatome testing and bulbocavernosus reflex latency testing, were all abnormal consistent with sacral radiculopathy. Region 1 anesthesia testing for vestibular pain showed persistent PGAD/GPD symptoms despite numbness on vestibular cotton swab testing. Pudendal nerve testing was negative. It was thus hypothesized that her PGAD/GPD trigger was closer to the central nervous system. Her MRI showed an L4-5 facet cyst. A TFESI with anesthetic was positive with temporary symptom reduction. She underwent LESS to excise the facet cyst and was discharged the same day. At early post-operative follow-up, she is PGAD-free. She no longer has irritative bladder symptoms, sciatica, restless leg syndrome, or pins and needles, and her constipation symptoms have improved. Conclusions Of the many recognized triggers for PGAD/GPD, we report for the first time a patient diagnosed with lumbar facet cyst-induced sacral radiculopathy after a multidisciplinary step-care management algorithm evaluation. She experienced marked improvement with lumbar endoscopic spine surgery. Disclosure No

The role of sural nerve reflexes during drop-landing in subjects with and without chronic ankle instability

The purpose of this study was to investigate the functional role of cutaneous reflexes during a single-leg drop-landing task among healthy, neurologically intact adults, and to identify whether individuals with chronic ankle instability (CAI) demonstrate altered reflexes and subsequent ankle kinematics. All subjects were physically active adults and were categorized as control (n = 10, Male = 6, Female = 4) or CAI (n = 9, Male = 4, Female = 5) depending on whether they scored a 0 or ≥ 11 on the Identification of Functional Ankle Instability questionnaire, respectively. Subjects performed 30-40 single-leg drop-landing trials from a platform set to the height of their tibial tuberosity. Muscle activity of four lower leg muscles was collected via surface electromyography, while ankle kinematics were recorded via an electrogoniometer. Non-noxious stimulations were elicited randomly to the ipsilateral sural nerve at two unique phases of the drop-landing task (takeoff and landing). Unstimulated and stimulated trials were used to calculate middle latency reflex amplitudes (80-120ms) and net ankle kinematics (140-220ms) post-stimulation. Mixed-factor ANOVAs were used to identify significant reflexes within groups and differences in reflex amplitudes between groups. Unlike the CAI group, the control group experienced significant facilitation of the Peroneus Longus (PL) and inhibition of the Lateral Gastrocnemius (LG) when stimulated at takeoff, resulting in eversion immediately prior to landing. When stimulated at landing, the control group experienced significantly more inhibition of the PL compared to the CAI group (p = 0.019). These results suggest lower neural excitability for individuals with CAI, which may predispose them to recurrent injury during similar functional tasks.

3, 3’-diindolylmethane enhances macrophage efferocytosis and subsequently relieves visceral pain via the AhR/Nrf2/Arg-1-mediated arginine metabolism pathway

Background3, 3’-diindolylmethane (DIM), a classical aryl hydrocarbon receptor (AhR) agonist, has been shown to relieve neuropathic pain, but few studies have reported the efficacy of DIM in visceral pain under colitis condition. PurposeThis study aimed to investigate the effect and mechanism of DIM on visceral pain under colitis condition. MethodsCytotoxicity was performed using the MTT assay. RT-qPCR and ELISA assays were applied to determine the expression and release of algogenic substance P (SP), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Flow cytometry was used to examine the apoptosis and efferocytosis. The expression of Arg-1-arginine metabolism-related enzymes was detected using western blotting assays. ChIP assays were used to examine the binding of Nrf2 to Arg-1. Mouse models of dextran sulfate sodium (DSS) were established to illustrate the effect of DIM and validate the mechanism in vivo. ResultsDIM did not directly affect expressions and release of algogenic SP, NGF and BDNF in enteric glial cells (EGCs). However, when co-cultured with DIM-pre-treated RAW264.7 cells, the release of SP and NGF was decreased in lipopolysaccharides-stimulated EGCs. Furthermore, DIM increased the number of PKH67+ F4/80+ cells in the co-culture system of EGCs and RAW264.7 cells in vitro and alleviated visceral pain under colitis condition by regulating levels of SP and NGF as well as values of electromyogram (EMG), abdominal withdrawal reflex (AWR) and tail-flick latency (TFL) in vivo, which was significantly inhibited by efferocytosis inhibitor. Subsequently, DIM was found to down-regulate levels of intracellular arginine, up-regulate levels of ornithine, putrescine and Arg-1 but not extracellular arginine or other metabolic enzymes, and polyamine scavengers reversed the effect of DIM on efferocytosis and release of SP and NGF. Moving forward, Nrf2 transcription and the binding of Nrf2 to Arg-1-0.7 kb was enhanced by DIM, AhR antagonist CH223191 abolished the promotion of DIM on Arg-1 and efferocytosis. Finally, nor-NOHA validated the importance of Arg-1-dependent arginine metabolism in DIM-alleviated visceral pain. ConclusionDIM enhances macrophage efferocytosis in an arginine metabolism-dependent manner via “AhR-Nrf2/Arg-1” signals and inhibits the release of SP and NGF to relieve visceral pain under colitis condition. These findings provide a potential therapeutic strategy for the treatment of visceral pain in patients with colitis.

Diagnosis and Treatment of Cauda Equina Arachnoiditis, a Rare Manifestation of Tuberculosis Meningoencephalitis: A Case Report

Tuberculous meningoencephalitis (TM) is an acute, progressive form of tuberculosis (TB). The epidemiology, clinical signs, and diagnosis of TB are well established, but several atypical forms of tuberculous spinal arachnoiditis can be easily misdiagnosed. We report a rare case of TM with cauda equina arachnoiditis diagnosed by magnetic resonance imaging and an electrodiagnostic study. A 26-year-old otherwise healthy male patient experienced fever, headache, gait disturbance, and bladder and bowel incontinence. Needle electromyography (EMG) recordings were suggestive of bilateral diffuse lumbar and lumbosacral polyradiculopathy, and the pudendal sensory-evoked potential and bulbocavernosus reflex latencies were prolonged. Lumbar arachnoiditis is a rare clinical condition that warrants a heightened index of suspicion. It has diverse etiologies and symptoms, and it can lead to potentially serious and irreversible disorders. This case illustrates the usefulness of nerve conduction, EMG, and pudendal sensory-evoked potential and bulbocavernosus reflex latency studies in the diagnosis of cauda equina syndrome induced by TB arachnoiditis.

Differences in Trapezius Muscle H-Reflex between Asymptomatic Subjects and Symptomatic Shoulder Pain Subjects.

In chronic shoulder pain, adaptations in the nervous system such as in motoneuron excitability, could contribute to impairments in scapular muscles, perpetuation and recurrence of pain and reduced improvements during rehabilitation. The present cross-sectional study aims to compare trapezius neural excitability between symptomatic and asymptomatic subjects. In 12 participants with chronic shoulder pain (symptomatic group) and 12 without shoulder pain (asymptomatic group), the H reflex was evoked in all trapezius muscle parts, through C3/4 nerve stimulation, and the M-wave through accessory nerve stimulation. The current intensity to evoke the maximum H reflex, the latency and the maximum peak-to-peak amplitude of both the H reflex and M-wave, as well as the ratio between these two variables, were calculated. The percentage of responses was considered. Overall, M-waves were elicited in most participants, while the H reflex was elicited only in 58-75% or in 42-58% of the asymptomatic and symptomatic participants, respectively. A comparison between groups revealed that the symptomatic group presented a smaller maximum H reflex as a percentage of M-wave from upper trapezius and longer maximal H reflex latency from the lower trapezius (p < 0.05). Subjects with chronic shoulder pain present changes in trapezius H reflex parameters, highlighting the need to consider trapezius neuromuscular control in these individuals' rehabilitation.

Fascicle dynamics of the tibialis anterior muscle reflect whole-body walking economy

Humans can inherently adapt their gait pattern in a way that minimizes the metabolic cost of transport, or walking economy, within a few steps, which is faster than any known direct physiological sensor of metabolic energy. Instead, walking economy may be indirectly sensed through mechanoreceptors that correlate with the metabolic cost per step to make such gait adaptations. We tested whether velocity feedback from tibialis anterior (TA) muscle fascicles during the early stance phase of walking could potentially act to indirectly sense walking economy. As participants walked within a range of steady-state speeds and step frequencies, we observed that TA fascicles lengthen on almost every step. Moreover, the average peak fascicle velocity experienced during lengthening reflected the metabolic cost of transport of the given walking condition. We observed that the peak TA muscle activation occurred earlier than could be explained by a short latency reflex response. The activation of the TA muscle just prior to heel strike may serve as a prediction of the magnitude of the ground collision and the associated energy exchange. In this scenario, any unexpected length change experienced by the TA fascicle would serve as an error signal to the nervous system and provide additional information about energy lost per step. Our work helps provide a biomechanical framework to understand the possible neural mechanisms underlying the rapid optimization of walking economy.

High-frequency whole-body vibration activates tonic vibration reflex.

The aim of this research was to examine whether high-frequency whole-body vibration activates the tonic vibration reflex (TVR). The experimental study was conducted with seven volunteers (mean age: 30.8±3.3 years; range, 26 to 35 years) between December 2021 and January 2022. To elicit soleus TVR, high-frequency (100-150 Hz) vibration was applied to the Achilles tendon. High-frequency (100-150 Hz) whole-body vibration and low-frequency (30-40 Hz) whole-body vibration were applied in quiet standing. Whole-body vibration-induced reflexes were recorded from the soleus muscle using surface electromyography. The cumulative average method was used to determine the reflex latencies. Soleus TVR latency was 35.6±5.9 msec, the latency of the reflex activated by high-frequency whole-body vibration was 34.8±6.2 msec, and the latency of the reflex activated by low-frequency whole-body vibration was 42.8±3.4 msec (F(2, 12)=40.07, p=0.0001, ƞ2 =0.87). The low-frequency whole-body vibration-induced reflex latency was significantly longer than high-frequency whole-body vibration-induced reflex latency and TVR latency (p=0.002 and p=0.001, respectively). High-frequency whole-body vibration-induced reflex latency and TVR latency were found to be similar (p=0.526). This study showed that high-frequency whole-body vibration activates TVR.