Unraveling the stride: exploring the influence of neurogenic orthostatic hypotension on gait and balance in Parkinson's disease.

PURPOSE: Neurogenic orthostatic hypotension (nOH) and gait impairment are frequent sources of disability in Parkinson's disease (PD). However, the impact of nOH on balance and gait features remains unclear. This cross-sectional study aimed to assess the influence of nOH on postural and gait parameters in a cohort of patients with PD by means of wearable inertial sensors. METHODS: Gait and balance were assessed using Opal inertial sensors. nOH was defined as sustained systolic blood pressure (BP) drop ≥ 20 mmHg or diastolic BP drop ≥ 10 mmHg within 3 min of standing, with a ΔHR/ΔSBP ratio ≤ 0.5 bpm/mmHg. Analysis of covariance was performed to evaluate differences in gait/balance features between patients with and without nOH, adjusting for age, cognitive status, and motor disability. Moreover, we performed the same analysis considering the presence of hemodynamically relevant nOH (orthostatic mean BP ≤ 75 mmHg). RESULTS: A total of 82 patients were enrolled, 26 with nOH (31.7%), of which 13 presented with hemodynamically relevant nOH. After correcting for confounders, nOH was independently associated with lower gait speed (p = 0.027), shorter stride length (p = 0.033), longer time for postural transitions (p = 0.004), and increased postural sway (p = 0.019). These differences were even more pronounced in patients with hemodynamically relevant nOH. Higher postural sway was associated with a 7.9-fold higher odds of falls (p = 0.040). CONCLUSIONS: Our study presents an objective demonstration of the independent negative impact of nOH on gait and balance in PD, emphasizing the need for careful detection and management of nOH to mitigate gait and balance disturbances in PD.

Ureteroscopy for stone disease in pediatric patients with neurogenic bladder: A single institution case-control study.

INTRODUCTION: Ureteroscopy (URS) for urolithiasis in pediatric patients may be particularly challenging for patients with co-morbidities that increase the risk for stone formation and recurrence. Patients with neurogenic bladders (NGB) and/or patients that are non-ambulatory are reported to have higher rates of additional comorbidities and a particularly increased risk of developing urolithiasis, and higher rates of infections and post-operative complications. OBJECTIVE: To report outcomes of URS for stone disease in pediatric patients with NGB and/or non-ambulatory status and compare these outcomes to patients without these co-morbidities. METHODS: An IRB-approved prospective single institutional registry was used to retrospectively identify all patients under 18 years of age who underwent URS for stone disease between July 2012 and July 2021, excluding bladder stones. Patients were categorized in two groups: patient with NGB with or without non-ambulatory status versus all other patients (control). Baseline demographics, pre-operative radiologic imaging, intra-operative details, and post-operative outcomes including 30-day complications were aggregated and compared between the two groups. RESULTS: 275 URS in 198 patients were performed during the study period, and 49 (18 %) of these were performed on patients with NGB. Pre-operative imaging showed significantly higher number of stones (3 vs 2, p = 0.003) and larger total stone burden in patients with NGB than those without NGB (15 mm vs 9 mm, p = 0.009). Patients with NGB had a significantly longer length of procedure (86 vs 60 min, p = 0.002), increased need for staged procedures, increased length of stay (1 vs 0 days, p < 0.001), and increased use of an extended duration of antibiotics prior to the procedure (<0.001). There was no difference in need for passive dilation, stent placement, or other intra-operative parameters. There was no statistical difference in the incidence of 30-day complications between the two groups post-operatively. However, there was a higher incidence of febrile UTIs (8.2 % vs 1.3 %, p = 0.021) in patients with NGB and a lower incidence of pain related complications (0 % vs 9.3 %, p = 0.032). Patients with NGB had a higher incidence of requiring ipsilateral URS for recurrent stone disease within a year of surgery (34.6 % vs 18.9 %, p = 0.01). CONCLUSION: The results show that URS for urolithiasis can be done safely and effectively in pediatric patients with neurogenic bladders. The increased risk of infectious complications within 30 days of surgery warrants careful pre- and post-operative antibiotic care plan for this patient population.

Human Molecular Mechanisms of Discogenic Low Back Pain: A Scoping Review.

The limited understanding of the mechanisms underlying human discogenic low back pain (DLBP) has hampered the development of effective treatments. While there is much research on disc degeneration, the association between degeneration and pain is weak. Therefore, there is an urgent need to identify pain-inducing molecular mechanism to facilitate the development of mechanism-specific therapeutics. This scoping review aims to determine the current knowledge of molecular mechanisms associated with human DLBP. A systematic search on CENTRAL, CINAHL, Citation searching, ClinicalTrials.gov, Embase, Google Scholar, MEDLINE, PsycINFO, PubMed, Scopus, Web of Science, and World Health Organization was performed. Studies with human DLBP as diagnosed by discography or imaging that analyzed human disc tissues and reported pain-related outcomes were included, and those on predominant radicular pain were excluded. The search returned 6,012 studies. Most studies did not collect pain-related outcomes. Those that included pain assessment relied on self-report of pain intensity and disability. Six studies qualified for data extraction and synthesis. The main molecular mechanisms associated with DLBP were the expressions of nociceptive neuropeptides and cytokines, particularly TNF-αdue to its strong association with pain outcomes. Activation of NF-κB signaling pathway, alterations in adrenoceptor expressions, and increase in reactive oxygen species (ROS) were also associated with DLBP through regulation of pro-inflammatory factors and pain-related neuropeptides. Current evidence converges to TNF-α, NF-κB signaling, and ROS-induced pro-inflammation. Major weaknesses in the current literature are the focus on degeneration without pain phenotyping, and lack of association of molecular findings with pain outcomes. PERSPECTIVE: This scoping review identified TNF-α, NF-κB signaling, and ROS-induced pro-inflammation as relevant mechanisms of human discogenic low back pain. Major weaknesses in the current literature are the focus on degeneration without pain phenotyping, and lack of association of molecular findings with pain outcomes. Keywords.

A rare presentation of segmental spinal dysgenesis: Clinical and radiological findings.

Segmental spinal dysgenesis is a rare and complex congenital condition affecting the dorso-lumbar spine, characterized by focal spinal cord dysgenesis and kypho-scoliotic deformity. It arises due to notochord malformation during embryogenesis. The case in question involves a 2-year-old female child. She presented to the outpatient department of our hospital with a history of inability to walk and increased frequency of micturition. The patient's mother had no antenatal visits. Upon examination, the patient was found to have a scoliotic deformity. Magnetic resonance imaging (MRI) of the spine revealed an absence of the spinal cord and spinal nerves from the T5 to L2 levels. A relatively thick spinal cord was visible from the L2 to L4 level. There was a complete absence of the spinal canal at the D10 and D11 levels, along with dorsal levoscoliosis. Segmental anomalies of the vertebrae were also noted in the dorsal spine. Additionally, imaging showed features of neurogenic bladder and mild left hydroureteronephrosis. The child underwent rehabilitation and surgical correction of the scoliosis.

Particularities of spasticity in myelomeningocele patients.

OBJECTIVE: Myelomeningocele (MMC), a congenital neural tube defect, is the most common developmental anomaly of the central nervous system (CNS). Spasticity is among the main disabling factors in these patients, affecting up to 1/5 of children. The purpose of this article is to review the current knowledge regarding spasticity in MMC patients, mainly focusing on its manifestations and management. METHODS: A literature search was conducted using the PubMed database for the terms "myelomeningocele" and "spasticity." Data were collected by 5 independent investigators and then synthesized in a scoping format. RESULTS: Causes of spasticity in these patients include hydrocephalus, tethered cord syndrome (TCS), syringomyelia, CNS infection, and associated congenital brain and spine anomalies. Clinical manifestations include limb spasticity and neurogenic bladder. Spasticity primarily affects muscles below the neurological level and contributes to gait impairment. Besides walking ability, spasticity also severely affects functional mobility in general, self-care, and quality of life. The majority of MMC patients experience neurogenic bladder. Treatment of spasticity can be symptomatic or target its cause. Medical and surgical options are available for both limb and bladder spasticity. Regular physiotherapy and orthotics are used to prevent contractures and the early introduction of orthoses is the cornerstone of a gait training program. Neurosurgical treatment options for spasticity include nonablative and ablative procedures such as selective dorsal rhizototmy. The urodynamic pattern guides treatment strategies, with intermittent catheterization being the best treatment option for patients with underactive detrusor and overactive sphincter muscles. CONCLUSION: Given the particularities of spasticity in MMC patients, a multidisciplinary team approach and early rehabilitation programs are keys for their optimal management.

Sacral neuromodulation for Organophosphate-induced delayed neuropathy neurogenic lower urinary tract dysfunction: a case report.

BACKGROUND: Organophosphate-Induced Delayed Neuropathy (OPIDN) is a rare neurological disorder triggered by exposure to organophosphorus compounds. These compounds exert their neurotoxic effects by impacting the nervous system, leading to systemic manifestations. Urinary system symptoms are infrequently observed in clinical settings. Currently, effective therapeutic interventions for OPIDN-related urinary symptoms are lacking. Sacral nerve modulation therapy, an FDA-approved approach for managing lower urinary tract symptoms, presents as a promising option. Herein, we present a case of OPIDN-induced lower urinary tract obstruction successfully treated with sacral nerve modulation therapy, resulting in substantial symptom relief. CASE REPORT: A 27-year-old male patient presented with severe bilateral hydronephrosis, attributed to low bladder compliance and accompanied by a fever persisting for 6 days. The patient's medical history revealed accidental ingestion of organophosphate pesticide (Dimethoate) with no concomitant underlying diseases. In consideration of the potential for OPIDN, surgical intervention in the form of sacral neuromodulation (phase I) was undertaken. Subsequent evaluation one month post-surgery revealed notable improvements in both bladder compliance and bilateral hydronephrosis, necessitating sacral neuromodulation (phase II). Presently, following a 5-month follow-up period, the patient remains asymptomatic and in favorable health. CONCLUSION: This patient achieved long-term relief using sacral neuromodulation.

TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models.

AIMS: Accumulating evidence indicates the involvement of TRESK potassium channels in migraine, however, effects of TRESK activation on migraine-related mechanisms remain unclear. We explored effects of TRESK channel modulation on migraine-related behavioral and molecular markers in in-vivo and ex-vivo rat models of migraine. MAIN METHODS: The selective TRESK activator cloxyquin at different doses, the TRESK inhibitor A2764, and the migraine drug sumatriptan were tested alone or in different combinations in nitroglycerin (NTG)-induced in-vivo model, and in ex-vivo meningeal, trigeminal ganglion and brainstem preparations in which CGRP release was induced by capsaicin. Mechanical allodynia, CGRP and c-fos levels in trigeminovascular structures and meningeal mast cells were evaluated. KEY FINDINGS: Cloxyquin attenuated NTG-induced mechanical allodynia, brainstem c-fos and CGRP levels, trigeminal ganglion CGRP levels and meningeal mast cell degranulation and number, in-vivo. It also diminished capsaicin-induced CGRP release from ex-vivo meningeal, trigeminal ganglion and brainstem preparations. Specific TRESK inhibitor A2764 abolished all effects of cloxyquin in in-vivo and ex-vivo. Combining cloxyquin and sumatriptan exerted a synergistic effect ex-vivo, but not in-vivo. SIGNIFICANCE: Our findings provide the experimental evidence for the anti-migraine effect of TRESK activation in migraine-like conditions. The modulation of TRESK channels may therefore be an attractive alternative strategy to relieve migraine pain.

Is body composition important in the context of renal function in pediatric neurogenic bladder?

BACKGROUND: Neurogenic bladder due to myelomeningocele (MMC) is a significant risk factor for chronic kidney disease in children. Cystatin C (CysC) is a more accurate GFR marker than creatinine as it is unaffected by muscle mass but may be influenced by fat mass and BMI. This study evaluates: (1) GFR measurement accuracy using CysC and creatinine in MMC-related neurogenic bladder, (2) the relationship between body composition via bioelectrical impedance analysis (BIA) and renal parameters, and (3) the use of BIA for non-invasive GFR and body composition assessment. METHODS: Forty children (median age 9.96 years) underwent serum creatinine, CysC testing, and BIA measurements. We assessed age, sex, spinal lesion level, anthropometric measurements, BMI, and activity using Hoffer's scale. GFR was calculated using five creatinine-based formulas, three CysC-based, and three combining CysC and creatinine, including BIA GFR as an alternative approach. RESULTS: Creatinine-based GFR estimates were significantly higher than CysC-based GFR. Although only 30% of MMC patients met the traditional BMI criteria for overweight/obesity, 62.5% were obese based on BIA-measured body fat percentage. Significant differences were found in CysC and CysC-based GFR equations within BMI and fat mass groups. Positive correlations were observed between CysC and body weight, BMI percentiles, body fat mass and fat-to-muscle ratio. Muscle mass positively correlated with creatinine. CONCLUSIONS: BIA-determined fat mass percentage is a more sensitive obesity indicator than BMI in MMC patients. CysC levels and CysC-based GFR equations are influenced by body fat mass, requiring consideration of adiposity to avoid misestimating renal impairment.

Cross-cultural adaptation and psychometric properties of the Chinese version of the Intermittent Self-Catheterization Questionnaire (ISC-Q).

Background: The intermittent self-catheterization questionnaire (ISC-Q) is a valid and reliable tool to assess the quality of life (QOL) in patients with neurogenic lower urinary tract dysfunction (NLUTD) who engage in ISC. The aim of this research is to culturally adapt the ISC-Q and evaluate its psychometric properties within the Chinese patient population. Methods: The cross-sectional research was meticulously conducted in two pivotal stages: initially, the focus was on cross-cultural adaptation, followed by an extensive phase of psychometric testing. This comprehensive analysis involved 405 Chinese patients with NLUTD who use ISC. Various analyses, including evaluations of the floor and ceiling effects, item analysis, content validity, exploratory and confirmatory factor analysis (EFA and CFA), assessments of convergent, discriminant, and criterion validity. Additionally, Cronbach's alpha was utilized to determine internal consistency, and test-retest reliability was measured using the intraclass correlation coefficient (ICC). Results: No floor and ceiling effects were observed. The content validity index was 0.967. The EFA identified four factors, accounting for 64.953% of the total variance, and this four-factor structure was confirmed by the CFA. The fit indices in CFA were favorable, with χ2/df = 1.999, root mean square error of approximation = 0.070, comparative fit index = 0.916, Tucker-Lewis index = 0.900, goodness-of-fit index = 0.863, and incremental fit index = 0.917. The average variance extracted for the four factors ranged from 0.466 to 0.565, with composite reliability values ranging from 0.776 to 0.859. The ISC-Q showed a positive correlation with the intermittent self-catheterization acceptance questionnaire (r = 0.557, P < 0.001). The ICC overall Cronbach's alpha coefficient for the questionnaire was 0.821, and the for test-retest reliability was 0.951 (95% CI [0.900-0.976] P < 0.001). Conclusion: The validity and reliability of the Chinese version of the ISC-Q have been verified, making it suitable for measuring the QOL in NLUTD patients who practice ISC.

Brain lesion and echocardiogenic predictors of newly detected atrial fibrillation in acute ischemic stroke.

OBJECTIVES: Atrial fibrillation (AF) is one of the notorious risk factors in acute ischemic stroke (AIS), and the use of anticoagulants has been shown to be effective in preventing ischemic stroke in AF patients. Therefore, identifying AF in AIS patients has become increasingly important. However, the impact of brain imaging and cardiac indices on the development of new AF after stroke remains unclear. METHODS: A consecutive series of AIS patients who were admitted to the Ulsan University Hospital between January 2013 and December 2019 were identified. Patients with relevant ischemic brain lesions on MRI were included, and those without echocardiography data were excluded. We included and classified the AF patients who had the disease prior to or during hospitalization or met the criteria for cryptogenic stroke (CS). Differences in baseline characteristics, stroke risk factors, stroke severity, insular lesion, and echocardiographic data were investigated among each group. RESULTS: A total of 850 patients were enrolled in the study, comprising 231 patients with AF detected after stroke (AFDAS), 287 patients with known AF (KAF), and 350 patients with CS. Compared with KAF, patients with AFDAS had a lower prevalence of underlying coronary heart disease and stroke history. They had greater right insular cortex lesions and lesser left atrial enlargement in unadjusted analysis. Following adjusted analysis, the involvement of the right insular cortex was found to be associated with the AFDAS patient group (odds ratio, 1.57). When compared to the CS group, AFDAS patients were older, experienced more severe initial strokes, and had similar rates of pre-stroke anticoagulation prescription. Additionally, they demonstrated a higher prevalence of both insular lesions, increased left atrium volume index, reduced ejection fraction, and elevated e/e' ratio. After adjustment, age, initial stroke severity, insular involvement, left atrium volume index, ejection fraction, and e/e' ratio were found to be significant. CONCLUSIONS: These results suggest that the right insular cortex lesion on acute stroke may be a cause of AFDAS.

Does Surgical Treatment for Benign Prostate Enlargement (BPE)-Related Bladder Outlet Obstruction (BOO) Benefit Patients with Central Nervous System Diseases? A Systematic Review.

Background/Objectives: Bladder outlet obstruction (BOO) resulting from benign prostate enlargement (BPE) is a common cause of lower urinary tract symptoms (LUTS) in men. Patients with central nervous system (CNS) diseases, such as spinal cord injury (SCI), Parkinson's disease (PD), cerebrovascular accident (CVA) and multiple systemic atrophy (MSA), commonly experience lower urinary tract dysfunction. Men who suffer from CNS diseases may also experience symptoms related to BPE and BOO, which pose an additional burden to their overall clinical status and result in the need for catheter use and a deterioration in quality of life. The aim of this study was to identify if prostate surgery will benefit men with CNS diseases who have been diagnosed with BPE-related BOO. Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. EMBASE, MEDLINE, Cochrane systematic reviews, Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov were searched from 1946 up to July 2023 for peer-reviewed publications addressing the primary outcome (success rate) and the secondary outcomes (postoperative changes in incontinence episodes, urodynamic parameters, questionnaire scores, and quality of life). In addition, the perioperative outcomes (adverse events and the need for further medical or surgical therapy) were reported. Results: A total of 1572 abstracts were screened, and 13 studies involving 1144 patients were eligible for inclusion. Six studies assessed the effect of prostate surgery for BPE-related BOO in SCI, four studies in CVA, two studies in PD, and one study in the MSA population. All studies were considered to have a high risk of bias. Transurethral resection of the prostate (TURP) was the most common de-obstruction procedure, followed by prostatic artery embolism and open prostatectomy. The overall pooled success rate was calculated as 81.4% (65-100%) in SCI, 27.1% (9-70%) in PD, and 66.7% (50-79%) in CVA populations. The risk of de novo incontinence was 24.7-50% in SCI, 20% in PD, 21-50% in CVA, and 60% in MSA population. In patients with SCI with BPE-related BOO, prostate surgery improved mean bladder compliance and detrusor filling pressure and resolved detrusor overactivity in up to 50% of patients. Improvement of free flow rate, voided volume, and post-void residual was observed in all patients. Patients with CVA had an increased risk of perioperative mortality compared to non-CVA patients, and the risk of postoperative complications was inversely proportional to the timing of the CVA insult since surgery. Conclusions: This systematic review provides an overview of the available evidence on the outcome of prostate surgery in patients with neurologic diseases and BPE-related BOO. Identifying the optimal practice was challenging due to the limited availability of high-quality studies and the high variability of the reported outcomes. Properly selected patients with neurological diseases may benefit from prostate surgery, provided that preoperative investigations indicate BPE-related BOO.

"I'm a bathroom expert": a qualitative study exploring how students with physical disabilities manage toileting during college.

Introduction: Health care providers caring for youth with physical disabilities encourage them to be as independent as possible, which includes obtaining higher education when feasible. However, little is known about the experiences of higher education students in managing their toileting. Methods: We performed 1:1 semi-structured interviews with 13 current college students with physical disabilities (4 male, 9 female), of whom six were on a formal bladder and/or bowel management program. Three researchers analyzed all transcripts using constructivist grounded theory procedures. Results: We identified six themes, including: (1) adherence to prescribed programs, (2) importance of time management, (3) interfering with class, (4) balancing intake and toileting, (5) campus bathroom experiences, and (6) acclimating to new living situations. Students needed strong personal skills in time management, adaptability, and self-advocacy to both manage their toileting needs and engage in academic and social activities. This often took time to develop while in college. They faced barriers such as a lack of private, well-maintained bathrooms. Conclusions: Health care providers should encourage their patients to develop these personal skills prior to starting college, while colleges need to better support these students through honoring their accommodation needs and ensuring the availability of private, accessible bathrooms.

Intrathecal baclofen obviating the need for bladder stimulator use in a patient with secondary dystonia: illustrative case.

BACKGROUND: Children with cerebral palsy often have neurogenic bladders. Bladder function is further affected by complex medical management and multifactorial disease processes, leading to worsened function and poorer quality of life. Intrathecal baclofen (ITB) therapy has been used to treat hypertonia and spasticity, but implications in neurogenic bladder management have not been well described. OBSERVATIONS: A 20-year-old female with a history of cerebral palsy and neurogenic bladder treated with sacral neuromodulation underwent ITB therapy and subsequently experienced improvement in bladder control, obviating the need for bladder stimulator use. LESSONS: ITB improves hypertonia and can effectively obviate the need for neurostimulation to treat neurogenic bladder in patients with cerebral palsy. Further research is necessary to discern mechanisms. https://thejns.org/doi/10.3171/CASE24364.

[Professor YANG Jun's experience in treatment of neuropathic tinnitus with acupuncture and moxibustion based on disease elements].

Based on Chinese medicine classics, combined with clinical experience and modern research findings, Professor YANG Jun deepens the analysis on the etiology and pathogenesis of neuropathic tinnitus, and has summarized the TCM elements of this disease, including "qi and blood stagnation" and "shen (spirit) hidden and orifices closed". The multiple therapies are used in combination, such as acupuncture, electroacupuncture, warm needling, borneol-moxibustion and herbal medication. The different acupoints are combined according to individuals, especially the application of Tinggong (SI 19) and Yamen (GV 15). The comprehensive treatment overlaps the dose effects, co-acts on activating blood circulation in meridians, calming-down the spirit and opening the orifices so that the therapeutic effect of acupuncture and moxibustion can be improved on this disease.

Impact of urinary catheters including reusable catheters on quality of life and work productivity in persons with spinal cord lesion.

While preventing renal damage and symptomatic urinary tract infection are of paramount importance to persons with a spinal cord lesion (SCL), patient-reported outcomes (PROs) are receiving much more attention than ever before. We performed a cross-sectional internet survey of 282 adult members of SCL patient advocacy groups and investigated, for the first time, the impact of different types of urinary catheter, including a Japanese reusable silicone catheter and a reusable intermittent balloon catheter, on PROs of persons with SCL. Intermittent self-catheterization (ISC) did not surpass continuous indwelling catheterization in terms of a disease-specific urinary quality of life. Urinary incontinence, regular ISC, and performing ISC away from home confronted these individuals. Work productivity and regular activities correlated fairly well with the disease-specific urinary quality of life. Bowel management problems affected all PROs evaluated. The absence of differences in PROs among the types of catheter used for ISC implies that Japanese reusable catheters have the potential to benefit selected persons with SCL. Further research is warranted to develop measures for maximizing work productivity by overcoming urinary as well as bowel problems.

Novel Diagnosis and Treatment for Neurogenic Thoracic Outlet Syndrome.

This article presents a unique diagnostic test for the neurogenic thoracic outlet syndrome (nTOS). nTOS is one of the most misdiagnosed and controversial medical problems; the diagnosis is clinical, and there are few specific diagnostic criteria for this condition. We would like to share this unique diagnostic modality, the Tafler test, with medical professionals. The Tafler test helps diagnose nTOS, differentiate it from cervical radiculopathy and carpal tunnel syndrome, and effectively tailor treatment for its symptoms. The following case series aims to describe several patients with nTOS who had failed previous treatment with surgery, physical therapy, and analgesics. The implementation of the Tafler test as a treatment modality in combination with osteopathic manipulative treatment (OMT) and physical therapeutic modalities led to significant improvements in treatment efficiency.

Modulating oxidative stress and neurogenic inflammation: the role of topiramate in migraine treatment.

Migraine is a chronic, recurrent neurovascular disorder characterized by episodes closely associated with neurovascular hypersensitivity. Oxidative stress can worsen the hypersensitive state of the central nervous system, which in turn can trigger pro-inflammatory factors that result in neurogenic inflammation. Topiramate is frequently used as a preventative measure for migraines, but there is currently little empirical data to support its efficacy through pathways related to neurogenic inflammation and oxidative stress. This review provides an overview of current knowledge regarding the etiology, inducements, pathophysiology, and available treatments for migraine, with a focus on the clinical and experimental evidence of neurogenic inflammation and oxidative stress in migraine. It also delves into the antioxidant and anti-inflammatory qualities of topiramate, clarifying the possible ways in which topiramate affects these pathways to lessen migraine symptoms.

Interplay between cannabinoids and the neuroimmune system in migraine.

Migraine is a common and complex neurological disorder that has a high impact on quality of life. Recent advances with drugs that target the neuropeptide calcitonin gene-related peptide (CGRP) have helped, but treatment options remain insufficient. CGRP is released from trigeminal sensory fibers and contributes to peripheral sensitization, perhaps in part due to actions on immune cells in the trigeminovascular system. In this review, we will discuss the potential of cannabinoid targeting of immune cells as an innovative therapeutic target for migraine treatment. We will cover endogenous endocannabinoids, plant-derived phytocannabinoids and synthetically derived cannabinoids. The focus will be on six types of immune cells known to express multiple cannabinoid receptors: macrophages, monocytes, mast cells, dendritic cells, B cells, and T cells. These cells also contain receptors for CGRP and as such, cannabinoids might potentially modulate the efficacy of current CGRP-targeting drugs. Unfortunately, to date most studies on cannabinoids and immune cells have relied on cell cultures and only a single preclinical study has tested cannabinoid actions on immune cells in a migraine model. Encouragingly, in that study a synthetically created stable chiral analog of an endocannabinoid reduced meningeal mast cell degranulation. Likewise, clinical trials evaluating the safety and efficacy of cannabinoid-based therapies for migraine patients have been limited but are encouraging. Thus, the field is at its infancy and there are significant gaps in our understanding of the impact of cannabinoids on immune cells in migraine. Future research exploring the interactions between cannabinoids and immune cells could lead to more targeted and effective migraine treatments.

Pathology and physiology of acid-sensitive ion channels in the bladder.

Acid-sensitive ion channels (ASICs) are sodium-permeable channels activated by extracellular acidification. They can be activated and trigger the inward flow of Na+ when the extracellular environment is acidic, leading to membrane depolarization and thus inducing action potentials in neurons. There are four ASIC genes in mammals (ASIC1-4). ASIC is widely expressed in humans. It is closely associated with pain, neurological disorders, multiple sclerosis, epilepsy, migraines, and many other disorders. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a specific syndrome characterized by bladder pain. Recent studies have shown that ASICs are closely associated with the development of BPS/IC. A study revealed that ASIC levels are significantly elevated in a BPS/IC model. Additionally, researchers have reported differential changes in ASICs in the bladders of patients with neurogenic lower urinary tract dysfunction (NLUTD) caused by spinal cord injury (SCI). In this review, we summarize the structure and physiological functions of ASICs and focus on the mechanisms by which ASICs mediate bladder disease.