Sensory Abnormalities Research Articles

Morphological aberration of corneal nerves in hyposecretory dry eye guinea pigs.

Dry eye, a common ocular surface disease associated with tear film instability and corneal impairment, is frequently accompanied by ocular discomfort and pain. Recent research has shown that corneal nerve dysfunction may play a role in certain pathologies of dry eye; however, the details remain unclear. To clarify the aberration in corneal nerves underlying sensory abnormalities, in addition to corneal impairment in dry eye, we examined the morphological alterations of nerve fibers in the corneas excised from guinea pigs with dry eye, where the lacrimal glands were surgically excised. Guinea pigs with dry eye exhibited reduced tear volume, increased spontaneous blink frequency, and corneal epithelial damage. Simultaneously, the subbasal nerve plexus in the cornea visualized using an anti-tubulin βIII antibody partially outgrew and became convoluted. The morphology of peptidergic nerves containing calcitonin gene-related peptide, which may function as a polymodal nociceptor, was also altered. These results indicate that guinea pigs with excised lacrimal glands can serve as useful tools for investigating the neuronal mechanisms underlying corneal pathology in dry eyes. Additionally, chronic tear deficiency may considerably alter nerve structure, including peptidergic nerves in the cornea, accompanied by epithelial damage and increased blink frequency.

Exploring non-canonical targets in Alzheimer’s disease: a departure from the norm

AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, and cognitive decline. Despite advances in understanding AD pathophysiology and the expansion of therapeutic options over the past three decades, the disease remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring the need for innovative treatment approaches beyond symptomatic relief. This calls for a re-examination of AD pathology to identify potential therapeutic targets that go beyond conventional strategies. This review highlights four of the most promising non-canonical therapeutic targets: oligodendrocytes, the blood–brain barrier (BBB), neuroimmunometabolism, and the coagulation system. These components are crucial for maintaining the integrity and proper function of neurons and the brain, playing key roles in the progression of AD. Oligodendrocytes, for example, are essential for myelination and neuronal support, while BBB dysfunction can lead to impaired clearance of toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses in the brain and dysregulation of the coagulation system has been linked to increased neuroinflammation and vascular abnormalities in AD. Recent discoveries in these fields provide new avenues for understanding the disease and identifying potential therapeutic targets. By exploring these non-canonical pathways, future research may offer breakthroughs in treating AD, moving beyond symptomatic management towards disease-modifying strategies.

Magnetoencephalography studies in migraine and headache disorders: A systematic review.

Understanding the neural mechanisms underlying migraine and other primary headache disorders is critical for the development of long-term cures. Magnetoencephalography (MEG), an imaging modality that measures neuronal currents and cortical excitability with high temporal and superior spatial resolution, has been increasingly used in neurological research. Initial MEG studies showed promise in directly recording cortical spreading depression-a cortical correlate of migraine with aura. However, lately MEG technology has highly evolved with greater potential to reveal underlying pathophysiology of migraine and primary headache disorders, and aid in the identification of biomarkers. To systematically review the use of MEG in migraine and other primary headache disorders and summarize findings. We conducted a systematic search and selection of MEG studies in migraine and primary headache disorders from inception until June 8, 2023, in Medline, Embase, Cochrane, and Scopus databases. Peer-reviewed English articles reporting the use of MEG for clinical or research purposes in migraine and primary headache disorders were selected. We found 560 articles and included 38 in this review after screening. Twelve studies investigated resting-state, while others investigated a sensory modality using an evoked or event-related paradigm with a total of 35 cohort and 3 case studies. Thirty-two studies focused exclusively on migraine, while the rest reported other primary headache disorders. The findings show an evolution of MEG from a 7- to a 306-channel system and analysis evolving from sensor-level evoked responses to more advanced source-level connectivity measures. A relatively few MEG studies portrayed migraine and primary headache disorders as a sensory abnormality, especially of the visual system. We found heterogeneity in the datasets, data reporting standards (due to constantly evolving MEG technology and analysis methods), and patient characteristics. Studies were inadequately powered and there was no evidence of blinding procedures to avoid selection bias in case-control studies, which could have led to false-positive findings. More studies are needed to investigate the affective-cognitive aspects that exacerbate pain and disability in migraine and primary headache disorders.

The Association Between Urinary Incontinence With Pelvic Pain and Sensory-Motor Function in Older Women With Stroke.

The study aimed to investigate the association between urinary incontinence (UI) severity, pelvic pain, and sensory-motor function in older women with stroke. A cross-sectional prospective study was carried out with 102 older women individuals with stroke. Barthel Index (BI), Incontinence Impact Questionnaire Short Form (IIQ-7), Urogenital Distress Inventory (UDI-6), Pelvic Pain Impact Questionnaire (PPIQ), Somatosensory Amplification Scale (SASS), and Somatic Sensitivity Scale (SeSS) were used for clinical measurements. Partial correlational analyses with age, stroke duration, and BMI as covariates revealed a moderate positive correlation between SASS and IIQ-7 (r = 0.315, p < 0.001) and UDI-6 (r = 0.376, p < 0.001). On the other hand, there was a strong positive correlation between SASS and PPIQ (r = 0.522, p < 0.001). SeSS had a low positive correlation with IIQ-7 (r = 0.198, p < 0.05) and UDI-6 (r = 0.203, p < 0.05). In addition, there was a positive and moderate correlation between SeSS and PPIQ (r = 0.384, p < 0.001). Multivariate linear regression analysis revealed causality of SASS (R2 = 0.381, p < 0.001) and SeSS (R2 = 0.167, p < 0.001) with PPIQ. Increased abnormal sensory sensitivity is associated with increased pelvic pain levels in women with stroke. Clinicians should consider sensory abnormalities, especially pain, within the scope of UI in women with stroke. Our results provide preliminary essential data for sensory and pain awareness during pelvic rehabilitation in stroke patients.

Small Fiber Neuropathy in Burning Mouth Syndrome: A Systematic Review.

Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder, characterized by persistent burning sensations and pain without clear pathological causes. Recent research suggests that small fiber neuropathy (SFN) may play a significant role in the neuropathic pain and sensory disturbances associated with BMS. Following PRISMA guidelines, this systematic review aims to evaluate and synthesize current evidence supporting SFN's involvement in BMS. The protocol is registered in PROSPERO (CRD42024555839). The results show eight studies reported reductions in nerve fiber density in tongue biopsies (ranging from 30% to 60%), along with morphological changes indicative of small fiber damage. Additionally, an increase in TRPV1-positive, NGF-positive, and P2X3-positive fibers, overexpression of Nav1.7, and slight underexpression of Nav1.9 mRNA were observed in BMS patients. Quantitative Sensory Testing in seven studies revealed sensory abnormalities such as reduced cool detection and cold pain thresholds. Blink reflex and corneal confocal microscopy also indicated peripheral and central small fiber damage, along with increased artemin mRNA expression. The evidence strongly supports SFN as a key factor in the pathophysiology of BMS, particularly due to reductions in nerve fiber density and altered sensory thresholds. However, variability across studies highlights the need for larger, standardized research to establish causal relationships and guide therapeutic strategies.

A longitudinal study on the development trajectory of auditory processing and its relationship with language development in Chinese preschool children with autism spectrum disorder: study protocol

BackgroundIt was reported that more than 96% of autism spectrum disorder (ASD) children are accompanied with different degrees of sensory processing abnormalities, and up to 50% of ASD children exhibit abnormal auditory response. Studies have confirmed that some ASD children’s abnormal auditory response may be related to their abnormal auditory processing. Prior research demonstrated that ASD children’s auditory processing has high heterogeneity, thus, ASD children’s auditory processing may have different developmental trajectories. However, no study has concentrated on the developmental trajectories of ASD children’s auditory processing. In addition, auditory processing plays a crucial role in ASD children’s language development, thus, ASD children’s different language development outcomes may be related to different auditory processing development tracks. Therefore, this study aims to explore the developmental trajectory of auditory processing in ASD children and analyze the relationship between different developmental trajectories of auditory processing and language impairment.Methods/DesignIn this study, 220 ASD children aging 3 years and 0 months to 4 years and 11 months are recruited as the research objects, and their demographic characteristics are collected. The subjects are tested for peripheral hearing, intelligence, and autism symptoms. Furthermore, ASD children’s auditory processing and language development are evaluated at baseline, 1 year, and 2 years later. In addition, ASD children’s auditory processing is evaluated by electrophysiological test and the Preschool Auditory Processing Assessment Scale. Moreover, ASD children’s language skills are assessed using the Language Development Assessment Scale for Children Aged 1–6. The various categories of the developmental trajectory of ASD children’s auditory processing are examined through the latent category growth model. Additionally, a hierarchical regression model is developed to analyze the predictive impact of different auditory processing development trajectories on language impairment in ASD children.DiscussionThis longitudinal study will explore the categories of auditory processing developmental trajectories in ASD children, and analyze the relationship between different categories of auditory processing developmental trajectories and language development, providing new ideas and targeted targets for the rehabilitation training of language impairment in ASD children, as well as promoting early and accurate interventions for ASD children.

From Compression to Itch: Exploring the Link Between Nerve Compression and Neuropathic Pruritus.

Neuropathic itch is a type of chronic pruritus resulting from neural dysfunction along the afferent pathway. It is often accompanied by abnormal sensations such as paresthesia, hyperesthesia, or hypoesthesia. This condition, which may involve motor or autonomic neural damage, significantly impacts patients' quality of life, causing severe itch and associated comorbidities such as depression, disrupted sleep, and social strain. Neuropathic itch accounts for 8% of chronic pruritus cases, though this may be underestimated. This comprehensive review focuses on nerve impingement as the primary pathophysiological mechanism for various forms of neuropathic itch including brachioradial pruritus (BRP), notalgia paresthetica (NP), and anogenital itch. BRP, often seen in middle-aged white women, manifests as pruritus in the dorsolateral forearms typically exacerbated by ultraviolet (UV) exposure and related to cervical spine pathology. NP, prevalent in middle-aged women, presents as pruritus in the upper back due to thoracic spine nerve compression. Anogenital pruritus, affecting 1-5% of adults, is often linked to lumbosacral spine issues after ruling out dermatologic conditions such as lichen sclerosus or lichen simplex chronicus. The pathophysiology of neuropathic itch involves both peripheral and central mechanisms, with nerve damage being a key factor. Diagnosis requires a thorough history, physical examination, and potentially imaging studies. Topical agents such as menthol, capsaicin, and lidocaine are used for mild cases, while systemic medications such as gabapentin, pregabalin, and antidepressants are prescribed for moderate to severe cases; however, no USFood and Drug Administration (FDA)-approved therapies currently exist specifically for neuropathic itch. Understanding the underlying neural dysfunction and appropriate therapeutic strategies is crucial for managing neuropathic itch effectively.

Impact of medical adhesives on persistent fluid extravasation at needle injection sites in patients with severe edema: a randomized controlled trial.

To investigate the efficacy of medical glue in halting fluid extravasation at needle insertion sites in patients with severe edema. Sixty patients with severe edema were recruited between June 2022 and June 2023 and randomly allocated into either the control group or the experimental group, with 30 cases in each. In the experimental group, after intramuscular injection, medical glue was administered at the needle insertion site, and covered with gauze dressing upon curing, and subsequently subjected to pressure bandaging. Patients were instructed to limit their activity. Meanwhile, the control group received conventional nursing procedures involving pressure bandaging and activity restriction. The effectiveness of nursing interventions in halting exudation, duration of hospitalization, duration of exudation, nursing expenses, skin complications (infection, rash, abrasion, abnormal sensation, etc.), and patient satisfaction with nursing care were monitored. Comparison between the two groups revealed statistically significant differences in several aspects: the success rate of halting exudation, duration of exudation, total skin complication rate, and overall satisfaction [83.3% vs. 20.0%, (2.20 ± 2.76) days vs. (7.33 ± 3.28) days, 6.67% vs. 33.33%, 80.00% vs. 36.67%, P < 0.05]. However, there were no statistically significant differences in hospitalization time and nursing expenses [(14.50 ± 5.17) days vs. (14.00 ± 3.95) days, (537.53 ± 264.19) yuan vs. (661.97 ± 305.55) yuan, P > 0.05]. Medical glue demonstrates effectiveness in halting fluid extravasation at needle insertion sites among patients experiencing severe edema. Additionally, it reduces the duration of exudation, diminishes skin complications resulting from exudation, and significantly enhances patient satisfaction with nursing care. Given these benefits, its clinical adoption and application are highly recommended.

A Retrospective Study of Lateral Antebrachial Cutaneous Nerve Neuropathy: Electrodiagnostic Findings and Etiologies in 49 Cases.

The lateral antebrachial cutaneous nerve (LACN) is the terminal sensory branch of the musculocutaneous nerve and is rarely entrapped or injured. This study describes the electrodiagnostic (EDX) findings and etiologies of LACN neuropathy. This is a review of 49 patients with pain and/or paresthesia of the forearm who underwent EDX studies. The diagnosis of LACN neuropathy was based on clinical and sensory conduction abnormalities. The most common etiology of LACN neuropathy was iatrogenic injury in 30 (61.2%) patients, primarily due to biceps tendon repair at the elbow (11 [36.7%]) and phlebotomy (5 [16.7%]). Fifteen (30.6%) patients sustained a non-iatrogenic injury at the proximal forearm/elbow, consisting of six (60%) laceration injuries and five (33.3%) stretch injuries. Four (8.2%) patients comprised the "other" etiology category, including two mass lesions causing LACN compression. Pain, paresthesia, and/or numbness in the LACN distribution were reported in 33 (67.3%), 27 (55.1%), and 23 (46.9%) patients, respectively. Hypoesthesia was detected in 45 (91.8%) patients, and dysesthesia in 7 (14.3%). The sensory nerve action potentials (SNAPs) of the LACN on the symptomatic side were absent in 44 (89.8%) patients. Of the five patients whose SNAPs of the LACN were detected, all had a decreased amplitude, and two had increased sensory latency. The most common etiology for LACN neuropathy in this series was iatrogenic injury; repair of biceps tendon at the elbow was the most frequent provoking cause. Protection of the LACN during surgical procedures at the elbow and forearm is vital to prevent iatrogenic injury.

6610 Emphasizing the evaluation of autonomic dysfunctioncontributes to the diagnosis of ROHHAD Syndrome -- Based on a comparative analysis of two center ROHHAD Syndrome case reports and reported literature

Abstract Disclosure: Y. Wang: None. L. Chen: None. C. Gong: None. Background: ROHHAD is the acronym of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysfunction, it is an extremely rare and potentially fatal disease.The purpose of this study is to describe the clinical symptoms and timelines of ROHHAD syndrome. Methods: All patients with ROHHAD syndrome were included. Patients from 2007 to2019 published previously was regarded as group 1. We searched for the keyword "ROHHAD" in the PUMBED database, and included all literature describing theclinical symptoms of ROHHAD patients (group 2, from October 2019 to August 2023).We compared and analyzed the above two sets of data with our data (group 3). Results: In the past 2 years, we diagnosed 16 cases of ROHHAD syndrome totally, with a male to female ratio of 8:8. Mean BMI z score was 4.23 ± 1.70, and the age of rapid obesity was 3.17 (1.67, 7.92) years old, ranging from 3 to 22.5 kg/year. The age at which hypoventilation, hypothalamic dysfunction, and autonomic dysfunction occurred was 5.55 (3.61, 8.25) years old, 4.46 (1.83, 9.25) years old, 3.42 (1.83, 8.00) years old, respectively. The most common autonomic dysfunction were cardiovascular manifestations (13 cases), thermal dysregulation and excessive sweating (each with 11 cases). Totally 13 cases had emotional, cognitive and behavioral abnormalities, 7 cases had neurogenic tumors. Case 2 had neurogenic tumors more than 5 years before rapid obesity, cognitive and behavioral abnormalities more than 2 years ago. Case 10 had abnormal pain sensation shortly after birth, and following polyuria in 2 years before rapid obesity. A total of 116 patients including 100 cases previously reported and 16 cases in this study were analyzed. Compared with the incidence rates of rapid obesity, central hypoventilation and hypothalamic dysfunction in patients in this study, there was no statistically significant difference between three groups. Among patients who had autonomic dysfunction (group 1 vs group 2 vs group 3), thermal dysregulation was 65.7% vs 17.0% vs 68.8%, cardiovascular manifestations was NA vs 12.8% vs 81.2%, excessive sweating was 28.6% vs 10.6% vs 68.8%, gastrointestinal disturbances was 11.4% vs 8.5% vs 62.5%, strabismus was 25.7% vs 12.8% vs 62.5%, and sleep disturbance was NA vs 6.4% vs 50.0%, all p&amp;lt; 0.05. The incidence of abnormal emotion, cognition and behavior was NA vs 29.8% vs 81.2% (p&amp;lt;0.05). Conclusion: The incidence of autonomic dysfunction in 16 patients of this study is100%, with multiple manifestations of autonomic dysfunction coexisting. The incidenceof autonomic dysfunction and abnormal emotion, cognition and behavior in reportedcases from different eras were significantly lower than those of our study, indicating theimportance of fully evaluating the autonomic dysfunction and limbic system. Fewpatients may occur tumors or autonomic dysfunction before rapid obesity. Presentation: 6/3/2024

B-301 Deciphering Neuropathy features in the Context of Nitrous Oxide abuse: An Integrated Analysis of Electrophysiology and Metabolism

Abstract Background Nitrous oxide (N2O), used medically for its analgesic and anxiolytic properties, has emerged as a common recreational substance, leading to a rise in chronic toxicity cases. N2O abuse induces peripheral neurological damage with a spectrum of clinical presentations, ranging from mild sensory disturbances to severe motor deficits. Neurological complications from N2O include axonal and demyelinating neuropathies, leading to diagnostic and prognostic challenges. The pathophysiology of N2O toxicity is linked to functional inactivation of vitamin B12, resulting in biochemical and electrophysiological alterations. This study aims to enhance understanding of N2O pathophysiology by examining metabolic changes in consumers with axonal and demyelinating patterns. Methods This study included 35 patients with recent N2O abuse (last declarative consumption within the past week) who were treated at Lille University Hospital between March 2020 and April 2023 and underwent electromyography. The collected clinical features encompassed sensory symptoms, motor weakness, gait abnormalities and deep tendon reflexes. Patients were classified based on clinical phenotypes, distinguishing between length-dependent and non-length dependent, sensory or sensory-motor involvement and their peripheral neuropathy disability (PND) score (ranging from I to IV). Neurophysiological data analysis followed the criteria of Hadden et al. to identify patients with demyelinating criteria, while those lacking demyelinating criteria were categorized as “axonal” in the neuropathy group. Simultaneously, biochemical evaluations of serum vitamin B12 and B9 by CLIA methods (Roche), along with plasma homocysteine by LC/MS/MS and CLIA methods (Snibe), methylmalonic acid (MMA), and methionine by LC/MS/MS, were systematically performed for all patients. Results 40% of the selected patients exhibited demyelination criteria. The demyelinated group showed a significantly higher disability PND score compared to the axonal group (3.0 and 2.2, respectively; p-value = 0.028). Elevated levels of homocysteine and methylmalonic acid were found in all patients. Interestingly, plasma concentrations of homocysteine were significantly higher in the group of patient with axonal outcomes compared to the demyelinating group (90 µM and 114 µM; p-value = 0.04), suggesting an involvement of homocysteine in the type of lesion related to N2O abuse. Conclusions This study highlights the diverse electrophysiological manifestations of N2O-induced neuropathy and highlight the potential role of metabolic parameters as biomarkers to understand the pathophysiology. Indeed, lower hyperhomocysteinemia levels were observed in demyelinating patterns, highlighting a potentially biochemical difference between the groups: plasma homocysteine could also be used as a marker of neurological severity. The homocysteine assay used in these conditions must enable the patient to be managed rapidly: it would therefore be preferable to use rapid methods such as immunoanalysis. On the other hand, plasma methylmalonic acid did not differ between groups, which also suggests that other mechanisms have yet to be identified in the pathophysiology of N2O abuse.

Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance.

The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology. We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS). Ten predictors, such as "vitality," "immunomodulating drugs," sensory symptoms," and "ethnicity," remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13). Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.

Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA

BackgroundA spinal cord injury (SCI) can result in severe impairment and fatality as well as significant motor and sensory abnormalities. Exosomes produced from IPSCs have demonstrated therapeutic promise for accelerating spinal cord injury recovery, according to a recent study.ObjectiveThis study aims to develop engineered IPSCs-derived exosomes (iPSCs-Exo) capable of targeting and supporting neurons, and to assess their therapeutic potential in accelerating recovery from spinal cord injury (SCI).MethodsiPSCs-Exo were characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. To enhance neuronal targeting, iPSCs-Exo were bioengineered, and their uptake by neurons was visualized using PKH26 labeling and fluorescence microscopy. In vitro, the anti-inflammatory effects of miRNA-loaded engineered iPSCs-Exo were evaluated by exposing neurons to LPS and IFN-γ. In vivo, biodistribution of engineered iPSC-Exo was monitored using a vivo imaging system. The therapeutic efficacy of miRNA-loaded engineered iPSC-Exo in a SCI mouse model was assessed by Basso Mouse Scale (BMS) scores, H&E, and Luxol Fast Blue (LFB) staining.ResultsThe results showed that engineered iPSC-Exo loaded with miRNA promoted the spinal cord injure recovery. Thorough safety assessments using H&E staining on major organs revealed no evidence of systemic toxicity, with normal organ histology and biochemistry profiles following engineered iPSC-Exo administration.ConclusionThese results suggest that modified iPSC-derived exosomes loaded with miRNA have great potential as a cutting-edge therapeutic approach to improve spinal cord injury recovery. The observed negligible systemic toxicity further underscores their potential safety and efficacy in clinical applications.

A survey of detection of Parkinson’s disease using artificial intelligence models with multiple modalities and various data preprocessing techniques

Parkinson’s disease (PD) is a neurodegenerative brain disorder that causes symptoms such as tremors, sleeplessness, behavioral problems, sensory abnormalities, and impaired mobility, according to the World Health Organization (WHO). Artificial intelligence, machine learning (ML), and deep learning (DL) have been used in recent studies (2015–2023) to improve PD diagnosis by categorizing patients and healthy controls based on similar clinical presentations. This study investigates several datasets, modalities, and data preprocessing techniques from the collected data. Issues are also addressed, with suggestions for future PD research involving subgrouping and connection analysis using magnetic resonance imaging (MRI), dopamine transporter scan (DaTscan), and single-photon emission computed tomography (SPECT) data. We have used different models like Convolutional Neural Network (CNN) and Gated Recurrent Unit (GRU) for detecting PD at an early stage. We have used the Parkinson’s Progression Markers Initiative (PPMI) dataset 3D brain images and archived the 86.67%, 94.02%, accuracy of models, respectively.

Pattern of Nonmotor Symptoms in Patients with Idiopathic Parkinson's Disease in a Tertiary Care Hospital of Rural Eastern India.

Idiopathic Parkinson's disease (IPD) is associated with a spectrum of nonmotor symptoms (NMS) that contribute as much to the burden of the disease as the more obvious motor abnormalities. There is a paucity of literature determining the association between NMS and the severity of IPD, especially in rural eastern parts of India. This study explores the frequency of NMS in patients with IPD and determines the association between NMS and the severity of IPD. A cross-sectional observational study involving 65 serially enrolled IPD patients (diagnosed as per United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria) was conducted over a period of 18 months. The patients were evaluated for disease severity as per the Hoehn and Yahr scale (original) and were subsequently evaluated with a predesigned and validated Parkinson's Disease Non-Motor Symptoms Questionnaire. Pearson's Chi-squared test for independence of attributes or Fisher's exact test was used for comparison of categorical variables across the groups. Continuous variables were compared using a one-way analysis of variance (ANOVA) test. The most common presenting NMS of IPD was low mood (n = 61; 93.85%), followed by apathy (n = 59; 90.77%), impaired concentration (n = 58; 89.23%), restless leg (n = 54; 83.08%), and tenesmus (n = 54; 83.08%). A majority of the neuropsychiatric symptoms, autonomic dysfunctions, sleep abnormalities, gastrointestinal manifestations, and sensory abnormalities individually showed a statistically significant relation with the severity of IPD. Common presenting NMS include neuropsychiatric manifestations, autonomic symptoms, sleep-related symptoms, and gastrointestinal manifestations. Most of the NMS are significantly related to disease severity.

Age-dependent deficits of auditory brainstem responses in juvenile Neurexin1α knockout rats.

Abnormal sensory processing is core to neuropsychiatric and neurodevelopmental disorders, such as schizophrenia and autism spectrum disorders. Developing efficient therapies requires understanding the basic sensory pathways and identifying circuit abnormalities during early development. Auditory brainstem responses (ABRs) are well-established biomarkers for auditory processing on the brainstem level. Beyond their advantage of being easily applicable in clinics (given their non-invasive nature), ABRs have high reproducibility in rodents and translate well to humans (e.g. wave identity), despite species differences (e.g. wave features). We hypothesized that ABRs would reveal sensory abnormalities in neurodevelopmental models with construct validity, such as Neurexin1α knockout (Nrxn1α KO) rats during their development. In a previous study, adult Nrxn1α KO rats showed altered cortical auditory-evoked potentials and impaired prediction error to auditory stimuli (Janz in Transl Psychiat, 12:455, 2022 ). This study used ABR measurements to assess brainstem physiology during auditory processing in Nrxn1α KO rats and their wild-type littermates. Therefore, we followed the development trajectories of ABRs from the age of 3weeks to 12weeks longitudinally. We found that juvenile Nrxn1α KO rats (3weeks of age) show altered ABRs, which normalized during further development. This alteration was confined to increased latency in waves II, III, and IV of the ABRs, suggesting impaired auditory processing on the level of the superior olivary complex and inferior colliculus. In conclusion, our results suggest that early but transient deficits in the processing of auditory information on the level of the brainstem are present in Nrxn1α KO rats, which may contribute to later cortical auditory processing deficits observed in adulthood. Our study emphasizes the value of ABRs as a functional readout of auditory brainstem circuit function with potential value as a translational biomarker.

CENTRAL POST-STROKE PAIN: A SCOPING REVIEW

Introduction: Central post-stroke pain (CPSP) is a neuropathic pain syndrome that can affect individuals who have suffered a stroke and which is still under-recognized by doctors. CPSP has an estimated prevalence of 11% and is more common in lesions involving the thalamus. Diagnosis is challenging due to the variable clinical manifestations and the lack of specific diagnostic criteria. The study aims to gather up-to-date information on this condition and highlight the importance of its early recognition. Methodology: This is a descriptive review of the literature in Medline databases, including articles from 2014 to 2024. A total of 468 articles were initially found, of which 43 were selected after applying inclusion and exclusion criteria. Results and discussion: Risk factors were identified as involvement of the spinothalamic pathway, presence of sensory deficits, female gender, young age, and initial stroke severity. The clinical characteristics of CPSP include pain and sensory abnormalities in the regions corresponding to the injured brain territory. The differential diagnosis includes other etiologies, such as post-stroke spasticity, complex regional pain syndrome, headache and shoulder pain. CPSP has a significant impact on quality of life and is associated with psychological disorders and functional limitations. Conclusion: It is understood that early recognition and appropriate management of CPSP are essential for improving patients' quality of life, highlighting the need for clear diagnostic criteria and effective treatments.

How safe is high-intensity focused ultrasound? An intriguing solution for obstetric and gynecological diseases: A systematic review.

High-intensity focused ultrasound (HIFU) is a non-surgical and noninvasive treatment modality that depends on external ultrasound energy sources that induce focused mass ablation and protein degeneration in the treatment area via thermal energy penetration under the intact skin. We aim in our study to collectively evaluate the safety of HIFU for the treatment of different obstetric and gynecological diseases in the literature. We searched PubMed, Scopus, and Science Direct databases, without restriction on date or language, from the inception of these databases until January 20, 2024. We also examined the references of the included studies in the Mendeley archive for eligible articles. We found a total of 706 studies. After the screening and selection process, 56 participants were included. Our dichotomous outcomes were pooled in our single-arm meta-analysis as risk ratio (RR) and with 95% confidence interval (CI) while our continuous outcomes were pooled as mean change and 95% CIs. Fixed- or random-effects models were applied depending on the heterogeneity detected. Our systematic review and meta-analysis included 56 studies including 11.740 patients. Depending on the Society of Interventional Radiology (SIR) classification for adverse effects. The results of this meta-analysis for the type A category that did not require clinical intervention found that pain in the treatment site estimated RR with 95% CI: 0.61 (0.33, 0.89), abnormal vaginal discharge 0.16 (0.073, 0.24), low-grade fever (<38 °C) 0.005 (0.002, 0.009). Sensory abnormalities of the lower limbs were examined in 3390 individuals and observed in only 19 patients who experienced gradual relief of symptoms within one month after treatment. Regarding SIR type B, 99 of a total of 6.437 patients had small vesicles and superficial burns with pooled RR and 95% CI: 0.012 (0.007, 0.018). In terms of groin or perianal and lower abdominal pain, our RRs with 95% CIs were 0.1 (0.067, 0.13) and 0.38 (0.25, 0.51). However, vaginal bleeding was detected in only 32 out of a total of 3.017. Major adverse events like lumber disc herniation, thrombocytopenia, and renal failure, were unmentionable. Additionally, our included studies did not record any deaths. HIFU, either alone or in combination with oxytocin or any other enhancing agent, is safe for patients with different gynecological and obstetric diseases. In terms of efficacy, it showed promising results compared with traditional treatment lines. To our knowledge, we are the first and most comprehensive meta-analysis in the literature that has studied the different safety outcomes related to HIFU as a treatment modality for different obstetric and gynecological diseases with a very large sample size, making our evidence strong and less attributed to errors.

A GUDA AGNIKARMA FOR THE MANAGEMENT OF MANYASTAMBHAA WITH SPECIAL REFERENCE TO CERVICAL SPONDYLOSIS: A CASE STUDY

Background: Manyastambhaa, akin to cervical spondylosis in modern medicine, is prevalent due to lifestyle factors such as poor posture and stress. It is characterized by stiffness and neck pain, and it significantly negatively influences quality of life, especially in the elderly. The slight relief that conventional treatments provide often leads to the investigating of alternative therapies. Methodology: The 67-year-old male patient in this case study has persistent neck discomfort, stiffness, and sensory abnormalities that are not improving with allopathic medicine. The patient received a parasurgical Ayurvedic treatment called Guda Agnikarma therapy. Over ten days, sessions were held on alternate days. The Visual Analog Scale (VAS) and range-of-motion assessments were among the subjective and objective methods used to evaluate pain, stiffness, and discomfort. Observation: After the treatment, there was a noticeable improvement. There was a significant reduction in stiffness and a noticeable discomfort alleviation from severe to none. Flexion, extension, lateral flexion and rotation substantially improved range of motion. Conclusions: Guda Agnikarma showed promise in reducing cervical spondylosis symptoms by acting as an analgesic, reducing inflammation, and relaxing muscles. The method is suitable for outpatient settings, minimally invasive, and reasonably priced. These results point to Guda Agnikarma as a potential treatment for Manyastambhaa, indicating that more research is necessary to confirm its effectiveness and incorporate it into general therapeutic practice.

Early Diagnosis of CNS Virus Infections from Neurological Autoimmune Diseases: A Cross-Sectional Study from China in ER Setting.

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases.