People living with a neurological condition face many difficulties in daily life, impacting their function and quality of life (QoL). There is currently no cure to many neurological conditions, therefore identifying interventions to improve QoL is of high importance. COVID-19 changed society in many ways and understanding the research priorities from the neurological community post pandemic is urgently needed to ensure resources are used efficiently and aligned with the needs and priorities of the community. To better understand the priority areas, it is essential for individuals with lived experience to have input into priority areas for research. Therefore, the aim of this study was to identify the top research priorities for the neurological community in Australia. This priority setting study had two phases. The first phase comprised a face-to-face full day workshop held in late 2019 where participants were led through rounds of brainstorming, categorising and prioritising to reach consensus on a set of research priorities. The second phase was conducted in 2023 with an online survey distributed widely to gauge whether the initial set of research priorities had changed following the event of the global pandemic. On completion of the 2019 workshop there were a total of 27 priority areas with the top priority being diagnosis and early intervention. The 2023 survey results saw mental health and wellbeing moving up one position to become the highest priority. Mental health and wellbeing moving from second in 2019 to first in 2023, shows a need for more resources and research into this area for the neurological community. Many participants suggested that mental health is at the centre of their condition and when their mental health is poor it impacts all areas of their life. The research priorities identified in this study provide direction for researchers about what is important to people living with a range of neurological conditions, allowing researchers to focus on the needs of this community. The data collection phase was planned in collaboration with the Consumer and Community Health Research Network, a consumer advocacy organisation. We partnered with people living with neurological conditions for the data collection for both phases and they gave feedback on the findings.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment with significant improvements in survival rates. With the increase in ICI use in the clinical setting, several case reports and series have described neurological adverse events associated with it. We conducted this systematic review and meta-analysis to estimate the incidence of neurological adverse events among ICI clinical trials. We searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 25, 2025, using ICI and clinical trial as keywords along with their related MeSH terms. The inclusion criteria involved clinical trials investigating the efficacy or safety of any ICI as the only systemic therapy among never treated patients with cancer. To eliminate the impact of other systemic therapies, trials that used ICIs as an adjuvant to another systemic treatment or included patients previously treated with any systemic therapies were excluded. The incidence and its 95% confidence interval (95%CI) were used as the effect measures in the analysis. Subgroup analyses were conducted based on the type of cancer and number of ICIs used in the trial. We included a total of 8,826 patients with cancer from 31 clinical trials. The pooled incidence of neurological adverse events was 1.78 × 10-3% (95%CI 1.06 × 10-3%-2.78 × 10-3%). There was no difference (p = 0.481) in the incidence of neurological side effects between trials that used one ICI (1.83 × 10-3%; 95%CI 0.81 × 10-3%-3.22 × 10-3%) compared to those that used two ICIs (0.90 × 10-3%; 95%CI 0.01 × 10-3%-2.64 × 10-3%). There was also no significant difference (p > 0.622) in the incidence among patients with hepatocellular carcinoma (HCC) (1.20 × 10-3%; 95%CI 0.01 × 10-3%-3.67 × 10-3%), non-small cell lung carcinoma (NSCLC) (1.83 × 10-3%; 95%CI 0.01 × 10-3%-6.0 × 10-3%), and melanoma (1.16 × 10-3%; 95%CI 0.22 × 10-3%-2.71 × 10-3%). The most common neurological adverse events were peripheral neuropathy (1.34 × 10-3%; 95%CI 0.61 × 10-3%-2.3 × 10-3%), myositis (0.78 × 10-3%; 95%CI 0.29 × 10-3%-1.49 × 10-3%), aseptic meningitis (0.71 × 10-3%; 95%CI 0.25 × 10-3%-1.40 × 10-3%), autoimmune demyelinating polyneuropathy (0.66 × 10-3%; 95%CI 0.21 × 10-3%-1.32 × 10-3%), epilepsy (0.66 × 10-3%; 95%CI 0.21 × 10-3%-1.32 × 10-3%), and myasthenia gravis (0.66 × 10-3%; 95%CI 0.21 × 10-3%-1.32 × 10-3%). Taken all together, the incidence of ICI-related neurological adverse events among patients with cancer is low and estimated at 1 in 5000 patients. Individual data analysis of ICI clinical trials is needed to examine the factors associated with ICI-related neurological adverse events.
One in six people in the UK live with a neurological condition, of which many experience bladder, bowel and sexual dysfunction that are present during the time of neurological diagnosis. However, it not clear whether their bladder, bowel or sexual symptoms are considered when formulating a neurological diagnosis. This study aimed to explore the patients experiences of being diagnosed with and managing neurological conditions and the considerations of their bladder, bowel and sexual symptoms. Semi-structured qualitative interviews were conducted with patients with a diverse range of neurological conditions. Interviews were recorded and transcribed verbatim and analysed using reflexive thematic analysis. A patient and public involvement group supported the pilot testing of the topic guide and the data analysis. Twenty participants (12 female, 1 non-binary and 7 male) aged between 30 and 83 and 13/20 people from the global majority participated in the study. Four themes and ten subthemes were identified: (1) Challenges within healthcare - dismissive encounters with healthcare professionals and systemic pressures directly impacting care. (2) Understanding and Advocacy - insufficient communication, education and expectation management across contexts, "I am the ruler of my own self"- self advocacy is essential and peer support. (3) Emotional and Psychological Impact - Grief - "you go through the grieving cycle; you've lost a bit of yourself" and difficulty describing sensations. (4) Sex Matters - Gender differences and sex remains a low priority within healthcare. The findings demonstrate that during diagnosis of neurological conditions bladder bowel and sexual symptoms are overlooked in building the clinical picture, and the needs of managing these emotionally challenging and difficult symptoms are not being effectively met by the healthcare system at present.
To evaluate 2-year neurological outcomes after postoperative neurological deficits (PND) following spinal deformity surgery according to transcranial motor-evoked potential (TcMEP) alert status, and to examine delayed TcMEP deterioration during wound closure. We retrospectively reviewed 1472 patients who underwent spinal deformity surgery with intraoperative neurophysiological monitoring. The primary analysis included 49 patients with PND, stratified by TcMEP alert status. The primary outcome was residual neurological deficit at 2 years. PND occurred in 49/1472 patients (3.3%). Residual deficits were more frequent in alert-negative than alert-positive cases (8/15 [53.3%] vs 6/34 [17.6%], p = 0.017). Among alert-positive PND cases, no residual deficits were observed in responded cases, defined as full-responded or partial-responded cases (0/4 [0.0%]), whereas 6/30 non-responded cases (20.0%) had persistent deficits. In the cohort excluding adult spinal deformity (non-ASD), residual deficits were confined to alert-negative cases (6/7 [85.7%] vs 0/14 [0.0%], p < 0.001). In the exploratory cohort requiring temporary rod removal (n = 37), 13/37 TcMEP alerts (35.1%) occurred during wound closure, at a median of 19 min after deformity correction. Among patients with PND, those without intraoperative TcMEP alerts had poorer 2-year outcomes, particularly in the non-ASD cohort. Alert-negative events may reflect limited detection of isolated nerve root injuries, alert-threshold selection, or monitoring termination before evolving spinal cord compromise becomes detectable. Continued TcMEP monitoring through completion of skin closure may be considered in selected cases when delayed spinal cord compromise is suspected.
Clinical-neurological examination may underestimate internuclear ophthalmoplegia (INO). We investigated immersive virtual reality (VR)-based eye-tracking in patients with multiple sclerosis (MS), other neurological disorders (ND), and healthy controls (HC) to detect INO. In this prospective monocentric study, 471 participants (243 MS, 104 ND, 124 HC) underwent horizontal prosaccade testing (± 10°, ± 20°) using VR-based oculography. INO was determined in a blinded manner based on software-generated reports comparing adduction and abduction velocities. VR-based and clinical assessments were compared using Cohen's kappa (κ). Associations with demographic and clinical variables were analyzed using logistic regression. VR-based assessment identified 43 cases of INO (40 ND, 3 HC). Agreement between VR-based and clinical assessment was moderate (κ = 0.42; 92.5% observer agreement; n = 414). Three cases were identified clinically only, whereas 28 were detected by VR-based assessment only. Within MS, agreement was similar (κ = 0.45; 89.1% agreement; n = 238), with 23 cases detected by VR only and three clinically only. In MS, VR-based INO was associated with male sex (p = 0.035), higher expanded disability status scale (EDSS) and brainstem functional system scores (p < 0.001), longer disease duration and older age (p = 0.002), and visual complaints (p = 0.007). In multivariable analysis, disease duration (OR 1.12, 95% CI 1.01-1.24), brainstem involvement (OR 21.59, 1.30-358.07), and clinical INO (OR 8.18, 1.43-46.96) were associated with VR-based INO. VR-based eye-tracking showed moderate agreement with clinical assessment and identified additional cases of INO associated with markers of disease burden. These findings support further evaluation of VR-derived measures as complementary digital biomarkers of brainstem dysfunction.
Artificial Intelligence (AI) has become integral to the research of neurological diseases due to the rapid expansion of neuroimaging, clinical, physiological, and wearable data. However, the concise synthesis of recent machine learning (ML) and deep learning (DL) remains limited. This systematic review analyzes studies published between January 2021 and March 2026 on five major conditions- Alzheimer's disease, stroke, Parkinson's disease, brain tumors, and traumatic brain injury (TBI)-following the PRISMA 2020 guidelines and a structured search of PubMed, Scopus, and Web of Science, yielding 206 eligible articles. The results show that convolutional and encoder-decoder architectures dominate imaging tasks, whereas hybrid and multimodal approaches increasingly combine imaging with clinical and sensor data. Emerging paradigms, including federated learning, self-supervised learning, and foundation models, address data scarcity, privacy, and cross-institutional variability. Key advances include high-performing transformer-based models for Alzheimer's diagnosis, real-time stroke detection by CT/MRI, improved Parkinson's detection by multimodal fusion, hybrid models for brain tumor classification, and outcome prediction in TBI. Despite these gains, challenges in generalizability, interpretability, and clinical translation persist, underscoring the need for more robust and clinically reliable AI systems to address these issues.
Proton pump inhibitors (PPIs) are widely prescribed, yet their long-term effects on vitamin B12 status remain debated with inconsistent findings across studies. Data from Saudi Arabia and the Middle Eastern primary-care context are limited. To evaluate changes in serum vitamin B12 levels following ≥6 months of PPI therapy and assess the association between PPI use and vitamin B12 deficiency. Retrospective chart-review cohort study with paired pre-post design. Family Medicine clinics at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia (2016-2022). Adults (≥18 years) receiving PPI therapy for ≥6 months with paired vitamin B12 measurements were included. Patients with conditions or medications affecting B12 absorption (metformin, gastrointestinal surgery, atrophic gastritis, vegetarian diet) were excluded. Paired pre-post vitamin B12 levels were compared using Wilcoxon signed-rank and McNemar tests. Neurological symptoms were documented from clinical records. Change in serum vitamin B12 concentration, incidence of vitamin B12 deficiency (<200 pg/mL), and prevalence of neurological symptoms. 376 adult PPI users. Most participants were aged ≥56 years (n=282, 75%), female (n=211, 56.1%), and overweight/obese (n=308, 81.9%). Median vitamin B12 declined significantly from 312 to 297 pg/mL (P<.001), with vitamin B12 deficiency prevalence increasing from 8.2% (n=31) to 12.2% (n=46) (P=.05). New-onset deficiency developed in 9.6% [Author: Please insert n for context, e.g., 9.6% (n)] of patients, with lower baseline B12 predicting greater decline. Neurological symptoms were nearly four times more common among those who developed deficiency (42.4% [95% confidence interval, CI 27.2-59.2] vs. 10.9% [95% CI 7.9-14.8], P<.001). No significant associations were observed with age, sex, BMI, PPI type, or duration. The mean change in serum vitamin B12 was -41.3 pg/mL (95% CI -67.1 to -15.5) and the McNemar paired odds ratio for new-onset deficiency was 1.83 (95% CI 1.00 to 3.46). PPI use for six months or longer was associated with significant vitamin B12 decline, with neurological symptoms more frequent among deficient individuals. These findings support periodic vitamin B12 monitoring and structured deprescribing strategies, particularly for high-risk individuals. Retrospective design, single-center setting, and inability to assess dietary B12 intake or PPI adherence.
Traumatic brain injury (TBI) continues to be one of the world's top causes of mortality and long-term disability. It is a severe and frequently fatal disorder. Patients with traumatic brain injury (TBI) not only sustain neurological impairment but also undergo significant metabolic changes and psychological stress, which may affect their ability to recover. The purpose of this study was to investigate the nutritional determinants and epidemiological trends linked to outcomes in traumatic brain injury patients. This prospective cohort study was carried out at the Imam Reza Hospital's Trauma Department in Tabriz, Iran. Over the course of six months, 520 patients with moderate-to-severe traumatic brain injury were consecutively enrolled, and they were monitored for one month following their release from the hospital. Clinical findings, radiographic results, laboratory data, therapies, outcomes, mechanisms of injury, and demographics were all methodically documented. BMI and serum albumin levels were used at discharge and one-month follow-up to evaluate nutritional status. The Impact of Event Scale (IES) and the Hospital Anxiety and Depression Scale (HADS) were used to assess psychological status. Descriptive techniques, correlation analyses, paired comparisons, and receiver operating characteristic (ROC) curve analysis were among the statistical techniques used to evaluate the standalone discriminatory ability of psychological and nutritional variables. The mean age of the patients was 32.49 ± 13.78 years, and 71.7% were male. Nearly 75% of injuries were caused by falls, making them the most frequent cause. In total, 51.2% of patients passed away while in the hospital, whereas 48.8% of patients survived discharge. Discharge and one-month Glasgow Coma Scale (GCS) scores demonstrated a substantial correlation with outcome (p < 0.001), and neurological severity was strongly associated with survival. Survival, neurological improvement, and psychological distress did not significantly correlate with either discharge or follow-up BMI. Additionally, there was no significant correlation between serum albumin levels and survival, anxiety, depression, or symptoms of post-traumatic stress disorder. BMI, HADS, and IES all showed poor outcome discrimination, and ROC analyses supported their limited standalone discriminatory ability. In this cohort of patients with moderate-to-severe TBI, BMI and serum albumin were not associated with survival or psychological distress and showed limited standalone discriminatory ability for short-term outcomes. These findings suggest that recovery after TBI cannot be adequately characterized by simple nutritional indices alone and support the use of more comprehensive, multidimensional approaches to nutritional and prognostic assessment in TBI survivors.
Thoracolumbar burst fractures are among the most common spinal injuries, and optimal surgical management remains controversial. Evidence comparing posterior-only and combined anterior-posterior fixation strategies remains inconsistent. A systematic search of PubMed, Scopus, Cochrane Library, and Google Scholar was conducted up to November 2025 to identify comparative studies evaluating posterior-only versus combined anterior-posterior fixation for thoracolumbar burst fractures. Nineteen studies (predominantly retrospective; 15 non-randomized and 4 randomized) met inclusion criteria, comprising 1553 patients. Outcomes included perioperative parameters (operative time, blood loss, hospital stay), neurological recovery (Frankel scores), pain and functional outcomes (VAS, ODI, RMDQ, return-to-work rates), radiological parameters (Cobb angle correction, canal compromise recovery), and complication rates (infection, instrumentation failure, pulmonary complications). Posterior-only fixation was associated with significantly reduced blood loss (MD = - 438.21 mL, p < 0.001), shorter operative time (MD = - 121.66 min, p < 0.001), and shorter hospital stay (MD = - 5.62 days, p < 0.001), although heterogeneity was substantial for perioperative outcomes. Pulmonary complications were also lower in the posterior group (RR = 0.16, p = 0.009). No significant differences were found between approaches in neurological improvement, pain scores, functional recovery, radiological correction, infection rates, or instrumentation failure. Both posterior-only and combined anterior-posterior fixation show broadly similar neurological, radiological, and functional outcomes in thoracolumbar burst fractures. Posterior-only fixation was associated with perioperative advantages and a lower risk of pulmonary complications. Surgical decision-making should therefore be individualized based on fracture morphology, neurological status, and patient-specific factors, particularly given that most included evidence remains observational.
Cardiac arrest in pregnancy can occur for a variety of reasons. During maternal cardiac arrest or shortly thereafter, the fetus may remain viable. Postmortem caesarean section can potentially save the fetus with or without long-term neurological sequelae; in the absence of timely intervention, however, fetal death is inevitable. Given the limited documentation in developing countries and the possibility of unfavourable outcomes, this report presents one of the few documented cases from resource-limited Sub-Saharan Africa describing a live birth with a sustained favourable neurological outcome following a postmortem caesarean section performed after maternal death from a dental abscess. This case expands the evidence base for the feasibility and value of such a procedure in settings lacking advanced critical care. We report the case of a 34-year-old multigravida at a gestational age of 36 weeks and 2 days, who was admitted to Sumbawanga Regional Referral Hospital as a referral from a lower facility, presenting with a painful left jaw swelling and a diagnosis of dental abscess. She had a one-month history of this swelling associated with fever, hoarseness of voice, and purulent discharge. Abdominal examination revealed a gravid uterus with fundal height of 36 cm, longitudinal lie, and cephalic presentation. There were no palpable contractions, and the fetal heart rate was 143 bpm. The patient was managed as a case of dental abscess in a near-term pregnancy. The dental team performed incision and drainage, and during the procedure, the patient developed cardiorespiratory arrest attributed to endotoxic septic shock secondary to the dental abscess. The exact cause of death, beyond endotoxic shock, could not be determined in the absence of an autopsy, and other potential causes of death cannot be definitely ruled out. Despite resuscitation attempts, the patient could not be saved and was pronounced dead. In consultation with the Obstetric team, an immediate postmortem caesarean section was performed, delivering a female neonate weighing 2600 g with an APGAR score of 6 and 8 in the 1st and 5th minutes, respectively. The newborn was admitted to the neonatal care unit for further management. At the time of this publication, the child is one year and nine months old and has no apparent neurological impairment, with normal developmental milestones. Despite several limitations and the possibility of poor neonatal outcomes, a timely postmortem caesarean section performed at a favourable gestational age, in an appropriate setting with skilled personnel, basic equipment, and access to a neonatal care unit, can result in a live birth with good early neonatal outcomes even in a resource-limited environment.
Autism is a heterogeneous neurodevelopmental condition arising from complex interactions between genetic susceptibility and environmental factors. Lithium, a naturally occurring element used therapeutically for bipolar disorder and present in food and drinking water, warrants careful evaluation because it readily crosses the placenta and modulates biological pathways critical for brain development. We conducted a structured literature review of PubMed, Embase, and Web of Science through February 20, 2026, and identified 72 human, animal, and in vitro studies examining lithium exposure in relation to autism or neurodevelopmental outcomes. Epidemiologic evidence remains limited, with few studies directly assessing prenatal exposure and insufficient evidence to establish environmental lithium exposure as a neurodevelopmental risk factor. Most human clinical studies reflect therapeutic contexts and demonstrate the mood-stabilizing effects of lithium, whereas human biomarker and experimental studies provide evidence for modulation of glycogen synthase kinase-3β (GSK3β) signaling and thyroid function. Experimental studies indicate that lithium can normalize disease-associated phenotypes in autism-relevant models, yet it also induces behavioral and neurological alterations in non-mutant control models, particularly following high-dose or prenatal exposure. Across evidence streams, convergent findings implicate phosphatidylinositol-calcium signaling, GSK3β-dependent pathways, glutamatergic synapse function, and thyroid hormone regulation, supporting the biological plausibility of lithium-related neurodevelopmental effects. Overall, lithium-associated neurodevelopmental effects appear dose-, context-, and timing-dependent. Knowledge gaps remain regarding environmentally relevant prenatal exposures and long-term neurodevelopmental outcomes, underscoring the need for rigorous epidemiologic and mechanistic studies incorporating refined exposure assessment, developmental timing, and genetic susceptibility.
Recent advances in connectomics have been led by high-resolution reconstruction of large volumes of neural tissues using electron microscopy (EM), providing unprecedented insights into brain structure and function. Dendritic spines-dynamic protrusions on neuronal dendrites-play crucial roles in synaptic plasticity, influencing learning, memory, and various neurological disorders. However, current spine analysis methods often rely on manual annotation of subcellular features, limiting their ability to handle the complexity of spines in dense dendritic networks. This paper introduces a novel automated computational framework that integrates discrete differential geometry, machine learning, and 3D image processing to analyze dendritic spines in these intricate environments. By generating distributions of spine morphology from high resolution images including many thousands of spines, our approach captures subtle variations in spine shapes, offering a nuanced understanding of their roles in synaptic function. This framework is tested on multiple EM datasets, with the aim of enhancing our understanding of synaptic plasticity and its alterations in disease states. The proposed method is poised to accelerate neuroscience research by providing a scalable, objective, and comprehensive solution for spine analysis, uncovering insights into the role of spine geometry for neural function.
Infective endocarditis (IE) is a life-threatening disease characterized by various systemic complications, including neurological manifestations. Although subarachnoid hemorrhage (SAH) is a rare complication of IE, particularly in the absence of aneurysms, the underlying pathophysiological mechanisms remain poorly understood. We report a rare autopsy of a man in his 50s who suddenly died without medical intervention. Postmortem imaging and autopsy showed bilateral convexal SAH (cSAH). Histological examination confirmed IE with gram-positive bacterial colonies in the mitral valve and septic embolization in several organs. In the subarachnoid hemorrhage, gram-positive bacterial colonies and multiple vessels with intense neutrophilic infiltration were observed. These findings provide rare pathological evidence that cSAH can be caused by septic emboli-induced vascular destruction, independent of aneurysmal rupture. This case highlights the need for clinicians and forensic pathologists to consider IE in unexplained deaths with elevated inflammatory marker levels and SAH, even when no cerebral aneurysms are detected. Prompt diagnosis and treatment could be lifesaving in similar cases. To the best of our knowledge, this is an exceptionally rare case report documenting histological confirmation of non-aneurysmal SAH secondary to IE in a forensic autopsy.
Central demyelinating disorders, notably myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), exhibit diverse clinical and radiological manifestations, thereby complicating accurate diagnosis. We present the case of a 78-year-old female patient who developed progressively worsening bilateral lower limb numbness and weakness, accompanied by fecal incontinence over a two-month period. Spinal MRI identified a longitudinally extensive lesion within the spinal cord, and serological analysis revealed MOG antibodies at a titer of 1:100. The patient experienced partial clinical improvement following glucocorticoid treatment, with no further neurological decline. Nevertheless, subsequent spinal magnetic resonance angiography uncovered a spinal arteriovenous malformation. This case underscores the potential diagnostic overlap between demyelinating and vascular myelopathies and highlights that partial responsiveness to steroids and the presence of specific antibodies do not preclude concurrent vascular pathology. Therefore, comprehensive diagnostic assessment, including vascular imaging, is warranted in patients exhibiting atypical or progressive myelopathy despite evidence suggestive of immune-mediated disease. These observations emphasize the clinical heterogeneity inherent to central demyelinating disorders and contribute valuable insights into the neuroimmunological and diagnostic challenges associated with such conditions.
Migraine is a highly prevalent neurological disorder which is more common in women. Clinically, there are two subtypes of menstrual migraine, including pure menstrual migraine (PMM) and menstrually-related migraine (MRM). The former experiences migraine attacks only during the perimenstrual period, while the latter experiences migraine attacks during the perimenstrual period and at other times of the menstrual cycle. MRM accounts for 20-25% of female cases and is associated with greater severity and disability. Although hormonal fluctuations are implicated, the pathophysiology of these subtypes remains poorly understood, and treatment options are limited. Whether PMM and MRM differ clinically or in treatment response has not been systematically compared. This study compared their clinical characteristics and acute treatment responses, which may offer insights into menstrual migraine pathophysiology and help with precise treatment. A cross-sectional study was conducted among 430 female migraine patients recruited from the Headache Specialty Clinic of the First Affiliated Hospital of Soochow University using electronic questionnaires. According to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria, participants were divided into PMM (n = 43) and MRM (n = 322). Concurrently, individuals whose migraine attacks were unrelated to menstruation were classified as NMM (n = 65). This analysis focused on the clinical characteristics and acute medication treatment responses between the PMM and MRM groups. Compared to MRM cases, PMM patients had shorter disease duration (6.8 ± 5.7 vs. 11.1 ± 8.6 years, P < 0.001), fewer prodromal symptoms (58.1% vs. 75.5%, P = 0.016) and accompanying symptoms, including nausea, ocular pain, and osmophobia (all P < 0.05). The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) for acute attacks in the PMM group was superior to that in the MRM group, whether perimenstrual period (96.4% vs. 72.8%, P = 0.010) or non-menstrual period (96.4% vs. 78.3%, P = 0.031). Subgroup analysis of patients with low attack frequency (< 4 per month) confirmed that differences in prodromal symptoms and accompanying symptoms remained between PMM and MRM patients, suggesting that attack frequency alone does not explain these differences. PMM was associated with fewer prodromal and accompanying symptoms, while MRM presented with a broader range of symptoms. In the overall analysis, PMM showed a more favorable response to NSAIDs than MRM; however, this difference did not persist after controlling for attack frequency, suggesting it may be partly attributable to differences in migraine burden. By contrast, differences in prodromal and accompanying symptoms remained significant after adjustment, supporting intrinsic phenotypic distinctions between the two subtypes.
The ipsilateral silent period (iSP) is used to study interhemispheric control of voluntary motor output. It involves a brief suppression of electromyographic (EMG) activity in a muscle during isometric contraction, triggered by Transcranial Magnetic Stimulation (TMS) over the ipsilateral primary motor cortex (M1). The aim of this study was to investigate cortical activity associated with iSP. The study involved 28 healthy right-handed volunteers who performed maximal contractions of the left hand (unimanual) or both hands (bimanual) across conditions with and without TMS. We combined TMS to left M1 with functional Near-Infrared Spectroscopy (fNIRS) over the right hemisphere. EMG was recorded from the hand muscles to quantify the iSP. A significantly greater normalized iSP area was found in the TMS bimanual condition compared to the unimanual one, with a strong correlation between the two. fNIRS revealed higher oxyhemoglobin (HbO) concentration changes in the No TMS condition than in the TMS conditions. Specifically, TMS induced HbO decreases in motor, prefrontal, premotor, parietal, and temporal areas. Reductions in premotor and parietal areas correlated with M1 activity decrease only in unimanual condition. In TMS conditions, a positive correlation was found between fNIRS HbO values in associative parietal cortex and the normalized iSP area: the higher the HbO concentration changes, the greater the inhibition. These findings show reduced M1 activity and demonstrate that a broader frontoparietal network is influenced by the transcallosal motor output. These findings contribute to a better understanding of interhemispheric inhibition and may have implications for the study of neurological disorders.
Benign enlargement of the subarachnoid space (BESS) is a condition characterized by widened subarachnoid spaces, typically associated with macrocephaly or increasing head circumference during infancy or early childhood. Often described as idiopathic and self-limiting, BESS has also been associated with developmental delays and spontaneous subdural collections. Yet, complete interrogation of these associations is limited by lack of normative subarachnoid space characterization and standardized diagnostic criteria. This project aimed to review and synthesize literature on imaging criteria and subarachnoid space measurements for BESS in infants and young children. A systematic PubMed search was conducted using BESS-related terminology, informed by preliminary findings from a manual snowball review. We limited results to reports that provided subarachnoid space measurements from computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US) neuroimaging and investigated subjects with or without BESS and/or macrocephaly from birth to 5 years old. Reports with concomitant neurological conditions affecting brain size were excluded. The final collection included twenty-four reports (US n=10, CT n=6, MRI n=6, multiple n=2), consisting of 2,731 infants and children aged 0-36 months. Most reports evaluated non-BESS/macrocephaly subjects (n=15), followed by BESS and/or macrocephalic subjects (n=3) or both (n=6). Subarachnoid space measurements which were not expressly designated or were without detailed descriptions were the most commonly reported subarachnoid space index measure (n=14), followed by craniocortical width (CCW, n=9). Upper CCW measurements for non-BESS/macrocephaly subjects in US reports ranged from 5 mm to 10.86 mm. In general, for each study that included both non-BESS/macrocephaly and BESS and/or macrocephaly subjects, measurements reported were greater among BESS and/or macrocephaly subjects. There was some evidence of overlapping measurements between the subjects, such as those of CCW measurements in US studies. Overall, substantial variability was observed in imaging methodology and measurement thresholds. This review underscores the need for standardized diagnostic criteria to improve the consistency and reliability of BESS diagnosis.
Perinatal brain injury (PBI) is a major predictor of neurological disability. Commonly associated with prematurity, infection, stroke, hypoxia-ischemia, hemorrhage, and/or toxin exposure, PBI triggers acute and persistent systemic inflammation. There are many stages of vulnerability to PBI during development including pregnancy, birth - term and preterm, and neonatal age. The vulnerable stages can compound inflammation through injury to the placental-fetal-brain axis, adaptive and innate immune system development, neural-immune communication, and central nervous system maturation. Neonates exhibit unique inflammatory signatures and lasting neural-immune responses to various etiologies. Chronic immune dysregulation and priming to a secondary, later-in-life immune challenge defines different forms of PBI while shaping the neonatal and adult immune response with long-term changes. Immunomodulated changes impact regulatory, helper and innate T cells, neutrophils, natural killer cells and immune responsiveness. The major routes of persistent and compounding inflammation in PBI are perinatal neural-immune interactions, cytokine influx, and glial crosstalk. Most treatments are not administered long enough or in the optimal time window to combat sustained inflammation in tertiary and quaternary phases of PBI pathophysiology and are ineffective in reducing neonatal mortality and morbidity and promoting functional recovery. Indeed, persistent systemic and central inflammation is a likely explanation for failed recovery of PBI after the resolution of acute insults. We propose attenuating persistent inflammation and normalizing systemic immune reactivity as key to reducing the functional impact of PBI throughout the lifespan through various avenues including therapeutic treatment, gut microbiome modulation, and novel immunomodulation from preclinical research.
Premature ovarian insufficiency (POI) poses serious neurological risks such as mood disturbances, cognitive decline, early brain structural changes, neural degeneration, and a heightened risk of dementia and AD in women. This study aims to investigate cognitive performance, mitochondrial malfunction, and persistent neuroinflammation in a mouse model of premature ovarian failure induced by ovatoxin vinylcyclohexene diepoxide (VCD), as well as the potential use of dietary phytoestrogen therapy to combat the accelerated brain ageing-like phenotype and chronic inflammation associated with ovarian insufficiency. The data from our neurobehavioural evaluations showed impaired object recognition memory, along with enhanced anxiety and depression in the VCD-intoxicated mice. This was accompanied by a water maze assessment, which indicates that long-term estrogen depletion negatively affected spatial learning and memory retrieval. This is demonstrated by the increased time required for VCD mice to locate the hidden platform and their inability to find the virtual platform during the memory retrieval assessment. In VCD-challenged mice, there were clear signs of compromised learning and memory across the behavioural tests, along with impaired mitochondrial complexes and increased β-amyloid protein expression. Furthermore, in conjunction with reduced estrogen levels, VCD mice showed enhanced neuronal inflammation, as evidenced by heightened expression of neuroinflammatory mediators, including HMGB1, TLR-4, NF-kappa B, CD68 and TREM2. Furthermore, our study has shown that a phytoestrogen diet can restore compromised mood and memory functions. The improvements in learning, memory, and cognitive abilities associated with this dietary intervention were evidenced by reduced neuroinflammation, restored mitochondrial respiratory complexes, enhanced neurotrophic factor levels, and decreased β-amyloid protein expression. Consequently, the current results provide preliminary support for the hypothesis that a diet rich in phytoestrogens could be a viable strategy to mitigate accelerated brain ageing and address mood and memory challenges associated with ovarian insufficiency.