Unexpected arboviruses found in an epidemiological surveillance of acute tropical febrile syndrome in the department of Meta, Eastern Colombia.

BACKGROUND: Nonspecific acute tropical febrile illnesses (NEATFI) are common in the Latin American tropics. Dengue, Chikungunya, Zika, Mayaro, and Usutu, among others, can coexist in the American tropics. This study aimed to surveil the arboviruses that cause| acute febrile syndrome in patients in the Meta department, Colombia. METHODS: Between June 2021 and February 2023, an epidemiological surveillance study was conducted in the Llanos of the Meta department in Eastern Colombia. RESULTS: One hundred patients in the acute phase with typical prodromal symptoms of NEATFI infection who attended the emergency department of the Villavicencio Departmental Hospital were included. ELISA tests were performed for Dengue, Usutu, Chikungunya, and Mayaro. RT-qPCR was performed to detect the arboviruses Usutu, Dengue, Zika, Mayaro, and Oropouche. The seroprevalence for the Chikungunya, Mayaro, and Usutu viruses was 41 % (28/68), 40 % (27/67), and 62 % (47/75), respectively. Seroconversion for Chikungunya was observed in one patient; two seroconverted to Mayaro and one to Usutu. The NS5 gene fragment of the Usutu virus was detected in nine febrile patients. RT-qPCR of the remaining arboviruses was negative. The clinical symptoms of the nine Usutu-positive patients were very similar to those of Dengue, Chikungunya, Zika, and Mayaro infections. CONCLUSIONS: The pervasive detection of unexpected viruses such as Usutu and Mayaro demonstrated the importance of searching for other viruses different from Dengue. Because Usutu infection and Mayaro fever have clinical features like Dengue, a new algorithm should be proposed to improve the accuracy of acute tropical fevers.

Neurologic Symptoms After 177Lu-Prostate-Specific-Membrane Antigen-617 Therapy: A Single-Center Experience.

Treatment with 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after 177Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing 177Lu-PSMA-617 therapy. Methods: The clinical records and imaging data of patients who received their initial dose of 177Lu-PSMA-617 between March 2022 and November 2022 were retrospectively reviewed. All patients presenting for medical evaluation, regardless of specific specialty appointments, with new or worsening neurologic symptoms were included in the study. Results: A total of 185 patients underwent 177Lu-PSMA-617 therapy. The median age was 70 y (range, 58-90 y). The mean follow-up time was 12.04 ± 2.87 mo. Fifty-five new or worsening neurologic symptoms were observed in 50 patients (27%, 50/185). Of these, 27 (11.9%, 27/185) reported altered taste. Eleven patients (6%, 11/185) experienced dizziness with no other clear etiology; 2 of these patients were admitted to the emergency department (ED). Paresthesia symptoms were reported in 6 patients (3.2%, 6/185). Five patients (2.7%, 5/185) reported headaches, 3 of these patients were admitted to the ED because of the severity of the symptoms. Two patients (1.08%, 2/185) presented with extremity weakness. Two patients (1.08%, 2/185) had an ischemic stroke and were admitted to the ED. One patient (0.05%, 1/185) exhibited gait disturbances. In total, 7 patients (3.78%, 7/185) were admitted to the ED because of neurologic symptoms. None of the patients discontinued or failed to complete the 177Lu-PSMA-617 therapy because of neurologic symptoms. Conclusion: After 177Lu-PSMA-617 treatment, the most common neurologic symptoms were dysgeusia and dizziness. In this study, our follow-up period and population size might not have been sufficient to detect delayed or uncommon neurologic symptoms. In patients without neurologic symptoms or central nervous system metastases before treatment, we found the development of severe neurologic problems to be rare and unlikely to require discontinuation of treatment.

Code-ICH: A New Paradigm for Emergency Intervention.

PURPOSE OF REVIEW: Intracerebral hemorrhage (ICH) is the most devastating type of stroke, causing widespread disability and mortality. Unfortunately, the acute care of ICH has lagged behind that of ischemic stroke. There is an increasing body of evidence supporting the importance of early interventions including aggressive control of blood pressure and reversal of anticoagulation in the initial minutes to hours of presentation. This review highlights scientific evidence behind a new paradigm to care for these patients called Code-ICH. RECENT FINDINGS: While numerous trials aimed at decreasing hematoma expansion through single interventions had failed to show statistically significant effects on primary outcomes, time-sensitive, multifaceted, bundled care approaches have recently shown substantial promise in improving functional outcomes in patients with ICH. The concept of Code-ICH can serve as a structural platform for the practice of acute care neurology to continuously measure its performance, reflect on best practices, advance care, and address disparities.

Evaluating the Long-Term Neurologic Sequelae Among Trauma Patients who Received Flexion-Extension Radiographs.

Introduction: This study evaluated the presence of neurologic sequelae among trauma patients after flexion-extension (F/E) radiographs. Methods: Authors of the study conducted a retrospective review of patients (age ≥ 14 years) with a Glasgow Coma Score of 15 who sustained a blunt traumatic injury and received F/E radiographs. Radiographic scans were defined as positive, negative, inconclusive, or incomplete. The neurologic status of each patient was assessed before and after the F/E radiographs, and at discharge and follow-up. Results: Of the 501 patients included in the analysis, 84.6% (n = 424) had negative F/E radiographs, and 3.2% (n = 16) had positive F/E radiographs. Ten percent (n = 51) of patients had incomplete F/E radiographs, and 2.0% (n = 10) were inconclusive due to the inability to rule out a ligamentous injury. Three patients (0.6%) had MRI-confirmed ligamentous injuries, all of which had initial incomplete F/E radiographs due to pain. No patient had a documented neurological deficit before or after the F/E exam. Three patients with an initial negative F/E radiograph returned to the clinic with symptoms of neurologic sequelae. Two of these patients had symptom resolution with no further issues at future follow-up appointments. The third patient was found to have chronic neurologic symptoms after further evaluation. Conclusions: The inclusion of F/E exams in cervical spine clearance protocols did not demonstrate any new long-term iatrogenic neurologic injuries. Consideration should be given to performing MRIs on patients with incomplete F/E radiographs that cannot rule out a ligamentous injury.

Machine learning characterization of a rare neurologic disease via electronic health records: a proof-of-principle study on stiff person syndrome.

BACKGROUND: Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS. METHODS: A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health's EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores-SHapley Additive exPlanation (SHAP) values-for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation. RESULTS: Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795-0.840), sensitivity of 0.766 (95% CI 0.743-0.790), F-score of 0.761 (95% CI 0.744-0.778), AUC of 0.808 (95% CI 0.791-0.825), and accuracy of 0.775 (95% CI 0.759-0.790). CONCLUSIONS: This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs.

Short- and long-term neurological outcomes of congenital cytomegalovirus infection.

Background/aim: Cytomegalovirus (CMV) is the most common congenital viral infection. Although most children with congenital CMV (approximately 85%-90%) are asymptomatic at birth, findings such as sensorineural hearing loss, microcephaly, and neurodevelopmental retardation can be observed during the follow-up. Among the brain magnetic resonance imaging (MRI) findings of CMV are white matter abnormalities, polymicrogyria, and periventricular calcification. Since a definitive diagnosis of congenital CMV cannot be made after the neonatal period, the identification of the associated phenotype is diagnostically important, but data are limited in patients who have been retrospectively diagnosed with congenital CMV infection. The aim of this study was to evaluate the short- and long-term neurological follow-up results of congenital CMV infections in a tertiary hospital. Materials and methods: The neurological results of fifteen patients under the age of 18 years, who had a definitive diagnosis of congenital CMV infection and were followed up in a tertiary care hospital between 2011 and 2020, were retrospectively evaluated. Results: Ten of the patients in our study group were male. The mean age at presentation for neurological evaluation was 2.02 ± 1.54 months, with a median follow-up time of 36.3 months (range: 9.3-129.4 months). Neurological disorders detected during the long-term follow-up included cerebral palsy (46.7%), cognitive impairment (46.7%), epilepsy (40%), and sensorineural hearing loss (26.7%). The most common abnormality observed on MRI scans was white matter involvement (53.3%). Conclusion: Early diagnosis and intervention are crucial in congenital CMV infection, as it commonly results in neurological involvement among the patients in our series. This preventable condition warrants further research regarding prenatal/neonatal screening.

The Role of Diffusion Tensor Imaging in CNS Tuberculosis.

Background and objective Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health concern, with India being a hotspot for the disease burden. Central nervous system (CNS) tuberculosis, though comprising a smaller proportion of total TB cases, is associated with significant morbidity and mortality. This study aimed to explore the utility of diffusion tensor imaging (DTI) in assessing the microstructural changes in white matter tracts associated with CNS tuberculosis. Materials and methods This study was conducted over two years at the All India Institute of Medical Sciences, Rishikesh. We employed a cross-sectional observational design and included patients with definite or highly probable tuberculous meningitis, alongside healthy controls. Results Our findings revealed a significant reduction in fractional anisotropy (FA) values in various white matter tracts of patients with CNS tuberculosis compared to healthy individuals. This reduction in FA correlated with the severity of tuberculous meningitis, particularly in the corpus callosum. Additionally, DTI highlighted distinct patterns of white matter involvement around intraparenchymal lesions, suggesting potential implications for clinical outcomes. The study emphasizes the utility of FA values in grading disease severity and prognosticating treatment outcomes in CNS tuberculosis. Conclusions Overall, this study provides valuable insights into the microstructural alterations in white matter tracts associated with CNS tuberculosis, highlighting the potential of DTI in early diagnosis, grading disease severity, and monitoring treatment response. We believe these findings will pave the way for further research to optimize the clinical management of this debilitating disease.

Can Music Enhance Working Memory and Speech in Noise Perception in Cochlear Implant Users? Design Protocol for a Randomized Controlled Behavioral and Electrophysiological Study.

BACKGROUND: A cochlear implant (CI) enables deaf people to understand speech but due to technical restrictions, users face great limitations in noisy conditions. Music training has been shown to augment shared auditory and cognitive neural networks for processing speech and music and to improve auditory-motor coupling, which benefits speech perception in noisy listening conditions. These are promising prerequisites for studying multi-modal neurologic music training (NMT) for speech-in-noise (SIN) perception in adult cochlear implant (CI) users. Furthermore, a better understanding of the neurophysiological correlates when performing working memory (WM) and SIN tasks after multi-modal music training with CI users may provide clinicians with a better understanding of optimal rehabilitation. METHODS: Within 3 months, 81 post-lingual deafened adult CI recipients will undergo electrophysiological recordings and a four-week neurologic music therapy multi-modal training randomly assigned to one of three training focusses (pitch, rhythm, and timbre). Pre- and post-tests will analyze behavioral outcomes and apply a novel electrophysiological measurement approach that includes neural tracking to speech and alpha oscillation modulations to the sentence-final-word-identification-and-recall test (SWIR-EEG). Expected outcome: Short-term multi-modal music training will enhance WM and SIN performance in post-lingual deafened adult CI recipients and will be reflected in greater neural tracking and alpha oscillation modulations in prefrontal areas. Prospectively, outcomes could contribute to understanding the relationship between cognitive functioning and SIN besides the technical deficits of the CI. Targeted clinical application of music training for post-lingual deafened adult CI carriers to significantly improve SIN and positively impact the quality of life can be realized.

sEMG as complementary tool for VFSS: A synchronized study in patients with neurogenic oropharyngeal dysphagia.

The neurogenic oropharyngeal dysphagia is a prevalent functional swallowing disorder resulting from neurological causes. The conventional diagnosis involves ionizing radiation in Videofluoroscopy Swallowing Studies (VFSS). Surface electromyography (sEMG) offers a non-invasive alternative by recording muscle activity. This research compares bolus passage timing through anatomical structures using VFSS and sEMG-related activation times. Fifty confirmed oropharyngeal dysphagia patients underwent synchronized VFSS and sEMG, evaluating muscle groups during cracker and fluid ingestion. sEMG revealed activation patterns in masseters, suprahyoid, and infrahyoid muscles, occurring before bolus passage through the mandibular line and concluding near the upper esophageal sphincter complex. sEMG identified differences in dysphagia severity (EAT-10 score), age, and diagnosis, contrasting VFSS results. Results indicate potential complementarity between sEMG and VFSS for dysphagia screening, diagnosis, and monitoring.

Facilitators and Barriers to Implementing High-Intensity Gait Training in Inpatient Stroke Rehabilitation: A Mixed-Methods Study.

(1) Background: High-intensity gait training (HIT) is a recommended intervention that improves walking function (e.g., speed and distance) in individuals who are undergoing stroke rehabilitation. This study explored clinicians' perceived barriers and facilitators to implementing HIT utilizing a mixed-methods approach comprising a survey and exploratory qualitative research. (2) Methods: Clinicians (n = 13) who were implementing HIT at three facilities participated. We collected and analyzed data using the consolidated framework for implementation research. Three focus groups were recorded and transcribed, and data were coded and thematically categorized. (3) Results: Survey results identified that the facilitators with a strong impact on implementation were access to knowledge/resources and intervention knowledge/beliefs. The only agreed-upon barrier with a strong impact was lack of tension for change. The focus groups resulted in 87 quotes that were coded into 27 constructs. Frequently cited outer setting facilitators were cosmopolitanism and peer pressure, and the only barrier was related to the patient needs. Innovation characteristics that were facilitators included relative advantage and design quality and packaging, and complexity was a barrier. Inner setting facilitators included networks and communication, learning climate, leadership engagement, and readiness for implementation. However, communication, leadership engagement, and available resources were also barriers. Regarding characteristics of individuals, knowledge and beliefs were both barriers and facilitators. In the implementation process domain, common facilitators were formally appointed implementation leaders and innovation participants. Barriers in this domain were related to the patients. (4) Conclusions: Clinicians identified many barriers and facilitators to implementing HIT that often varied between facilities. Further research is warranted to deepen our understanding of clinicians' experiences with HIT implementation.

Comparative analysis of 'functional excision' of heterotopic ossification around the hip - computed tomography (CT) navigation guided versus conventional excision.

PURPOSE: We aim to analyse and compare the efficacy of the excision of HO around the hip with and without CT-guided navigation. We also aim to compare the functional outcome between CT navigation guided versus conventional excision of HO. PATIENTS AND METHODS: This study is a retrospective analysis of prospectively collected data from 2015 to 2022. There were 23 patients (24 hips) in the final cohort. Intraoperative CT navigation guided excision was performed in 7 hips and conventional excision of HO was done in 17 hips. The HO was classified by Brooker's grading in radiographs. CT scan was taken preoperatively in all patients to exactly identify the volume, location and preoperative planning. The functional outcome was analysed according to Harris Hip Score (HHS) and International Hip Outcome Tool (iHOT) for self-ambulatory patients and improvement in the sitting or nursing care was assessed in patients mobilising with wheelchair or walker support. Any complications or recurrence noted postoperatively and in follow-up were recorded. RESULTS: The mean follow-up was 41.2 months in the CT navigation-guided excision group and 55 months in the conventional excision group. According to Brooker's grading, grade IV was present in 20 hips and grade III in four hips. Twelve patients were self-ambulatory and the other 12 patients were requiring support for mobilisation. There was a significant improvement in the HHS from 21.3 ± 3.7, 18.3 ± 2.5 preoperatively to 75.2 ± 8.3, 72.2 ± 4.3 postoperatively in the CT navigation guided and conventional group respectively (p < 0.001) in the self-ambulatory group. There was one anterior wall and one partial posterior wall fracture in the conventional group. One patient in the conventional group had a deep infection and recurrence. One patient had a superficial infection and another had superficial vein thrombosis in the CT guided excision group. CONCLUSION: Intraoperative CT navigation helps to exactly localize the HO and facilitates safe excision. Functional excision of the HO leads to better nursing care and functional outcomes between both groups.

An International and Multidisciplinary Consensus on the Labeling of Spatial Neglect Using a Modified Delphi Method.

Survivors of neurologic injury (most commonly stroke or traumatic brain injury) frequently experience a disorder in which contralesionally positioned objects or the contralesional features of individual objects are often left unattended or underappreciated. The disorder is known by >200 unique labels in the literature, which potentially causes confusion for patients and their families, complicates literature searches for researchers and clinicians, and promotes a fractionated conceptualization of the disorder. The objective of this Delphi was to determine if consensus (≥75% agreement) could be reached by an international and multidisciplinary panel of researchers and clinicians with expertise on the topic. To accomplish this aim, we used a modified Delphi method in which 66 researchers and/or clinicians with expertise on the topic completed at least 1 of 4 iterative rounds of surveys. Per the Delphi method, panelists were provided with results from each round prior to responding to the survey in the subsequent round with the explicit intention of achieving consensus. The panel ultimately reached consensus that the disorder should be consistently labeled spatial neglect. Based on the consensus reached by our expert panel, we recommend that researchers and clinicians use the label spatial neglect when describing the disorder in general and more specific labels pertaining to subtypes of the disorder when appropriate.

A Case of Anti-Leucine-Rich Glioma-Inactivated Protein 1 (Anti-LGI1) Limbic Encephalitis With Normal Imaging.

Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (anti-LGI1 LE) is a rare autoimmune limbic encephalitis with a potentially misleading presentation that can delay diagnosis and treatment. The incremental progression of widely variable symptoms with a prominent behavioral disturbance can conceal the disease and prompt an initial psychiatric diagnosis. Although specific MRI findings ought to be evident by the time the disease progresses to frank limbic encephalitis, it appears inconsistent and ill-defined and is thus unreliable. Nevertheless, brain imaging remains prominent in the discussion, even included in some guidelines for diagnosing anti-LGI1 LE. Here, we present a case of a patient who presented after a suicide attempt with a long history of psychiatric issues, aberrant "spasms," and subsequently encephalopathy, who was eventually diagnosed with anti-LGI1 LE only after delayed CSF antibodies studies. In this patient, symptoms emerged over two years, with multiple brain MRIs being negative, including the one completed during the hospital admission in focus. The purpose of this case report is to encourage maintaining a broad differential when patients present with bizarre symptoms. This report underlies the importance of thorough clinical evaluation, utilization of multiple diagnostic resources, and the need for heightened awareness among healthcare providers about the subtleties of autoimmune encephalitis presentations. With anti-LGI1 LE already being severely underdiagnosed, it is important to continue reviewing various cases of patients who are diagnosed with anti-LGI1 LE and further review to understand its pathophysiology and common clinical presentation. This case also underscores the ongoing evolution in understanding anti-LGI1 LE and highlights that patients may present with unfamiliar symptoms or diagnostic challenges. The overall objective is to help providers recognize anti-LGI1 LE earlier, so treatment can be initiated sooner, leading to a better prognosis for patients.

Long-read sequencing and optical genome mapping identify causative gene disruptions in noncoding sequence in two patients with neurologic disease and known chromosome abnormalities.

Despite advances in next generation sequencing (NGS), genetic diagnoses remain elusive for many patients with neurologic syndromes. Long-read sequencing (LRS) and optical genome mapping (OGM) technologies improve upon existing capabilities in the detection and interpretation of structural variation in repetitive DNA, on a single haplotype, while also providing enhanced breakpoint resolution. We performed LRS and OGM on two patients with known chromosomal rearrangements and inconclusive Sanger or NGS. The first patient, who had epilepsy and developmental delay, had a complex translocation between two chromosomes that included insertion and inversion events. The second patient, who had a movement disorder, had an inversion on a single chromosome disrupted by multiple smaller inversions and insertions. Sequence level resolution of the rearrangements identified pathogenic breaks in noncoding sequence in or near known disease-causing genes with relevant neurologic phenotypes (MBD5, NKX2-1). These specific variants have not been reported previously, but expected molecular consequences are consistent with previously reported cases. As the use of LRS and OGM technologies for clinical testing increases and data analyses become more standardized, these methods along with multiomic data to validate noncoding variation effects will improve diagnostic yield and increase the proportion of probands with detectable pathogenic variants for known genes implicated in neurogenetic disease.

Effects of PCSK9 Inhibitors on Early Neurologic Deterioration in Patients with Acute Non-Cardioembolism without Hemorrhagic Transformation After Intravenous Thrombolysis.

BACKGROUND: END (Early Neurologic Deterioration) significantly elevates the risk of morbidity and mortality. While numerous studies have investigated END following hemorrhagic transformation post-thrombolysis in acute cerebral infarction research on END without hemorrhagic transformations in patients with acute cerebral infarction due to non-cardiogenic embolism remains scarce. AIM: This study aimed to elucidate the impact of PCSK9 inhibitors on early neurological deterioration (END) in patients with acute non-cardioembolism cerebral infarction without hemorrhagic transformation post-intravenous thrombolysis. Additionally it aimed to identify risk factors associated with END in patients suffering from this type of stroke. OBJECTIVE: The objective of this study is to investigate the effect of PCSK9 inhibitors on early neurologic deterioration (END) in patients with acute non-cardiogenic cerebral infarction without hemorrhagic transformation after intravenous thrombolysis and identify associated risk factors for END in this patient population. METHODS: In this retrospective case-control study the data of consecutive patients who underwent intravenous thrombolysis after AIS (acute ischemic stroke) without hemorrhagic transformation during hospitalization at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 to February 2023 were retrieved and assessed. An increase of >2 in the National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission was defined as END. RESULTS: This study included 250 patients (56 males 22.4%) they were 63.34±12.901 years old. There were 41 patients in the END group and 209 in the non-END group. The usage rate of PCSK9 inhibitors was significantly different between the END group and non-END group (29.268% vs 58.852% P<0.001). The White blood cell count (WBC) and homocysteine levels showed a significant difference between the two groups (all P<0.05). Patients not using PCSK9 inhibitors (OR=0.282 95%CI: 0.127-0.593) and white blood cell count (OR=1.197, 95%CI: 1.085-1.325) were independently associated with END. Receiver-operating characteristic curve analysis suggested that the sensitivity specificity and area under the curve for PCSK9 inhibitors used for END were 88.9%, 80.7% and 0.648 respectively. CONCLUSION: The use of PCSK9 inhibitors can reduce the incidence of early neurological deterioration in patients with acute non-cardioembolism and non-hemorrhagic transformation after intravenous thrombolysis.

Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children.

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; -3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; -1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; -1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

Study protocol of a randomized controlled trial comparing backward walking to forward walking training on balance in multiple sclerosis: The TRAIN-MS trial.

Balance impairment and accidental falls are a pervasive challenge faced by persons with multiple sclerosis (PwMS), significantly impacting their quality of life. While exercise has proven to be an effective intervention for improving mobility and functioning in PwMS, current exercise approaches predominantly emphasize forward walking (FW) and balance training, with variable improvements in balance and fall rates. Backward walking (BW) has emerged as a promising intervention modality for enhancing mobility and strength outcomes; however, significant gaps remain. Specifically, there is limited knowledge about the efficacy of BW interventions on outcomes such as static, anticipatory, and reactive balance, balance confidence, falls, and cognition. This randomized controlled trial aims to determine the feasibility, acceptability, and impact of 8-weeks of backward walking training (TRAIN-BW) as compared to forward walking training (TRAIN-FW). Ninety individuals with MS with self-reported walking dysfunction or ≥ 2 falls in the past 6 months will be randomized in blocks, stratified by sex and disease severity to either the TRAIN-BW or TRAIN-FW intervention groups. Adherence and retention rates will be used to determine feasibility and the Client Satisfaction Questionnaire will be used to assess acceptability. The primary outcomes will be static, anticipatory, and reactive balance. Secondary outcomes include walking velocity, balance confidence, concern about falling, cognition, physical activity, and fall rates measured prospectively for 6 months after post-testing. Additionally, the extent to which cognitive functioning influences response to intervention will be examined. Backward walking training may be an innovative intervention to address balance impairments and falls in persons with MS.

Validation of the Center for Neurologic Study Bulbar Function Scale-Chinese version in a population with amyotrophic lateral sclerosis.

OBJECTIVE: The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. METHODS: A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5-10 days after the first evaluation. RESULTS: The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p < 0.001). The CNS-BFSC total score and sialorrhea and speech scores were significantly correlated with the ALSFRS-R bulbar subscore (p < 0.001). The CNS-BFSC total score and ALSFRS-R bulbar subscale score were highly predictive of a clinician diagnosis of impaired bulbar function (area under the receiver operating characteristic curve, 0.947 and 0.911, respectively; p < 0.001). A cutoff value for the CNS-BFSC total score was selected by maximizing Youden's index; this cutoff score was 33, with 86.4% sensitivity and 93.3% specificity. The CNS-BFSC total score and the sialorrhea, speech and swallowing subscores had good-retest reliability (p > 0.05). The Cronbach's α of the CNS-BFSC was 0.972. CONCLUSION: The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

Persian Translation of the Sport Concussion Assessment Tool 6 (SCAT6); a Cross-Cultural Adaptation and Validation Study.

Introduction: Sport Concussion Assessment Tool (SCAT) aids the physicians in early management of concussion among suspected athletes and its 6th version was published in 2023 in English. This study aimed to describe the translation and validation process of SCAT6 from English to Persian. Methods: The Persian translation of SCAT6 and its evaluation has been done in seven stages: initial translation, appraisal of the initial translation, back translation, appraisal of the back-translation, validation (face and content validities), final reconciliation and testing by simulation. Results: Initial translation, was done by two bilingual translators followed by an initial appraisal, which was made by both translators and one general physician. Back translation was done by two naïve translators who were unfamiliar with SCAT6, followed by its appraisal by initial translators. Face and content validity of the translation were surveyed by medical professionals and athletes and the results of the validation process were provided to the reconciliation committee and this committee made the modifications needed. Finally, the use of Persian SCAT6 was simulated and the mean time needed to complete the Persian SCAT6 was roughly a little more than 10 minutes. Conclusions: The present study provides the readers with the translation and cross-cultural adaptation process of SCAT6 from English to Persian. This translated version will be distributed among the Iranian sports community for assessing concussions among athletes.

Clinical and genetic characteristics of congenital hyperinsulinism in Norway: A nationwide cohort study.

PURPOSE: Congenital hyperinsulinism (CHI) is a rare, monogenic disease characterized by excessive insulin secretion. We aimed to evaluate all probands with suspected CHI in Norway registered over the past two decades. METHODS: The study included 98 probands. Clinical data were cumulated from medical records. All probands were screened for variants in the genes ABCC8 and KCNJ11. Other CHI-related genes were Sanger-sequenced as indicated by the patients' phenotype (N=75) or analyzed by next-generation sequencing employing a panel of 30 CHI-related genes (N=23). RESULTS: Twenty-one probands (21%) received a diagnosis other than CHI, the most common being idiopathic ketotic hypoglycemia (9%) or syndromic hyperinsulinism (4%). In the final cohort of 77 CHI probands, genetic findings were revealed in 46 (60%). ABCC8 variants were most common (N=40) and five novel variants were identified. One proband harbored both the pathogenic GCK variant p.(Ala456Val) and the ABCC8 variant p.(Gly505Cys). Although most ABCC8 variants caused immediate disease onset with severe hypoglycemia and were diazoxide-unresponsive, eight probands had a heterozygous, apparently dominant variant with milder phenotype. Two probands had pathogenic variants in GLUD1, whereas variants in HADH, HNF4A, KCNJ11, and HK1 were identified in one proband each, the latter being non-coding. Neurologic sequelae were reported in 53% of the CHI probands. Of non-surgically treated probands, 43% had spontaneous resolution. The minimum birth prevalence of CHI in Norway is 1:19,400 live births. MAIN CONCLUSIONS: Individuals with disease-causing ABCC8 variants dominated our cohort. Patients with known genetic etiology had earlier and more severe disease-onset than genetically unsolved patients.