Neurological Comorbidities Research Articles

Lobe‐specific changes in white matter volume and myelination following 6‐month 40 Hz gamma sensory stimulation in patients on the Alzheimer’s disease spectrum

AbstractBackgroundAlthough morphometric changes in Alzheimer’s Disease (AD) occur both in gray and white matter, gray matter changes had been the primary focus of previous work. Recent studies have highlighted the importance of pathological changes in white matter and myelination in AD patients, including early changes to oligodendrocytes and transcription of myelin protein genes in the white matter prior to symptoms of cognitive decline, even in subjects with AD but without other neurological comorbidities (Ferrer et al., 2020). Since neuronal activities, particularly network oscillations have been shown to promote myelination, the present study examined how 40Hz gamma stimulation affected white matter volume and myelination in different cortical lobes in patients with AD.MethodData were obtained from the Overture trial (NCT03555281) in which treatment participants received daily, at‐home, 40Hz gamma sensory stimulation for six months, while placebo participants received sham stimulation (treatment‐to‐placebo ratio 2:1). Magnetic resonance imaging (MRI) data were collected at 1.5 Tesla at baseline, month 3, and month 6. MRI T1 images and T1w/T2w ratios were used to estimate volume (N = 38) and myelination (N = 36), respectively. Using Bayesian linear mixed effects modeling, we estimated white matter volume and myelination percent changes with respect to baseline. Treatment group results were reported in relation to the placebo group.ResultWith respect to the placebo group: In the left hemisphere, the treatment group exhibited reduced white matter atrophy in the frontal lobe (‐3.27±1.4, p = 0.0225), in the temporal lobe (‐3.9±1.76, p = 0.0306), in the parietal lobe (‐3.32±1.43, p = 0.0236), in the occipital lobe (‐4.1±1.72, p = 0.0195) and reduced demyelination in the frontal lobe (‐5.13±2.12, p = 0.0186), in the temporal lobe (‐5.33±2.42, p = 0.0321), in the parietal lobe (‐5.7±2.07 (p = 0.0079), in the occipital lobe (‐5.65±2.52, p = 0.0296). In the right hemisphere, the treatment group trended towards reduced white matter volume loss and demyelination in all lobes, however, demyelination was significantly reduced in the parietal lobe (‐4.48±2.09, p = 0.037), and in the occipital lobe (‐5.5±2.22, p = 0.0165).ConclusionWhite matter atrophy and demyelination were statistically significantly reduced in all lobes of the left hemisphere and trended towards reduction in the right hemisphere, demonstrating that 40Hz sensory stimulation can reduce the neurodegeneration associated with AD.

Sleep Disturbances as a Manifestation of Neurodevelopmental Disorders

Sleep disturbances are complex elements of many neurodevelopmental disorders, such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual and developmental disabilities, and insomnia. Sleep disturbances are caused by a variety of factors, resulting in short-term and long-term consequences that can affect self-care, daily functions, and well-being. Sleep disturbances can compromise not only he general health of individuals but also on the health of caregivers and support systems. There is a need to understand the interaction between neurodevelopmental disorders and sleep disturbances to identify patterns of sleep fragmentations contributed to neurobiological and neurodevelopmental conditions determine appropriate treatment, improve the quality of life for individuals with neurological comorbidities.

Expert opinion on diagnosis and management of epilepsy-associated comorbidities.

Apart from seizure freedom, the presence of comorbidities related to neurological, cardiovascular, or psychiatric disorders is the largest determinant of a reduced health-related quality of life in people with epilepsy (PwE). However, comorbidities are often underrecognized and undertreated, and clinical management of comorbid conditions can be challenging. The focus of a comprehensive treatment regimen should maximize seizure control while optimizing clinical management of treatable comorbidities to improve a person's quality of life and overall health. A panel of four European epileptologists with expertise in their respective fields of epilepsy-related comorbidities combined the latest available scientific evidence with clinical expertise and collaborated to provide consensus practical advice to improve the identification and management of comorbidities in PwE. This review provides a critical evaluation for the diagnosis and management of sleep-wake disorders, cardiovascular diseases, cognitive dysfunction, and depression in PwE. Whenever possible, clinical data have been provided. The PubMed database was the main search source for the literature review. The deleterious pathophysiological processes underlying neurological, cardiovascular, or psychiatric comorbidities in PwE interact with the processes responsible for generating seizures to increase cerebral and physiological dysfunction. This can increase the likelihood of developing drug-resistant epilepsy; therefore, early identification of comorbidities and intervention is imperative. The practical evidence-based advice presented in this article may help clinical neurologists and other specialist physicians responsible for the care and management of PwE.

The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies

A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain–Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials.

Elderly Onset of Functional Motor Disorders: Clinical Correlates from the Italian Registry.

Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables. We recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics. Among the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48). These results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

Targeting accelerated pulmonary ageing to treat chronic obstructive pulmonary disease-induced neuropathological comorbidities.

Chronic obstructive pulmonary disease (COPD) is a major incurable health burden, ranking as the third leading cause of death worldwide, mainly driven by cigarette smoking. COPD is characterised by persistent airway inflammation, lung function decline and premature ageing with the presence of pulmonary senescent cells. This review proposes that cellular senescence, a state of stable cell cycle arrest linked to ageing, induced by inflammation and oxidative stress in COPD, extends beyond the lungs and affects the systemic circulation. This pulmonary senescent profile will reach other organs via extracellular vesicles contributing to brain inflammation and damage, and increasing the risk of neurological comorbidities, such as stroke, cerebral small vessel disease and Alzheimer's disease. The review explores the role of cellular senescence in COPD-associated brain conditions and investigates the relationship between cellular senescence and circadian rhythm in COPD. Additionally, it discusses potential therapies, including senomorphic and senolytic treatments, as novel strategies to halt or improve the progression of COPD.

Neurological and neuropsychiatric manifestations in hospitalised patients with COVID-19.

Although literature globally indicates varied neurological and/or neuropsychiatric manifestations (NNM) and complications associated with coronavirus disease 2019 (COVID-19), information about NNM in infected hospitalised patients on the African continent remains limited. To describe the presentation of NNM and compare patients with and without NNM considering demographic and clinical profiles, treatment, and outcomes. Tygerberg Hospital, Cape Town, South Africa. Retrospective medical record review of the first 100 consecutively admitted COVID-19 patients (64 females, mean age 47.6 years) between March and June 2020. Of the 98 patients included in the analysis, 56.1% had at least one NNM. The most common NNM were myalgia (32.7%), headache (21.4%), loss of smell and/or taste (15.3%), and delirium (10.2%). Patients with and without NNM did not differ with respect to demographic characteristics. Patients with NNM had significantly more constitutional symptoms (p = 0.017) and were more likely to have neurological and/or neuropsychiatric comorbid conditions (10.9% vs. 0.0%, p = 0.033) than those without NNM. Patients without documented NNM were more likely to have abnormalities on chest X-ray (p = 0.009) than those with NNM. Coronavirus disease 2019 related treatment and mortality did not differ between the groups. Neurological and/or neuropsychiatric manifestations were common in hospitalised patients with COVID-19. The results suggest that while COVID-19 patients with NNM may have less of a respiratory phenotype they nonetheless have equivalent mortality rates. This study highlights the common NNM in patients with COVID-19 admitted to Tygerberg Hospital early in the pandemic and adds to the growing evidence of COVID-19 NNM.

Abstract 13938: Trends in In-Hospital Implantation of Implantable Cardiac Monitors in the Unites States: 2016-2019

Introduction: Implantable cardiac monitors (ICM) are widely employed for long-term cardiac rhythm monitoring. While a majority of ICMs are implanted on an outpatient basis, national estimates on their use in the inpatient setting are lacking. Methods: The National Inpatient Sample and the National Readmission Database were queried to identify inpatient ICM implantations between 2016 and 2019. Baseline characteristics, in-hospital outcomes, readmission rates, and trends over time were assessed for the study population and compared between the largest diagnostic cohorts: neurologic and cardiac. Results: A total of 101,430 adults underwent in-hospital ICM implantation between 2016 and 2019 (52.9% neurologic, 39.2% cardiac). Patient characteristics and outcomes are shown in Table 1. There was a 170% increase in inpatient ICM procedures from 2016 to 2019. Significant changes in patient profiles and readmission rates were observed over the study period. The trends are shown in Table 2a. After adjusting for confounders, patients with cardiac indications were more likely to have complications and be readmitted, but had lower mortality, length of stay, and hospitalization cost compared with the neurology cohort. The ORs are shown in Table 2b. Conclusions: The number of inpatient ICM implantations has increased significantly, likely reflecting expanding indications. The profiles of patients receiving ICM also changed to include more primary neurologic indications, comorbidities, and non-white races. Small and medium sized hospitals performed the procedure more frequently. Complication rates were extremely low and remained constant during the study period.

The Association of Cardiovascular and Neurological Comorbidities in Geriatric Patients Sustaining Ocular Trauma.

Falls are associated with ocular trauma in the elderly. However, it is unlikely for a fall to cause ocular injury unless there is a disruption in the protective maneuvers that shield the face. We suspect ocular injury may be an early indicator of systemic or neurologic degeneration. This study investigates the 5-year incidence of cardiovascular and neurodegenerative diseases in older patients who sustained ocular or periorbital injuries. This was a retrospective cohort study. The study population included 141 patients over the age of 65 who sustained trauma to the eye, orbit, or eyelid between April 2011 and June 2016. The control population included 141 patients with a similar range of comorbidities who received cataract surgery during the same period. The study measured new diagnoses of various disorders during the 5-year period following presentation. There were a total of 180 females and 102 males in the study. The mean ages of the control and subject group were 76 and 81.8, respectively. Of our twelve tested comorbidity types, patients that suffered a periocular trauma were more likely to develop heart failure (p=0.00244), dementia (p=0.00002), Alzheimer's disease (p=0.00087), and vascular disease (p=0.00037). Geriatric patients who sustained ocular and periocular injuries had a greater incidence of heart failure, dementia, Alzheimer's disease, and atherosclerosis diagnoses in the 5-year period following injury. The findings of this study suggest that periocular trauma may be an early indicator of underlying degenerative or systemic disease. Ophthalmologists should ensure proper primary care follow-up in conjunction with recovery from injury.

Clinical and instrumental features in 82 patients with insufficient sleep syndrome.

Insufficient sleep syndrome possibly represents the worldwide leading cause of daytime sleepiness, but remains poorly recognised and studied. The aim of this case series is to comprehensively describe a cohort of patients with insufficient sleep syndrome. Eighty-two patients were studied concerning demographic and socio-economic features, medical, psychiatric and sleep comorbidities, substance use, sleep symptoms, actigraphy, video-polysomnography, multiple sleep latency tests and treatment. The typical patient with insufficient sleep syndrome is a middle-aged adult (with no difference of gender), employed, who has a family, often carrying psychiatric and neurological comorbidities, in particular headache, anxiety and depression. Other sleep disorders, especially mild sleep apnea and bruxism, were common as well. Actigraphy was a valuable tool in the characterisation of insufficient sleep syndrome, showing a sleep restriction during weekdays, associated with a recovery rebound of night sleep during weekends and a high amount of daytime sleep. An over- or underestimation of sleeping was common, concerning both the duration of night sleep and daytime napping. The average daily sleep considering both daytime and night-time, weekdays and weekends corresponds to the recommended minimal normal duration, meaning that the burden of insufficient sleep syndrome could mainly depend on sleep fragmentation and low quality. Sleep efficiency was elevated both in actigraphy and video-polysomnography. Multiple sleep latency tests evidenced a tendency toward sleep-onset rapid eye movement periods. Our study offers a comprehensive characterisation of patients with insufficient sleep syndrome, and clarifies their sleeping pattern, opening avenues for management and treatment of the disorder. Current options seem not adapted, and in our opinion a cognitive-behavioural psychotherapy protocol should be developed.

General Anesthesia, Cognition, and Neurological Comorbidities

General anesthesia is a frequently employed medical intervention that facilitates the induction of a temporary state of unconsciousness, hence facilitating the execution of surgical procedures in patients. Nevertheless, the cognitive capabilities of patients with neurological comorbidities, such as epilepsy or dementia, may be a subject of worry when contemplating the impact of general anesthesia. Studies have indicated that individuals who have pre-existing neurological diseases may encounter negative consequences on their brain function when exposed to anesthesia. These consequences can manifest as a reduction in cognitive abilities or a worsening of their current coexisting medical conditions. Hence, it is imperative for healthcare practitioners to thoroughly assess the potential advantages and disadvantages of general anesthesia in individuals with neurological comorbidities. This evaluation should encompass exploring alternative methodologies or tailoring anesthetic management strategies to mitigate potential complications and enhance patients’ overall results.

Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England

PurposeBenign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients’ risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. MethodsWe retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. ResultsAcross ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6–8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2–16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2–12%). ConclusionsIn this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring.

Factors associated with tracheostomy decannulation in infants with bronchopulmonary dysplasia

ObjectivePremature infants represent a unique subset of patients who may require tracheostomy. Bronchopulmonary dysplasia (BPD) is among one of the most common sequelae of prematurity contributing to the need for prolonged ventilation requiring tracheostomy after other airway options have been exhausted. Our objective is to understand socioeconomic barriers to decannulation and identify factors that accelerate safe decannulation, focusing on patients with BPD. MethodsAn existing internal database from a tertiary pediatric hospital of patients undergoing tracheostomy prior to one year old was reviewed. Data from January 1, 2005 through December 31, 2020 was used to compare patients who were successfully decannulated to those who were not. A further subset of infants with BPD were identified and analyzed. Of those decannulated, survival analysis was used to identify factors associated with decreased time to decannulation. ResultsWe identified 303 infants who underwent tracheostomy at less than one year old with 125 of those infants having a diagnosis of BPD. Of the 125 infants with BPD, 44 (35.2 %) were decannulated and 81 (64.8 %) were not. There was no significant difference in sex, race, ethnicity, insurance status, comorbidities, or presence of syndromes between those patients with BPD who were decannulated and those who were not. Those who were not decannulated had a significantly longer length of hospital stay, prolonged ventilator requirements after tracheostomy, and were more likely to be discharged home on the ventilator (p = 0.030; 0.020; 0.002, respectively). Of the 44 decannulated patients, mean and median time to decannulation were 37.9 and 27.8 months respectively (range 10.8–160.6 months). There was an inverse association with decannulation and both Black race (HR: 0.30) and neurological comorbidity (HR: 0.37) on multivariate analysis. Black race, presence of syndrome, and length of ventilator dependence were significantly associated with increased time to decannulation. Time to decannulation from time off the ventilator was not significantly influenced by sex, race, ethnicity, state of residence, or insurance status, but was significantly influenced by age (95 % CI: −6.9, −0.1; P = 0.044). While time from discharge to first follow up visit did not significantly impact time to decannulation, every additional follow up visit increased time to decannulation by 3.78 months when adjusting for confounding variables. ConclusionIn infants with BPD under one year requiring tracheostomy, socioeconomic factors were not found to influence likelihood of decannulation, however Black race, presence of underlying syndrome, and increased length of ventilator dependence were associated with prolonged timing. Children with more frequent follow up visits similarly had an increased time to decannulation, illustrating a vital point in the process. Ventilator weaning protocols and standardized decannulation protocols in patients with BPD, along with caregiver education, can safely expedite and facilitate decannulation.

Ultra-fast deep-learned CNS tumour classification during surgery

Central nervous system tumours represent one of the most lethal cancer types, particularly among children1. Primary treatment includes neurosurgical resection of the tumour, in which a delicate balance must be struck between maximizing the extent of resection and minimizing risk of neurological damage and comorbidity2,3. However, surgeons have limited knowledge of the precise tumour type prior to surgery. Current standard practice relies on preoperative imaging and intraoperative histological analysis, but these are not always conclusive and occasionally wrong. Using rapid nanopore sequencing, a sparse methylation profile can be obtained during surgery4. Here we developed Sturgeon, a patient-agnostic transfer-learned neural network, to enable molecular subclassification of central nervous system tumours based on such sparse profiles. Sturgeon delivered an accurate diagnosis within 40 minutes after starting sequencing in 45 out of 50 retrospectively sequenced samples (abstaining from diagnosis of the other 5 samples). Furthermore, we demonstrated its applicability in real time during 25 surgeries, achieving a diagnostic turnaround time of less than 90 min. Of these, 18 (72%) diagnoses were correct and 7 did not reach the required confidence threshold. We conclude that machine-learned diagnosis based on low-cost intraoperative sequencing can assist neurosurgical decision-making, potentially preventing neurological comorbidity and avoiding additional surgeries.

Blood transfusions in non-major burns patients

BackgroundBlood transfusions are essential to treating anaemia of burn injuries. It has recently been observed that patients with non-major burns < 20%TBSA may also develop anaemia requiring transfusion of blood products. Due to the morbidity and mortality rate associated with blood transfusions better understanding of risk factors may guide clinical practices to improve patient care. ObjectiveTo determine risk factors for transfusion of blood products in patients with non-major burn injuries and assess transfusion practices to establish impact on patient outcome. MethodOur study included 182 adult patients with non-major burn injuries, < 20%TBSA admitted over a 3-year period at the Department of Plastic Surgery and Burns Unit of the Emergency County Hospital Cluj-Napoca. We analysed patient and injury characteristics: age, gender, %TBSA burn, %FT burn, burn site, mechanism of injury, inhalation injury, Hb lab determinations throughout admission and surgical management. Charlson comorbidities index has been determined based on cardiovascular, neurological, gastrointestinal and renal comorbidities as well as diabetes mellitus. We selected blood transfusions, wound infections and length of hospital stay as outcome for our analysis. Results37.9% of patients included in our study developed anaemia throughout admission and 7.7% underwent blood transfusions. Mean Hb levels triggering blood transfusions have been recorded at 7.4 (IQR=8.8–9.9) g/dL. Patients who received transfusions were older, presented with higher %TBSA and associated a higher comorbidity index. They also tended to develop coagulopathy and underwent more surgical procedures to achieve wound closure. In transfused patients who associate comorbidities we observed a higher rate of wound infections and longer hospital stay. ConclusionsPatient related comorbidities correlate with higher transfusion rates in non-major burn injuries. Due to the risk associated with the use of blood products decision to transfuse should adhere to current guideline practices and be tailored to specific patient requirements.

14 Comorbidities Affecting Children with Autism Spectrum Disorder: A Retrospective Chart Review from the Main Referral Site for ASD Evaluation in Manitoba

Abstract Background Autism Spectrum Disorder (ASD) is a developmental disorder characterized by deficits in social interaction/communication, restricted interests and repetitive behaviours. Recent discussions have emerged worldwide regarding a possible “overly-inclusive” diagnosis of ASD, adding heterogeneity around presentation/etiology and comorbidities. Objectives This study aimed to determine the frequency and characteristics of comorbidities among children diagnosed with ASD in Manitoba, and to evaluate differences in presentation between those with and without medical comorbidities. As comorbid neurodevelopmental disorders such as global developmental delay (GDD) and attention-deficit yyperactivity disorder (ADHD) are common in children with ASD, these were not included as “medical comorbidities” and were studied separately. Design/Methods We conducted a retrospective chart review of &amp;gt;2000 electronic charts at the main referral site for children &amp;lt;6 years requiring evaluation for ASD in Manitoba. All children aged 0-5 years diagnosed with ASD at this site between May 2016 to September 2021 were identified. X2 and t test were used to compare groups. Results Of the total of 1858 children identified, 1459 (78%) were male, 252 (13.5%) were born prematurely, 504 (27%) had ≥1 medical comorbidity. Most common medical comorbidities were neurological (12.7%) and allergies/eczema (6.1%). Comorbid GDD was diagnosed in 428 (23%). Age of referral to RCC and age of diagnosis did not differ between groups. Medical comorbidities were more common among preterm children (31% vs. 26%, p:&amp;lt;0.01) and children with comorbid GDD (35% vs. 18.6%, p:&amp;lt;0.01). There was no significant difference in overall presence of medical comorbidities by sex (29.5% vs. 26.6%, p: 0.25); however, girls had a statistically significant higher incidence of neurological comorbidities, e.g. cerebral palsy, epilepsy, hypotonia NYD (16% vs. 12%, p:0.03). Conclusion Results of this study are consistent with previous studies, which note high comorbidity rates among children with ASD. The high rates of associated neurological conditions, GDD, and prematurity add heterogeneity to this group and may relate to the reported “overly-inclusive” diagnosis. This study will be used as a catalyst for guiding further prospective studies in the area.

P07.15.B NEUROMUSCULAR HIGH-RESOLUTION ULTRASOUND IN PERIPHERAL NEUROTOXICITY OF SYSTEMICALLY TREATED CANCER PATIENTS

Abstract BACKGROUND Up to 40 % of cancer patients treated with neurotoxic cytostatic chemotherapies develop treatment-induced peripheral neuropathy. Furthermore, in patients treated with immune checkpoint inhibitors neuromuscular immune-related adverse events (irAEs) are the most common neurological complication. The differentiation between various types of peripheral neurotoxicity, neurological comorbidities and (para-)neoplastic conditions requires experienced clinical and neurophysiological diagnostics within an interdisciplinary team of experts. High-resolution ultrasound (HRUS) is a widely used diagnostic tool for peripheral neuropathies. As there are no generally approved biomarkers of treatment-related neurotoxicity so far, HRUS might extend the repertoire of diagnostic and neuromonitoring methods in patients with neuropathies induced by cytostatic agents, immunotherapy, and targeted therapy. MATERIAL AND METHODS We present the integration of HRUS into a standardized algorithm for suspected peripheral neurotoxicity by characterizing a case series from our neuro-oncological center. We show representative HRUS findings of seven cancer patients (diagnosed with breast cancer, cholangiocarcinoma, colorectal carcinoma, or multiple myeloma) treated with platinum derivates, immune checkpoint inhibitors, bortezomib, or lenalidomide. RESULTS We describe the potential of HRUS independently of a certain cancer treatment regimen and beyond that in patients with both neurological co-morbidities and concomitant neoplastic infiltration of the nervous system. In our retrospective cohort, HRUS revealed partly continuous and partly discontinuous nerve swelling as well as compression syndromes. Moreover, we detected enlargements of dorsal roots and vagus nerve in cancer patients with treatment-induced neuropathies for the first time. In addition, we identified significant discordance between clinical, electrophysiological and HRUS findings and discuss how peripheral neurotoxicity may be amenable to complementary HRUS assessment and neuromonitoring. CONCLUSION At our institution, neuromuscular ultrasound is an integral part of the interdisciplinary algorithm for peripheral neuropathies in systemically treated cancer patients. HRUS expands the neurological tool inventory for cancer patients and accelerates the differentiation of peripheral neurotoxicity, neurological comorbidities, and neoplastic affection of the nervous system in a non-invasive and cost-sparing manner. Our data may help to detect distinct patterns of nerve enlargement as new biomarkers of peripheral neurotoxicity. Thus, we employed our data to conduct a prospective, cross-sectional trial (PARTICIPATE), which has the potential to define the diagnostic relevance of HRUS for patients treated with agents affecting the PNS and its impact on cancer patient care.

Short- and long-term survival in patients over 90 years old undergoing pacemaker implantation.

In Italy, 12-month survival in the general population between 90 and 94 years old is 26%. In very old patients, the benefit of pacemaker implantation in terms of quality and duration of life is unclear. The aim of our study was to analyse clinical characteristics, outcome and factors associated with survival in patients at least 90 years old at the time of the first pacemaker implant. Clinical parameters, device characteristics, survival and predictors of outcome in patients at least 90 years old treated with a pacemaker in our centre in 2019-2020 were evaluated. Among the 554 patients undergoing pacemaker implantation in our centre during the study interval, 69 (12%) were at least 90 years old; a complete/advanced atrioventricular block was present in 65%. A cardiological comorbidity (excluding atrial fibrillation) was present in 22 patients (32%). Oncological, pulmonary and neurological comorbidities were present in 12 (17%), 19 (28%) and 32 (46%), respectively. Renal impairment was present in 25 patients (36%). After pacemaker implantation, a pneumothorax developed in two patients and lead dislodgment in one. During follow-up (median 17 months, interquartile range: 13-24), 32 patients died (46%), with a 12-month mortality probability of 24.6%. At multivariate analysis, the presence of oncological (hazard ratio (HR) 5.31; P < 0.001) and neurological (HR 6.44; P < 0.001) comorbidities was associated with mortality. Truncating the outcome at 6 months, renal impairment (HR 8.01; P = 0.003), anticoagulant therapy (HR 8.14; P = 0.003), oncological comorbidities (HR 14.1; P < 0.001) and left ventricular function (5% increase of left ventricular ejection fraction: HR 0.66; P < 0.001) were significantly associated with outcome. At our centre, patients at least 90 years old underwent pacemaker implantation mainly for advanced atrioventricular block. One-year survival was excellent, even better than expected in the general population.

Divergent neurodevelopmental profiles of very-low-birth-weight infants.

Advanced perinatal medicine has decreased the mortality rate of preterm infants. Long-term neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs) remain to be investigated. Participants were 124 VLBWIs who had in-hospital birth from 2007 to 2015. Perinatal information, developmental or intelligence quotient (DQ/IQ), and neurological comorbidities at ages 3 and 6 years were analyzed. Fifty-eight (47%) VLBWIs received neurodevelopmental assessments at ages 3 and 6 years. Among them, 15 (26%) showed DQ/IQ <75 at age 6 years. From age 3 to 6 years, 21 (36%) patients showed a decrease (≤-10), while 5 (9%) showed an increase (≥+10) in DQ/IQ scores. Eight (17%) with autism spectrum disorder or attention-deficit hyperactivity disorder (ASD/ADHD) showed split courses of DQ/IQ, including two with ≤-10 and one with +31 to their scores. On the other hand, all 7 VLBWIs with cerebral palsy showed DQ ≤35 at these ages. Magnetic resonance imaging detected severe brain lesions in 7 (47%) of those with DQ <75 and 1 (18%) with ASD/ADHD. VLBWIs show a broad spectrum of neurodevelopmental outcomes after 6 years. These divergent profiles also indicate that different risks contribute to the development of ASD/ADHD from those of cerebral palsy and epilepsy in VLBWIs. Very-low-birth-weight infants (VLBWIs) show divergent neurodevelopmental outcomes from age 3 to 6 years. A deep longitudinal study depicts the dynamic change in neurodevelopmental profiles of VLBWIs from age 3 to 6 years. Perinatal brain injury is associated with developmental delay, cerebral palsy and epilepsy, but not with ASD or ADHD at age 6 years.

Exploring Interactions Between Traumatic Brain Injury History and Gender on Medical Comorbidities in Military Veterans: An Epidemiological Analysis in the VA Million Veteran Program.

Epidemiological studies of medical comorbidities and possible gender differences associated with traumatic brain injury (TBI) are limited, especially among military veterans. The purpose of this study was to examine relationships between TBI history and a wide range of medical conditions in a large, national sample of veterans, and to explore interactions with gender. Participants of this cross-sectional epidemiological study included 491,604 veterans (9.9% TBI cases; 8.3% women) who enrolled in the VA Million Veteran Program (MVP). Outcomes of interest were medical comorbidities (i.e., neurological, mental health, circulatory, and other medical conditions) assessed using the MVP Baseline Survey, a self-report questionnaire. Logistic regression models adjusting for age and gender showed that veterans with TBI history consistently had significantly higher rates of medical comorbidities than controls, with the greatest differences observed across mental health (odds ratios [ORs] = 2.10-3.61) and neurological (ORs = 1.57-6.08) conditions. Similar patterns were found when evaluating men and women separately. Additionally, significant TBI-by-gender interactions were observed, particularly for mental health and neurological comorbidities, such that men with a history of TBI had greater odds of having several of these conditions than women with a history of TBI. These findings highlight the array of medical comorbidities experienced by veterans with a history of TBI, and illustrate that clinical outcomes differ for men and women with TBI history. Although these results are clinically informative, more research is needed to better understand the role of gender on health conditions in the context of TBI and how gender interacts with other social and cultural factors to influence clinical trajectories following TBI. Ultimately, understanding the biological, psychological, and social mechanisms underlying these comorbidities may help with tailoring TBI treatment by gender and improve quality of life for veterans with TBI history.