Neurological Comorbidities Research Articles

Comorbidities Affecting Children with Autism Spectrum Disorder: A Retrospective Chart Review.

Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction/communication, restricted interests, and repetitive behaviors. Recent discussions have emerged worldwide regarding the heterogeneity around presentation/etiology and comorbidities. 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. We conducted a retrospective chart review of >1900 electronic charts at the only publicly funded referral site for children ≤6 years requiring evaluation for ASD in Manitoba. All children aged 0-6 years diagnosed with ASD at this site between May 2016 and September 2021 were identified. χ2 and t-tests were used to compare groups. Of the total of 1858 children identified, 1452 (78.1%) were boys, 251 (13.5%) were prematurely born, and 539 (29.0%) had ≥1 medical comorbidity. Global developmental delay (GDD) was diagnosed in 428 (23.0%). The age of referral and diagnosis did not differ between groups. Comorbidities were more common among premature children (16.0% vs. 12.5%, p: 0.005) and children with comorbid GDD (34.9% vs. 18.2%, p < 0.001). Neurological comorbidities were most common (37.1%). No sex difference in the overall presence of comorbidities was found (boys = 77.1% vs. 78.5%, p: 0.518); however, girls had a higher incidence of neurological comorbidities, e.g., cerebral palsy, seizures, hypotonia (14.8% vs. 9.64%, p: 0.009), as well as genetic comorbidities (4.92% vs. 2.75%, p: 0.04). The high rates of associated neurological conditions, GDD, and prematurity add heterogeneity to this group leading to potential difficulties with prognosis and service allocation. Primary vs. secondary ASD can be a way of separating individuals based on relevant medical comorbidities.

Psychiatric and neurological manifestations in adults with Smith-Magenis syndrome: A scoping review.

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder caused by a 17p11.2 deletion or a pathogenic variant of the RAI1 gene, which lies within the 17p11.2 region. Various psychiatric and neurological disorders have been reported in SMS, with most literature focusing on children and adolescents. To provide an overview of the current knowledge on this topic in adults with SMS, we performed a comprehensive scoping review of the relevant literature. Our findings suggest that many manifestations that are common in childhood persist into adulthood. Neuropsychiatric manifestations in adults with SMS include intellectual disability, autism spectrum- and attention deficit hyperactivity disorder-related features, self-injurious and physical aggressive behaviors, sleep-wake disorders, and seizures. Findings of this review may facilitate optimization of management strategies in adults with SMS, and may guide future studies exploring late-onset psychiatric and neurological comorbidities in SMS.

Incidence of and Risk Factors for Fellow-Eye Involvement in Sturge-Weber Syndrome Children With Unilateral Glaucoma.

Among children with unilateral glaucoma associated with Sturge-Weber syndrome (SWS), 7 of 47 demonstrated involvement in the fellow eye, and that group had had earlier first-eye surgery relative to the noninvolvement group. The aim of this study was to determine the incidence of and risk factors for fellow-eye involvement in children with unilateral SWS-associated glaucoma. Children diagnosed with a unilateral facial port-wine stain and ipsilateral glaucoma before the age of 5 and followed up for at least 5 years were enrolled. The incidence rates of fellow-eye glaucoma involvement were estimated per 100 person-years, and factors associated with a higher incidence of fellow-eye involvement were investigated. A total of 47 children [24 (51.1%) girls] with unilateral SWS-associated glaucoma were included. All of them had facial port-wine stain involving ophthalmic division of the trigeminal nerve, and 18 (38.3%) had neurological comorbidities. The mean age at glaucoma diagnosis was 0.8±1.2 years [range, 0.08 (1mo)-4.0y]. Over a median follow-up of 8.4 years, glaucoma was diagnosed in the fellow eye of 7 of the children (14.9%; incidence rate of 1.8 per 100 person-years), 6 of whom were girls ( P =0.097) and 5 of whom were diagnosed before the age of 4 years ( P =0.508). The fellow-eye-involvement group showed significantly higher mean follow-up intraocular pressure in the fellow eye, older age at first-eye surgery (both P <0.005), and higher frequency of choroidal hemangioma both at first onset and in fellow eyes ( P =0.026 and 0.019, respectively). In this cohort of SWS children diagnosed with unilateral glaucoma, the risk of fellow-eye involvement was higher in girls, within the first 4 years, and in cases with choroidal hemangioma. The fellow-eye-involved children underwent surgery on the first eye earlier than those without fellow-eye involvement.

Neurological side effects and drug interactions of antiviral compounds against SARS-CoV-2.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), rapidly spread across the globe. Tremendous efforts have been mobilized to create effective antiviral treatment options to reduce the burden of the disease. This article summarizes the available knowledge about the antiviral drugs against SARS-CoV-2 from a neurologist's perspective. We summarize neurological aspects of antiviral compounds against SARS-CoV-2 with full, conditional, or previous marketing authorization by the European Medicines Agency (EMA). Nirmatrelvir/ritonavir targets the SARS-CoV-2 3c-like protease using combinatorial chemistry. Nirmatrelvir/ritonavir levels are affected by medications metabolized by or inducing CYP3A4, including those used in neurological diseases. Dysgeusia with a bitter or metallic taste is a common side effect of nirmatrelvir/ritonavir. Molnupiravir is a nucleotide analog developed to inhibit the replication of viruses. No clinically significant interactions with other drugs have been identified, and no specific considerations for people with neurological comorbidity are required. In the meantime, inconsistent results from clinical trials regarding efficacy have led to the withdrawal of marketing authorization by the EMA. Remdesivir is a viral RNA polymerase inhibitor and interferes with the production of viral RNA. The most common side effect in patients with COVID-19 is nausea. Remdesivir is a substrate for CYP3A4. Neurological side effects and drug interactions must be considered for antiviral compounds against SARS-CoV-2. Further studies are required to better evaluate their efficacy and adverse events in patients with concomitant neurological diseases. Moreover, evidence from real-world studies will complement the current knowledge.

Niacin modulates depressive-like behavior in experimental colitis through GPR109A-dependent mechanisms

AimsDepression is one of the common neurological comorbidities in patients with inflammatory bowel disease (IBD). The current study aimed to investigate the potential impact of niacin on colitis-induced depressive-like behavior in rats. Materials and methodsAnimals were given 5 % dextran sulfate sodium (DSS) in drinking water for one week to induce colitis. Niacin (80 mg/kg), with or without mepenzolate bromide (GPR109A blocker), was administered once per day throughout the experimental period. Rats were tested for behavioral changes using open field and forced swimming tests. Key findingsNiacin significantly ameliorated DSS–induced behavioral deficits and alleviated macroscopic and microscopic colonic inflammatory changes. It also augmented the hippocampal levels of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the blood-brain barrier (BBB) integrity. Moreover, niacin decreased hippocampal IL-1ꞵ and NF-ĸB contents but increased GSH, Sirt-1, Nrf-2, HO-1 concentrations. All these beneficial effects were partially abolished by the co-administration of mepenzolate bromide. SignificanceThe neuroprotective effect of niacin against DSS-induced depressive-like behavior was partially mediated through GPR109A-mediated mechanisms. Such mechanisms are also involved in modulating neuronal oxidative stress and inflammation via Sirt-1/Nrf-2/HO-1 signaling pathways.

Neurological comorbidities and novel mutations in Turkish cases with neurofibromatosis type 1.

<p>Neuro&shy;fibromatosis type 1 (NF1) is a rare, auto&shy;somal dominant multisystemic disease. The NF1 gene is localized on chromosome 17q11.2. Patients with NF1 have different clinical presentations and comorbidities. The aim of the present study is to determine the novel mutations and neurological comorbidities of NF1.</p>. <p>Patients who were diagnosed with NF1 by clinical criteria of the National Institutes of Health were included in the study. After a detailed examination, the NF1 gene was analysed with the help of next generation sequencing technology from pe&shy;ripheral blood samples via MiSeq (Illu&shy;mina, USA). Bioinformatic analyzes were per&shy;for&shy;med to evaluate the clinical sig&shy;ni&shy;fi&shy;cance of the detected variants via the in&shy;ternational databanks in accordance with the ACMG (American College of Medical Ge&shy;netics) guide&shy;line. In addition, cerebral-spinal MRI, cerebral angiography, and ENMG exa&shy;mi&shy;na&shy;tions were performed if deemed necessary.</p>. <p>Twenty patients (12 female, 8 male) were included in the study. The mean age was 25.8&plusmn;10 (10-56) years. Previously defined 13 different pathogenic mutations according to the ACMG criteria were identified in 18 patients. Also, two novel mutations were detected in 2 cases. Moreover, neurological comorbidities (moyamoya disease, multiple sclerosis, Charcot Marie Tooth Type 1A) were found in 3 patients with NF1.</p>. <p>In the present study two novel mutations and three different neurological comorbidities were identified in NF1.</p>.

The Neuropsychiatric Safety Profile of Lasmiditan: A Comparative Disproportionality Analysis with Triptans.

Migraine constitutes the world's second-leading cause of disability. Triptans, as serotonin 5-HT1B/1D receptor agonists, remain the first-line treatment, despite discouraged use in individuals at high cardiovascular risk. Lasmiditan, a selective lipophilic 5-HT1F agonist without vasoconstrictive effects, is an emerging option. We aimed to investigate the safety profile of lasmiditan in the WHO pharmacovigilance database (VigiBase®) using a comparative disproportionality analysis with triptans. VigiBase® was queried for all reports involving lasmiditan and triptans. Disproportionality analyses relied on the calculation of the information component (IC), for which 95% confidence interval (CI) lower bound positivity was required for signal detection. We obtained 826 reports involving lasmiditan. Overall, 10 adverse drug reaction classes were disproportionately reported with triptans, while only neurological (IC 1.6; 95% CI 1.5-1.7) and psychiatric (IC 1.5; 95% CI 1.3-1.7) disorders were disproportionately reported with lasmiditan. Sedation, serotonin syndrome, euphoric mood, and autoscopy had the strongest signals. When compared with triptans, 19 out of 22 neuropsychiatric signals persisted. The results of our analysis provide a more precise semiology of the neuropsychiatric effects of lasmiditan, with symptoms such as autoscopy and panic attacks. The cardiovascular adverse drug reaction risk with triptans was confirmed. In contrast, caution is warranted with lasmiditan use in patients with neurological or psychiatric comorbidities or serotonin syndrome risk. Our study was hindered by pharmacovigilance flaws, and further studies should help in validating these results. Our findings suggest that lasmiditan is a safe alternative for migraine treatment, especially when the neuropsychiatric risk is outweighed by the cardiovascular burden.

Association of age with death and withdrawal of life-sustaining therapy after severe traumatic brain injury.

Compared to younger age, older age (≥ 65 yr) is associated with worse outcomes after severe traumatic brain injury (TBI). We sought to describe the association of older age with in-hospital death and aggressiveness of intervention. We conducted a retrospective cohort study of adult (age ≥ 16 yr) patients with severe TBI admitted to a single academic tertiary care neurotrauma centre between January 2014 and December 2015. We collected data through chart review as well as from our institutional administrative database. We provided descriptive statistics and used multivariable logistic regression to evaluate the independent association of age with the primary outcome, in-hospital death. The secondary outcome was early withdrawal of life-sustaining therapy. There were 126 adult patients (median age 67 yr [Q1-Q3, 33-80 yr]) with severe TBI during the study period who met our eligibility criteria. The most common mechanism was high-velocity blunt injury (55 patients [43.6%]). The median Marshall score was 4 (Q1-Q3, 2-6), and the median Injury Severity Score was 26 (Q1-Q3, 25-35). After controlling for confounders including clinical frailty, pre-existing comorbidity, injury severity, Marshall score and neurologic examination at admission, we observed that older patients were more likely than younger patients to die in hospital (odds ratio 5.10, 95% confidence interval 1.65-15.78). Older patients were also more likely to experience early withdrawal of life-sustaining therapy and less likely to receive invasive interventions. After controlling for confounding factors relevant to older patients, we observed that age was an important and independent predictor of in-hospital death and early withdrawal of life-sustaining therapy. The mechanism by which age influences clinical decision-making independent of global and neurologic injury severity, clinical frailty and comorbidities remains unclear.

Psychometric properties of the Mongolian version of the Pittsburgh Sleep Quality Index

Poor sleep quality is associated with decreased brain health, such as fatigue, low quality of life, and risk of neurological and psychiatric comorbidities. Until now, no testing instruments for an accurate assessment of sleep quality for use in the general population have been rigorously translated and validated in Mongolia. We aimed to determine the psychometric properties of the globally recognized screening tool and sleep quality in the general population of Mongolia. In this cross-sectional study, participants were randomly selected between August and October 2020, from 64 sites in 8 urban, and 9 rural areas in Mongolia. Of the total 1152 participants (mean age, SD=42.66±12.6, range: 18 and 65) 76% were women. An overall Cronbach’s α was 0.69. Both EFA and CFA indicated a two-factor solution. The PSQI total score was positively correlated with anxiety and depression. The PSQI total score (p values &lt; 0.01) was negatively correlated with the mean scores of all domains of WHOQOL-BREF. The mean PSQI total score was 5.67±3.4 and 43% of the participants were classified as poor sleepers by a global cut-off point of 5. The Mongolian version of the PSQI demonstrated a reliable and valid tool for screening sleep quality among the Mongolian general population. The results suggest that the prevalence rate of poor sleep quality was 43% using PSQI global cut-off point.

Guillain-Barre Syndrome Mimicked by Spinal Stenosis in A Case of Chronic Prolapsed Intervertebral Disc: A Case Report

Background: Guillain-Barre Syndrome (GBS) is a rare acute autoimmune polyneuropathy, usually preceded by infections. It can be difficult to diagnose, especially in patients with underlying neurological comorbidities. Case: A 54-year-old male, with a long history of a prolapsed intervertebral disc, presented with progressive and asymmetrical onset tetraparesthesia for 4 weeks, which was associated with progressive paraparesis for 2 weeks. The diagnosis of GBS was initially missed due to a lack of relevant history of prior infection, atypical presentation (asymmetrical limb weakness), and radiological evidence of spinal stenosis. Nerve conduction study, cerebrospinal fluid analysis, and antiganglioside antibodies later confirmed the diagnosis of GBS. The patient was started on intravenous immunoglobulin and achieved significant improvement. He was discharged a week later and transferred to a rehabilitation hospital. Conclusion: GBS should not be excluded prior to diagnostic tests and lab work in neurological patients. Physicians should avoid over-reliance on radiological findings to conclude a diagnosis. Comprehensive history and examinations to understand the development of patients' presentations should be prioritized when establishing a diagnosis.

Intravenous Drug Use‐Associated Endocarditis Leads to Increased Intracranial Hemorrhage and Neurological Comorbidities

Background The United States is experiencing a rapidly increasing rate of opioid drug abuse. Intravenous drug use (IVDU)‐related endocarditis can lead to significant neurological complications with high morbidity and mortality. When patient care necessitates anticoagulation, the standards for radiographic screening and the risk for intracranial hemorrhage are not clearly elucidated. Methods We conducted a retrospective cohort study involving patients treated for infective endocarditis at a single institution from 2014 to 2018. Patients were grouped based in history of IVDU and their demographics and clinical predictors for intracranial hemorrhage were analyzed. Results A total of 351 patients met inclusion criteria for this study, of whom 170 patients (48%) had a history of IVDU‐associated endocarditis. IVDU was associated with an increased prevalence of intracranial hemorrhage (25.9% versus 13.9%; P =0.005), including intraparenchymal hemorrhage (12.4% versus 5.1%; P =0.012), subarachnoid hemorrhage (17.6 versus 4.4%; P =0.001), and cerebral microbleeds (14.1% versus 7.2%; P =0.022). IVDU was also associated with an increased incidence of infectious intracranial aneurysm (10.6% versus 1.8%; P =0.001) and brain abscesses (4.7% versus 1.1%; P =0.025). Multivariate analysis showed that the presence of intracranial septic emboli (odds ratio [OR], 18.47 [8.4–40.250]; P =0.001) and infectious intracranial aneurysm (OR, 12.38 [3.24–47.28]; P =0.001) as significant predictive factors for intracranial hemorrhage after presenting with endocarditis. Conclusion The opioid epidemic has increased the incidence of infective endocarditis and resultant neurovascular complications. IVDU‐associated endocarditis is associated with increased hemorrhagic stroke and more frequent neurodiagnostic imaging.

Neuropsychiatric lupus in late- and early-onset systemic lupus erythematosus patients: a systematic review and meta-analysis.

Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients. A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959-2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I2 statistics. A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004). Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group.

Development of a Medical Complexity Score for Pediatric Aerodigestive Patients

To develop a complexity scoring system to characterize the diverse population served in pediatric aerodigestive clinics and help predict their treatment outcomes. A 7-point medical complexity score was developed through an iterative group consensus of relative stakeholders to capture the spectrum of comorbidities among the aerodigestive population. One point was assigned for each comorbid diagnosis in the following categories: airway anomaly, neurologic, cardiac, respiratory, gastrointestinal, genetic diagnoses, and prematurity. A retrospective chart review was conducted of patients seen in the aerodigestive clinic who had ≥2 visits between 2017 and 2021. The predictive value of the complexity score for the selected outcome of feeding progression among children with dysphagia was analyzed with univariate and multivariable logistic regression. We analyzed 234 patients with complexity scores assigned, showing a normal distribution (Shapiro Wilk P=.406) of the scores 1-7 (median,4; mean, 3.50 ± 1.47). In children with dysphagia, there was waning success in the improvement of oral feeding with increasing complexity scores (OR,0.66; 95% CI, 0.51-0.84; P=.001). Tube-fed children with higher complexity scores were incrementally less likely to achieve full oral diet (OR,0.60; 95% CI, 0.40-0.89; P=.01). On multivariable analysis, neurologic comorbidity (OR, 0.26; P<.001) and airway malformation (OR, 0.35; P=.01) were associated with a decreased likelihood to improve in oral feeding. We propose a novel complexity score for the pediatric aerodigestive population that is easy to use, successfully stratifies diverse presentations, and shows promise as a predictive tool to assist in counseling and resource use.

Incidence and characterization of neurological adverse events among a retrospective cohort of patients receiving immune checkpoint inhibitors.

2655 Background: The rising usage of immune checkpoint inhibitors (ICIs) has increased the incidence of rare adverse events in routine practice. Neurological adverse events (nAEs) are a heterogeneous group of outcomes that are infrequent and typically diagnosed by exclusion. They more often involve the peripheral (e.g., neuropathy, myasthenia gravis) than the central nervous system (e.g., encephalitis, hypophysitis). Evidence remains extremely limited with no large cohorts and incidence reported through small case series. This study aimed to analyze data from all clinically significant nAEs to characterize their risk factors, incidence, severity, and management. Methods: We created a retrospective registry of all patients who received at least one dose of an ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. Study personnel reviewed clinical documentation from all patients to collect data on treatment-emergent adverse events; attribution and severity were estimated using National Cancer Institute guidelines and the Common Terminology Criteria for Adverse Events. The investigators created a secure, cloud-based registry (REDCap), validated it with data quality rules, and resolved all discrepancies; clinical research specialists at Vasta Global captured most of the data. Categorical variables were compared using Fisher’s exact test. Statistical significance defined as p &lt; 0.05. The study had institutional IRB approval. Results: In the total cohort of 3,137 patients, there were 47 nAEs (1.49%). The majority of these nAEs were peripheral (31, 0.99%; grade 3/4 in 14 patients, 0.45%) as opposed to central (16, 0.50%; grade 3/4 in 8, 0.25%). Pre-existing neurological comorbidities were present in five patients who had central nAEs (stroke = 3, dementia = 2) and in one patient with a peripheral nAE (stroke = 1). All high-grade (3-4) central nAEs occurred among renal (4, 50%), melanoma (3, 38%), or lung (1, 12.5%) primaries which was statistically significant when compared to other grade 3/4 adverse events (p &lt; 0.0001) or no adverse events (p &lt; 0.0001). Median days from first ICI to nAE was 55 IQR [22-175] and average treatment with prednisone equivalent was 2.5 mg/kg, std 4.6. Conclusions: The incidence of nAEs (1-2%) appeared higher than prior estimates in this retrospective patient registry which included patients who did not have neurology consultation or specific billing codes. All high-grade nAEs occurred in a tumor type known to favor metastases to the brain. With similar patterns among low grade events, an underlying mechanism of molecular mimicry seems more likely. Both time to presentation and treatment remained highly heterogenous. Further research is needed on treatment-emergent nAEs to determine if they are potentiated by neurologic comorbidities or subclinical brain metastases.

Neurological and psychiatric comorbidities of migraine: Concepts and future perspectives.

This narrative review aims to discuss several common neurological and psychiatric disorders that show comorbidity with migraine. Not only can we gain pathophysiological insights by studying these disorders, comorbidities also have important implications for treating migraine patients in clinical practice. A literature search on PubMed and Embase was conducted with the keywords "comorbidity", "migraine disorders", "migraine with aura", "migraine without aura", "depression", "depressive disorders", "epilepsy", "stroke", "patent foramen ovale", "sleep wake disorders", "restless legs syndrome", "genetics", "therapeutics". Several common neurological and psychiatric disorders show comorbidity with migraine. Major depression and migraine show bidirectional causality and have shared genetic factors. Dysregulation of both hypothalamic and thalamic pathways have been implicated as a possibly cause. The increased risk of ischaemic stroke in migraine likely involves spreading depolarizations. Epilepsy is not only bidirectionally related to migraine, but is also co-occurring in monogenic migraine syndromes. Neuronal hyperexcitability is an important overlapping mechanism between these conditions. Hypothalamic dysfunction is suggested as the underlying mechanism for comorbidity between sleep disorders and migraine and might explain altered circadian timing in migraine. These comorbid conditions in migraine with distinct pathophysiological mechanisms have important implications for best treatment choices and may provide clues for future approaches.

Hypoxia-induced factor-1α and markers of inflammation in patients with ischemic stroke

Ischemic stroke (IS) occurs as a result of local disturbance of hemocirculation and hypoxia in the brain tissue. Hypoxia-inducible factor-1α (HIF-1α), which is involved in the regulation of tissue oxygen levels, plays an important role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, blood-brain barrier permeability, and is important in IS outcomes. The purpose of the study was to determine the relationship between blood levels of HIF-1α and the degree of neurological deficit in the acute period of IS and the outcome of the disease. We examined 58 people with IS aged 73 (67-81) years. Patients were divided into two groups – discharged and dead. The severity of stroke (NIHSS), neurological deficit, comorbidity index, blood levels of HIF-1α, p53 protein, interleukin-6, cystatin C, CRP, creatinine, hematological parameters were determined at admission, on days 3 and 10 of the disease. At admission the blood levels of HIF-1α was lower than in the comparison group and remained reduced until the 10th day. On day 10 the association of HIF-1α with neurological deficit, comorbidity index and disease outcome was determined. We observed a feedback of HIF-1α with the content of erythrocytes, hemoglobin and hematocrit, which can be regarded as a reflection of the hemic component of mixed hypoxia. In dead patients, an increased blood level of cystatin C was detected, which was associated with HIF-1α concentrations. In all periods of observation of IS, a correlation between cystatin C and creatinine and CRP levels was noted. These results may indicate dysfunction of endotheliocytes, inflammation associated with hypoxia in IS. The prognostic significance of the blood level of HIF-1α on the 10th day for the outcome of IS was AUC = 0.900. Blood levels of HIF-1α in the acute period was associated with the severity of IS and the outcome of the disease.

Prevalence of Concomitant Neurological Disorders and Long-Term Outcome of Patients Hospitalized for Intracerebral Hemorrhage with Versus without Cerebral Amyloid Angiopathy.

Patients with intracerebral hemorrhage (ICH) related to cerebral amyloid angiopathy (CAA) are at increased risk of developing epilepsy and cognitive disorders such as Alzheimer's disease (AD), mild cognitive impairment (MCI), and vascular dementia. In a retrospective cohort observation study of patients hospitalized for ICH with CAA versus ICH without CAA, we evaluated the prevalence of neurological comorbidities at admission and the risk of new diagnosis of epilepsy, relevant cognitive disorders, and mortality at 1year. In the TriNetX health research network, adult patients aged ≥ 55years hospitalized with a diagnosis of ICH were stratified based on presence or absence of concomitant CAA diagnosis. Demographics and medical comorbidities were compared by using χ2 test and Student's t-test. After 1:1 propensity score matching, 1-year survival was assessed with Kaplan-Meier curves. The 1-year risk of new diagnosis of epilepsy, AD, MCI, vascular dementia, and dementia unspecified was assessed with Cox proportional hazards estimate. The study included a total of 1757 patients with ICH and CAA and 53,364 patients with ICH without CAA.Patients with CAA were older compared with those without CAA (74.1 ± 7.5 vs. 69.8 ± 8.8years, p ≤ 0.001). Compared with ICH without CAA, patients with ICH and CAA had higher baseline prevalence of cerebral infarction (30% vs. 20%), nontraumatic ICH (36% vs. 7%), nontraumatic subarachnoid hemorrhage (14% vs. 5%), epilepsy (11% vs. 6%), and AD (5% vs. 2%) with significance at p < 0.001. After propensity score matching, a total of 1746 patients were included in both cohorts. In the matched cohorts, compared with patients with ICH without CAA, patients with ICH and CAA had lower 1-year all-cause mortality (479 [27%] vs. 563 [32%]; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.71-0.90) and higher risk of new diagnosis of epilepsy (280 [18%] vs. 167 [11%]; HR 1.70; 95% CI 1.40-2.06), AD (101 [6%] vs. 38 [2%]; HR 2.62; 95% CI 1.80-3.80), MCI (85 [5%] vs. 35 [2%]; HR 2.39; 95% CI 1.61-3.54), vascular dementia (117 [7%] vs. 60 [4%]; HR 1.92; 95% CI 1.41-2.62), and dementia unspecified (245 [16%] vs. 150 [9%]; HR 1.70; 95% CI 1.39-2.08). Among patients admitted for ICH, patients with CAA have lower mortality but have 2-3 times more risk of diagnosis of epilepsy and dementia at 1year, compared with those without CAA.

0118 Association between TNF-α G308A Polymorphism (rs1800629) and Insomnia Vulnerability in Fertile Age Women with Primary Dysmenorrhea

Abstract Introduction Higher tumor necrosis factor-alpha (TNF-α) gene expression has been revealed in the peripheral blood monocytes across the menstrual cycle in patients with primary dysmenorrhea (PDM) than in the unaffected control. Sleep quality is affected by environmental factors, endocrine function abnormalities and genetic factors. The aim of this study was to evaluate the effect of TNF-α G308A polymorphism (rs1800629) on the self-reported sleep, health, menstrual pain severity as well as peri-ovulatory serum TNF-α level in women with and without PDM. Methods Sleep, psychological and physiological characteristics and menstrual pain severity were collected with questionnaires and sleep/menstrual diary within a menstrual cycle from a cohort of 43 PDM women and 42 healthy controls (aged 20-30 years, right-handed, non-smoking and non-shift workers without psychiatric, sleep and neurological comorbidity). Chi-square tests were used to check if the genotype proportions of the investigated gene fitted the Hardy-Weinberg equilibrium (HWE) and to evaluate if the genotypic and allelic distribution is associated with PDM. Chi-square tests or analysis of variance were used to examine the effects of genotype, group and/or genotype x group interaction with the sleep, mind and the body health variables. Results Neither allele frequencies nor genotypes of TNF-α G-308A gene could serve as an independent risk factor of PDM in the Taiwanese population. Circulating serum TNF-α did not correspond with the -308 TNF-α promoter polymorphism, either, which might be due to a multifactorial control process. The TNF-α 308 A allele carriers (28.6%) which was less common than the G allele carriers (71.4%), showed lower Beck depression score, lower bodily pain and better physical health and higher subjective sleep quality. Furthermore, in G allele carriers, the PDM group showed higher insomnia severity and lower sleep duration than that of the control group. Conclusion Present results suggested that TNF-alpha polymorphism conferred no prediction to PDM risk and peri-ovulatory serum TNF-α level. However, our findings were evident that the A allele at the TNFα 308 locus, as compared to the more common G allele, was associated to better health and better sleep, with an indication of a genetic underpinning to their better resistance from the risk of PDM. Support (if any)

Neurologic Manifestation in Children with Coronavirus Disease 2019 at Prof. Dr. I.G.N.G Ngoerah Tertiary Hospital

AIM: The objective of the study is to describe neurologic manifestation in children with coronavirus disease-2019 (COVID-19) at Prof. Dr. I.G.N.G Ngoerah Hospital. METHODS: This was a retrospective descriptive study using the medical record with a total sampling of children with confirmed COVID-19 that manifests neurologic symptoms. Exclusion criteria were pre-existing neurologic comorbidities and incomplete medical records. RESULTS: From March 2020 to December 2021, from 308 children with confirmed cases of COVID-19, 106 had neurologic symptoms, 17 were excluded (16 pre-existing comorbidities, and 1 incomplete medical record), and total samples were 89 (28.8%) from inpatient and outpatient. Most children were male (57.3%) with a median age of 13 years. Most symptoms found were anosmia (73%), followed by a decrease in consciousness (19.1%) and seizure (10.1%). Children with anosmia median age were 14 years. There were 84 (94.3%) children with specific neurological symptoms (encephalopathy, seizures, and anosmia) and 5 (5.7%) with non-specific neurological symptoms (headache). CONCLUSION: There were 28.8% confirmed cases of COVID-19 with a neurologic manifestation, and most symptoms found were anosmia (73%).

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

Abstract Funding Acknowledgements Type of funding sources: None. Background According to the Italian National Statistical Institute, the 12-month probability of survival in the 90-94 years-old general population is 26%. In very old patients (pts) the benefit of pacemaker (PM) implantation in terms of quality and duration of life is unclear and could be considered futile. Purpose To analyze clinical characteristics, outcome and factors associated with survival in pts who had turned 90 at the time of the first PM implant. Methods All the PM implants performed in our Centre from 1/1/2019 to 1/31/2020 in pts ≥90 year-old at the time of the procedure were analyzed. Clinical parameters, device characteristics and follow-up data until 31/3/2022 were extrapolated from the SuitEstensa Ebit reporting system; the exitus was verified by analyzing data from the Regional Health System. Results During the study interval, among the 554 pts undergoing PM implantation in our Center, 69 (12%) were ≥90 years-old at the date of implantation (mean age 92±2 years, 46% male; complete/advanced AV block in 76%). Twenty-six (38%) pts had history of atrial fibrillation and 19 (28%) ischemic heart disease. A cardiological co-morbidity (excluding AF) was present in 23 pts (33%). Oncological, pneumological and neurological comorbidities were present in 12 (18%), 19 (28%) and 32 (46%) respectively. Renal impairment was present in 25 pts (36%). In 47 pts (68%) at least 2 co-morbidities were present. After implantation (VVIR in 36, DDDR in 25 and VDD in 8 patients) a pneumothorax developed in 2 pts and lead dislodgment in 1. Remote monitoring was activated in 57 pts (83%). Within 31/3/2022 (median follow-up 17 months, IQR: 13-24) 33 pts died (37%, in median 12 months after implant, IQR: 3-16), with 12-month survival probability of 75.4% (95% CI: 65.9-86.2). According to the Regional Health System database, no pts died for cardiac reason or device malfunction. Three pts died because of COVID-19 pneumonia. Renal dysfunction (Hazard Ratio-HR 2.64, p=0.006), the presence of 2 or more co-morbidities (HR 6.19; p= 0.003), diabetes (HR 2.53; p=0.009), ejection fraction (HR 0.88 for a difference of 5%; p=0.035), walking impairment (HR 3.64, p&amp;lt;0.001), the presence of oncological (HR 2.62; p=0.019), pneumological (HR 2.05; p=0.049), neurological (HR 4.57, p&amp;lt;0.001) and cardiovascular (HR: 2.20; p=0.015) comorbidities were associated with a higher risk of death at univariate analysis. Presence of oncological and neurological comorbidities were significant at multivariable analysis. Moreover, truncating the outcome at 6 months, renal dysfunction, anticoagulant therapy and ischemic disease were associated with short-term mortality. Conclusions At our Center, pts over the age of ninety undergo PM implantation mainly for advanced AVB. The good survival does not seem to justify particularly conservative attitudes, in the presence of clear indications for the implantation of the PM.