Severe Neurological Impairment Research Articles

Tracheostomy Placement in Severe Neurologic Impairment: Ethical Considerations and Provider Perspectives

Tracheostomy Placement in Severe Neurologic Impairment: Ethical Considerations and Provider Perspectives

Connecting Residents and Children with Severe Neurologic Impairment Using a Novel Personal History Tool

Connecting Residents and Children with Severe Neurologic Impairment Using a Novel Personal History Tool

Visceral Hyperalgesia in a Pediatric Palliative Care Patient without Severe Neurologic Impairment

Visceral Hyperalgesia in a Pediatric Palliative Care Patient without Severe Neurologic Impairment

VX‐765 alleviates motor and cognitive impairments via inhibiting PANoptosis activation in the neonatal rats after hypoxic–ischemic brain damage

AbstractNeonatal hypoxia–ischemia (HI) is one of the main factors that cause neonatal severe neurologic impairment and death. Shown by a large number of studies, caspase‐1 plays a significant effect in diseases such as hypoxic–ischemic brain damage (HIBD) and may be a key component of the protein complex that initiates PANoptosis. VX‐765, an inhibitor of caspase‐1, exerts a potential neuroprotective effect in traumatic brain injury. However, it is unknown whether the administration of VX‐765 has neuroprotective effects on neonatal rats that suffered HIBD, and if so, the underlying mechanisms are also still unknown. In the present study, we found that treatment with VX‐765 (50 mg/kg, i.p.) significantly ameliorated the impairment of locomotor coordination functions and myodynamia as well as the spatial learning and memory in neonatal rats subjected with HIBD. These behavior improvements were attributed to VX‐765 reducing infarct volumes and neuronal loss in the CA1, CA3 region of hippocampus, and deeper layers of the cortex in HIBD rats. Moreover, the enzyme‐linked immunosorbent assay showed that VX‐765 obviously decreased the production of neuroinflammatory factors including TNF‐α, IL‐1β, and IL‐6. Importantly, we identified HI promoted PANoptosis activation in vivo and in vitro, and VX‐765 obviously suppressed PANoptosis activation. Finally, we demonstrated that VX‐765 treatment reversed neuronal injury induced by oxygen–glucose deprivation (OGD). Taken together, these results suggest that VX‐765 protects the neurons against damage by suppressing neuroinflammation and PANoptosis activation, thereby improving locomotor coordination and cognitive impairments in neonatal HIBD rats, indicating that VX‐765 may be an underlying therapeutic drug for the clinical treatment of hypoxic–ischemic encephalopathy (HIE).

Biallelic Variants of MRPS36 Cause a New Form of Leigh Syndrome.

The MRPS36 gene encodes a recently identified component of the 2-oxoglutarate dehydrogenase complex (OGDHC), a key enzyme of the Krebs cycle catalyzing the oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. Defective OGDHC activity causes a clinically variable metabolic disorder characterized by global developmental delay, severe neurological impairment, liver failure, and early-onset lactic acidosis. We investigated the molecular cause underlying Leigh syndrome with bilateral striatal necrosis in two siblings through exome sequencing. Functional studies included measurement of the OGDHC enzymatic activity and MRPS36 mRNA levels in fibroblasts, assessment of protein stability in transfected cells, and structural analysis. A literature review was performed to define the etiological and phenotypic spectrum of OGDHC deficiency. In the two affected brothers, exome sequencing identified a homozygous nonsense variant (c.283G>T, p.Glu95*) of MRPS36. The variant did not affect transcript processing and stability, nor protein levels, but resulted in a shorter protein lacking nine residues that contribute to the structural and functional organization of the OGDHC complex. OGDHC enzymatic activity was significantly reduced. The review of previously reported cases of OGDHC deficiency supports the association of this enzymatic defect with Leigh phenotypic spectrum and early-onset movement disorder. Slightly elevated plasma levels of glutamate and glutamine were observed in our and literature patients with OGDHC defect. Our findings point to MRPS36 as a new disease gene implicated in Leigh syndrome. The slight elevation of plasma levels of glutamate and glutamine observed in patients with OGDHC deficiency represents a candidate metabolic signature of this neurometabolic disorder. © 2024 International Parkinson and Movement Disorder Society.

Drowning and Nonfatal Drowning in Children and Adolescents: A Subsequent Retrospective Data Analysis.

Fatal and nonfatal drowning are among the leading causes of death and lifelong severe neurological impairment among children and adolescents. This study aimed to complement research from Leipzig 1994-2008 to seek trends within risk factors, treatments, and outcomes throughout the last decade. We retrospectively investigated data of 47 inpatients aged 0-18 admitted to Leipzig University Department of Pediatrics who matched ICD-10 code T75.1 from 2008 to 2020 and compared them to a preceding study at the same institution. We also examined the prognostic value of parameters regarding the patients' outcomes. There were three median incidents per annum. The median age was 2.75 years; 76% of incidents happened in males. An accumulation was seen during the summer months and weekends. Most drowning incidents occurred in private ponds or pools (48.9%). Thirty-nine children were discharged without resulting morbidity, four showed neurological impairment, and three died. Risk factors concerning age, sex, and incident characteristics were confirmed. Special supervision needs still apply to 1-3-year-old male children or children with pre-existing health conditions around private pools and ponds. Hospitalization duration shortened, and morbidity and lethality decreased since the previous study. There was structural improvement in primary care and medical documentation. Parameters suggesting good outcomes include a submersion time < 5 min, GCS > 3 points, spontaneous movement upon admission, remaining pupillary light response, the absence of cardiovascular arrest, body temperature ≥ 32 °C, pH > 7, blood glucose < 15 mmol/L, lactate < 14 mmol/L, base excess ≥ -15 mmol/L, and the absence of ARDS. Clear legislation can contribute to improved private home water safety. Further studies should include a broad in- and outpatient spectrum and standardized incident documentation presupposing Utstein-style reporting. Regular reinvestigation of consistent geographical regions facilitates process evaluations of drowning epidemiology and therapy evolution.

Glucose phosphate isomerase deficiency demasked by whole-genome sequencing: a case report

BackgroundGlucose-6-phosphate isomerase deficiency is a rare genetic disorder causing hereditary nonspherocytic hemolytic anemia. It is the second most common glycolytic enzymopathy in red blood cells. About 90 cases are reported worldwide, with symptoms including chronic hemolytic anemia, jaundice, splenomegaly, gallstones, cholecystitis, and in severe cases, neurological impairments, hydrops fetalis, and neonatal death.Case presentationThis paper details the case of the first Danish patient diagnosed with glucose-6-phosphate isomerase deficiency. The patient, a 27-year-old white female, suffered from lifelong anemia of unknown origin for decades. Diagnosis was established through whole-genome sequencing, which identified two GPI missense variants: the previously documented variant p.(Thr224Met) and a newly discovered variant p.(Tyr341Cys). The pathogenicity of these variants was verified enzymatically.ConclusionsWhole-genome sequencing stands as a potent tool for identifying hereditary anemias, ensuring optimal management strategies.

Meaning-Making Among Parents of Children With Severe Neurologic Impairment in the PICU.

Parents and family caregivers of children with severe neurologic impairment (SNI) experience many stressors, especially during their child's critical illness. This study aimed to examine parent experiences around the time of their child's PICU care to explore ways parents make meaning in relation to these stressors. This qualitative study of data from a single center in the United States followed Consolidated Criteria for Reporting Qualitative Research guidelines. One to one semistructured interviews queried parents' psychosocial well-being around the time of their child's PICU care. Eligible participants had a child with an SNI condition for >3 months admitted to the PICU for >24 hours with an expected length of stay >1 week. Data were analyzed by a research team with expertise in palliative care, psychology, critical care, and qualitative methods. Fifteen family caregivers of 15 children participated. Children were a median of 8 years old (interquartile range 4-11.5) and 80% (n = 12) had congenital/genetic conditions. Parent/family caregivers were a median age of 39 years old (interquartile range 36-42.5); 20% (n = 3) self-identified as fathers and 47% (n = 7) as having to a minority racial background. Parents discussed ongoing meaning-making that occurred through domains of comprehension and purpose, and themes of understanding of other people and the world around them. Subthemes focused on appreciation/acceptance, adaptability/accountability, valuing all lives, and learning/teaching about their child. Meaning-making may be an opportunity for support in the PICU among parents/family caregivers of children with SNI.

Cerebrospinal Fluid Viral Escape on Highly Active Antiretroviral Therapy: Analysis from Single Tertiary Care Centre.

HIV-infected individuals receiving regular antiretroviral therapy (ART) can present with a high viral load in cerebrospinal fluid (CSF) at times when it is suppressed in blood. This study presents data of HIV-infected patients who had undetectable or low plasma viral load in blood but presented with neurological signs and symptoms and were diagnosed to have CSF HIV viral escape. Records were reviewed for clinical manifestations, details of opportunistic or coinfection, and HIV viral copies in plasma and CSF at time of diagnosis of CSF escape. A total of 10,200 HIV-infected individuals were registered in HIV care till December 31, 2021. Nineteen individuals (14 virologically confirmed and 5 clinically) were diagnosed with high viral copies in CSF from June 2014 to December 2021. Mean age was 41.5 ± 9.2 (median, 39.5; range, 30-62) years. Average duration of antiretroviral treatment received at the time of diagnosis of CSF escape was 10.1 years. Median plasma HIV-viral copies were 2,469.8 (undetectable to 29,418) and in CSF were 12,773.7 (n = 14, range, 1,340-48,530) copies/mL. HIV viral copies in CSF were significantly higher than in plasma at the time of presentation (p = .003). ART regimen switch was done after identification of HIV CSF escape. Seventeen patients were alive with a regular follow-up of average 35 (range 7-66) months. All had documented clinical improvement with reversal of neurological impairment after ART switch. There was one death and one lost to follow-up. Early identification and timely intervention in CSF viral escape could revert severe neurological impairment and improves treatment outcome.

A Systematic Review and Meta-Analysis on the Identification of Predictors Associated With Insomnia or Sleep Disturbance in Post-stroke Patients.

The aim of this study was to identify the factors associated with sleep disturbances in individuals after a stroke.To systematically identify relevant studies, an extensive search strategy was devised. We conducted comprehensive searches in major electronic databases including PubMed, Embase, PsycINFO, and Cochrane Library.The search was limited to articles published in English between January 1, 2011, and February 10, 2024.Pooled effect estimates, such as odds ratio (OR) or mean difference (MD) along with their confidence interval (CIs), were calculated using random-effects models for categorical variables and continuous variables, respectively. A total of nine studies were included in this meta-analysis.The pooled prevalence of insomnia across the included studies was determined to be 40% (95% CI = 30%-49%), with individual study prevalence ranging from 22% to 72%. A pooled analysis showed that gender demonstrated a statistically significant association with sleep disturbance, with females exhibiting a higher likelihood (OR = 1.49, 95% CI = 1.16-1.91, p = 0.002) compared to males. The National Institutes of Health Stroke Scale (NIHSS) score, a measure of stroke severity, was associated with sleep disturbance (MD = 0.86, 95% CI = 0.56-1.17, p = 0.001), indicating that patients withsevere strokes may be more prone to sleep disturbances.These findings underscore the importance of comprehensive evaluation and targeted interventions to address sleep-related issues in stroke patients, particularly those with severe neurological impairment.

Video analysis of heading and risk of head injury situations in elite international men's football: Does the frequency of headers increase with the level of play?

AbstractFootball is the only sport in which the ball can be played with the head. Therefore, compared to other ball team sports, head injuries are quite common. Headers and head injuries are dreaded to cause severe neurological impairments in long‐term, but there is still a lack of data on how often headers are performed in different levels and how often head injuries occur. In a prospective cohort study, all heading situations as well as incidents with a propensity of injury (critical incidents) of 45 elite‐level international matches were analyzed using a standardized video analysis protocol and compared to existing data from German professional leagues. A total of 3670 headers were recorded in 4050 match minutes (0.9 headers/minute). A mean of 81.5 headers per game (SD = 18.4) and 3.7 headers per player and match (SD = 0.8) was found. Compared to a cohort group of the German Bundesliga and 2nd Bundesliga, a significant reduction of −33.8 headers per game (p &lt; 0.01) and 1.7 per player and match was found. A total of 18 risk of injury situations were recorded giving a rate per match of 0.4 (SD = 0.6). In comparison to the German league data, this also displayed a reduction. The incidence rate was 266 risk of injury situations per 1000 h match exposure, which was far below the rates of German national data (314/1000 h) and correlated with the frequency of headers performed.

Recurrent Intensive Care Episodes and Mortality Among Children With Severe Neurologic Impairment

Children requiring care in a pediatric intensive care unit (PICU) are known to have increased risk of subsequent mortality. Children with severe neurologic impairment (SNI)-who carry neurologic or genetic diagnoses with functional impairments and medical complexity-are frequently admitted to PICUs. Although recurrent PICU critical illness episodes (PICU-CIEs) are assumed to indicate a poor prognosis, the association between recurrent PICU-CIEs and mortality in this patient population is poorly understood. To assess the association between number of recent PICU-CIEs and survival among children with severe neurologic impairment. This population-based retrospective cohort study used health administrative data from April 1, 2002, to March 31, 2020, on 4774 children born between 2002 and 2019 with an SNI diagnosis code in an Ontario, Canada, hospital record before 16 years of age and a first PICU-CIE from 2002 to 2019. Data were analyzed from November 2021 to June 2023. Pediatric intensive care unit critical illness episodes (excluding brief postoperative PICU admissions). One-year survival conditioned on the number and severity (length of stay >15 days or use of invasive mechanical ventilation) of PICU-CIEs in the preceding year. In Ontario, 4774 children with SNI (mean [SD] age, 2.1 [3.6] months; 2636 [55.2%] <1 year of age; 2613 boys [54.7%]) were discharged alive between 2002 and 2019 after their first PICU-CIE. Ten-year survival after the initial episode was 81% (95% CI, 79%-82%) for children younger than 1 year of age and 84% (95% CI, 82%-86%) for children 1 year of age or older; the age-stratified curves converged by 15 years after the initial episode at 79% survival (95% CI, 78%-81% for children <1 year and 95% CI, 75%-84% for children ≥1 year). Adjusted for age category and demographic factors, the presence of nonneurologic complex chronic conditions (adjusted hazard ratio [AHR], 1.70 [95% CI, 1.43-2.02]) and medical technology assistance (AHR, 2.32 [95% CI, 1.92-2.81]) were associated with increased mortality. Conditional 1-year mortality was less than 20% regardless of number or severity of recent PICU-CIEs. Among children with high-risk PICU-CIEs, 1-year conditional survival decreased from 90% (95% CI, 89%-91%) after the first PICU-CIE to 81% (95% CI, 77%-86%) after the fourth PICU-CIE. This cohort study of children with SNI demonstrated a modest dose-dependent association between PICU-CIEs and short-term mortality. These data did not support the conventional wisdom that recurrent PICU admissions are associated with subsequent high mortality risk.

Acute and Persistent Postoperative Functional Decline in Children with Severe Neurological Impairment: A Qualitative, Exploratory Study.

Children with severe neurologic impairment (SNI) regularly require major surgery to manage their underlying conditions. Anecdotal evidence suggests that children with SNI experience unexpected and persistent postoperative functional changes long after the postoperative recovery period; however, evidence from the perspective of caregivers is limited. The purpose of the study was to explore the functional postoperative recovery process for children with SNI. Eligible participants were English-speaking caregivers of children with SNI between 6 months and 17 years who were nonverbal, Gross Motor Function Classification Scale level IV/V, and who had surgery/procedure requiring general anesthetic at a tertiary children's hospital between 2012 and 2022. Demographic and basic health information were collected via surveys and corroborated by a review of the child's electronic health record. Semi-structured interviews were conducted and a thematic content analysis was used to formulate results. Data from 12 primary caregiver interviews revealed four main themes: (1) functional changes and complications in the child; (2) feeling unprepared; (3) perioperative support; and (4) changes to caregiver roles. Postoperative functional decline in children with SNI was prevalent in our sample. Providing pre-operative information to families to describe this phenomenon should be a regular part of family-informed care.

Timeline of diagnosed pain causes in children with severe neurological impairment.

Pain's causes in children with severe cognitive impairment may be challenging to diagnose. This study aimed to investigate if there is a relationship between pain causes and the age of children. We conducted a multicenter retrospective study in three Italian Pediatric Units. Eligible subjects were patients from 1 to 18 years with severe neurological impairment. We collected data regarding diagnoses, pain causes and medical or surgical procedures. The timing of pain episodes was categorized into age-related periods: infants and toddlers (0-24 months), preschool children (3-5 years), schoolchildren (6-12 years), and adolescents (13-17 years). Eighty children with severe neurological impairment were enrolled. The mean age was 11 years (±5.8). Gastroenterological pain was most common in the first years of life (p = 0.004), while orthopaedic and tooth pain was the most typical in schoolchildren and adolescents (p = 0.001 and p = 0.02). Concerning surgical procedures, PEG placement and gastric fundoplication were significantly more common in the first 5 years of age (p = 0.03), and heart surgery was typical of infants (p = 0.04). Orthopaedic surgery was more commonly reported in older children and adolescents (p < 0.001). Some causes of pain are more frequent in children with severe neurological impairment in defined age-related periods. Specific age-related pain frequencies may help physicians in the diagnostic approach.

Increased risk of complications in lower versus upper limb peripheral intravenous cannulation in children with severe neurological impairment.

Obtaining peripheral intravenous catheter (PIVC) access in children with severe neurological impairment (SNI) is often challenging and commonly associated with complications, including dislodgement, phlebitis and extravasation. In severe cases, extravasation injury may lead to tissue necrosis, ulceration and long-term morbidity. The aim of this study was to determine the relative incidence of PIVC complications secondary to lower limb cannulation, compared to upper limb, in children with SNI. A single centre, retrospective, observational review was conducted. Patients with SNI, admitted at a tertiary paediatric centre over 6months between July and December 2022, were included. One-hundred fifty-five PIVC procedures were conducted in 110 children over the study period. Complications were more common in lower limb PIVCs (12/16, 75%) compared to upper limb (58/139, 42%), p = 0.01. Upper limb cannulation is preferred in children with SNI.

Outcomes of patients with traumatic brain injury after stress ulcer prophylaxis: a retrospective multicenter study

BackgroundStress ulcers in patients with traumatic brain injury (TBI) and spinal cord injury (SCI) present significant morbidity and mortality risks. Despite the low reported stress ulcer rates, stress ulcer prophylaxis...

Safety, Accuracy, and Efficacy of Robot-Assisted Stereo Electroencephalography in Children of Different Ages.

Aimed to investigate the safety, accuracy, and efficacy of stereo electroencephalography (SEEG) in children of various ages, with particular emphasis on those younger than 3 years. There is limited guidance regarding whether SEEG can conducted on very young children. This retrospective study was conducted between July 2018 and August 2022. It involved 88 patients who underwent 99 robot-assisted SEEG procedures at our center. The patients were categorized into 3 groups based on their age at the time of the robot-assisted SEEG procedures: group 1 (3 years and younger, n = 28), group 2 (age 3-6 years, n = 27), and group 3 (older than 6 years, n = 44). Clinical data, SEEG demographics, complications, and seizure outcomes were analyzed. A total of 675 electrodes were implanted, with an average of 6.82 ± 3.47 (2.00-16.00) electrodes per patient (P = .052). The average target point error for the 675 electrodes was 1.93 ± 1.11 mm, and the average entry point error was 1.30 ± 0.97 mm (P = .536 and P = .549, respectively). The overall percentage of complications was 6.06% (P = .879). No severe or long-term neurologic impairment was observed. Of the total 99 procedures included in this study, 78 were admitted for epilepsy surgery for the first time, while 9 patients were treated twice and 1 patient was treated 3 times. There were 21 radiofrequency thermocoagulation and 78 second-stage resective procedures performed after SEEG. There was no statistically significant difference in Engel class I outcomes among the patients who underwent SEEG in the 3 age groups (P = .621). Robot-assisted SEEG were demonstrated to be safe, accurate, and efficient across different age groups of children. This technique is suitable for children younger than 3 years who have indications for SEEG placement.

Long-Term Neurodevelopmental Outcome After Selective Fetoscopic Laser Therapy for Stage I Twin-Twin Transfusion Syndrome.

Twin-twin transfusion syndrome (TTTS) is a serious complication in monochorionic (MC) pregnancies. Fetoscopic laser surgery (FLS) is the primary treatment for advanced TTTS, but managing Quintero stage I TTTS is still controversial. We conducted an observational study evaluating the 2-year neurodevelopment of fetuses, which underwent FLS for stage I TTTS, compared with advanced TTTS and uncomplicated monochorionic diamniotic twins (MCDTs). The study included 156 children: 14 in stage I TTTS group, 28 in advanced TTTS group, and 114 in uncomplicated twin group. In stage I TTTS, 92.9% showed normal neurodevelopment, with no severe neurological impairments observed. These results were comparable with uncomplicated twins (92.1% normal neurodevelopment, P = .921, adjusted odds ratio [aOR] = 1.56, 95% confidence interval [CI] = 0.42-5.79; 1.8% severe impairment, P = .617). Advanced TTTS had a non-significant lower rate of normal neurodevelopment (89.3%, P = .710, aOR = 1.31, 95% CI = 0.12-14.87). In conclusion, FLS for stage I TTTS shows favorable long-term neurodevelopmental outcomes, similar to uncomplicated MC pregnancies.

The evolution of nutrition management in children with severe neurological impairment with a focus on cerebral palsy.

Nutritional management of children with severe neurological impairment (SNI) is highly complex, and the profile of this population is changing. The aim of this narrative review was to give the reader a broad description of evolution of the nutritional management of children with SNI in a high resource setting. In the last decade, there has been an emphasis on using multiple anthropometric measures to monitor nutritional status in children with SNI, and several attempts at standardising the approach have been made. Tools such as the Feeding and Nutrition Screening Tool, the Subjective Global Nutrition Assessment, the Eating and Drinking Ability Classification System and the Focus on Early Eating and Drinking Swallowing (FEEDS) toolkit have become available. There has been an increased understanding of how the gut microbiome influences gastrointestinal symptoms common in children with SNI, and the use of fibre in the management of these has received attention. A new diagnosis, 'gastrointestinal dystonia', has been defined. The increased use and acceptance of blended food tube feeds has been a major development in the nutritional management of children with SNI, with reported benefits in managing gastrointestinal symptoms. New interventions to support eating and drinking skill development in children with SNI show promise. In conclusion, as the life expectancy of people with SNI increases due to advances in medical and nutrition care, our approach necessitates a view to long-term health and quality of life. This involves balancing adequate nutrition to support growth, development and well-being while avoiding overnutrition and its associated detrimental long-term effects.

Early cognitive rehabilitation for patients with severe neurological impairment

Improving the state and future of patients severely impaired following brain injury is at the heart of early rehabilitation, established from the first days of hospitalization. For cognitive deficits, this management involves several challenges, related to hospital conditions and to the patients' capacities during the acute phase. A relevant intervention can be provided, as long as it involves an assessment adapted to these particularities and a rehabilitation targeting the most limiting deficits at this stage. These findings, discussed in the light of our clinical experience and current knowledge in the field, have yet to be scientifically tested since randomized clinical trials are still lacking. The integration of new technologies to facilitate the bedside work presents another prospect for the future.