Severe Neurological Impairment Research Articles

4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model

Abstract Sandhoff disease (SD), a fatal and rare lysosomal storage disorder (LSD), is caused by a deficiency of the enzyme β-hexosaminidase B and leads to severe accumulation of GM2 gangliosides in lysosomes, primarily within the central nervous system (CNS). This accumulation results in severe neurological impairment, lower motor neuron disease, and death. Currently, there are no effective therapies available for SD. Here, we explored the role of endoplasmic reticulum (ER) stress in the spinal cord during disease progression in an established mouse model of SD and revealed the beneficial outcome of off-label treatment with the FDA-approved drug, 4-phenylbutyric acid (4-PBA). We analyzed the expression and localization of ER stress and cellular apoptosis markers, which revealed significant upregulation of these factors within motor neurons. Additionally, we observed a > 50% reduction in neuronal numbers throughout all spinal cord regions. Our studies also tested the impact of the chemical chaperone 4-PBA on ER stress in mice, and following administration, we observed significant improvements in motor neuromuscular function and life span throughout disease progression. 4-PBA treatment significantly reduced apoptosis in spinal cord neurons and increased the number of choline acetyltransferase (ChAT)-positive neurons, with little effect on astrogliosis or sensory interneurons. Overall, this study provides strong evidence for the role of chronic ER stress in the pathophysiology of SD and highlights 4-PBA as a promising therapeutic treatment for SD and potentially other related LSDs.

Candidacy Decisions for Long-term Ventilation.

Decisions to initiate long-term ventilation (LTV) in children with severe neurologic impairment have recently been subject to candidacy determinations by home ventilation teams that exclude patients based on their neurologic status alone. Determinations of whether decisions are inappropriate require careful analysis of specific clinical circumstances and attention to the family's values. In this Ethics Rounds, we present a case of a previously healthy child who sustained an acute severe anoxic brain injury and was assessed by the medical team to have a high likelihood of remaining minimally conscious or unconscious. It was determined that he was not a candidate for LTV based on the severity of neurologic impairment. The family disagreed and declined withdrawal of ventilatory support. Drawing upon our backgrounds in intensive care, pulmonology, and bioethics, we offer commentary on utilizing a candidacy-based approach for LTV decisions in children with severe neurologic impairment from variable perspectives, including clinical determinations of inappropriate care, ablest biases and discrimination, and obligations to maintain a just process.

Repercussion of Primary Nucleation Pathway: Dementia and Cognitive Impairment.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and prion disease, are characterized by the conversion of normally soluble proteins or peptides into aggregated amyloidal fibrils. These diseases result in the permanent loss of specific types of neurons, making them incurable and devastating. Research on animal models of memory problems mentioned in this article contributes to our knowledge of brain health and functionality. Neurodegenerative disorders, which often lead to cognitive impairment and dementia, are becoming more prevalent as global life expectancy increases. These diseases cause severe neurological impairment and neuronal death, making them highly debilitating. Exploring and understanding these complex diseases offer significant insights into the fundamental processes essential for maintaining brain health. Exploring the intricate mechanisms underlying neurodegenerative diseases not only holds promise for potential treatments but also enhances our understanding of fundamental brain health and functionality. By unraveling the complexities of these disorders, researchers can pave the way for advancements in diagnosis, treatment, and ultimately, improving the lives of individuals affected by neurodegenerative diseases.

Towards a treatment for thyroid hormone transporter MCT8 deficiency: achievements and challenges.

Patients with an inactive thyroid hormone (TH) transporter MCT8 (Allan-Herndon-Dudley Syndrome, AHDS) display severe neurological impairments and motor disabilities indicating an indispensable function of MCT8 in facilitating TH access to the human brain. As a consequence, the CNS of AHDS patients appears to be in a TH deficient state which greatly compromises proper neural development and function. As another hallmark of this disease, patients exhibit elevated serum T3 levels leading to a hyperthyroid situation in peripheral tissues. Several treatment strategies have been developed and evaluated in preclinical mouse models as well as in patients. Here, we discuss these different therapeutic approaches to overcome MCT8 deficiency and summarize the current achievements and challenges in improving brain maturation in the absence of MCT8.

A Five-year Study of Spinal Disorders among Patients Presenting to the National Trauma Center of Nepal: An Observational Study

Introduction: Spinal cord injuries result in severe neurological impairments and disabilities. With an estimated 15.4 million cases globally in 2021, spinal cord injuries are more common in low- and middle-income countries, yet research in these areas is limited. This study aimed to find the pattern of spinal injuries and outcomes associated with spine injuries over a five-year duration at a tertiary trauma care center. Methods: This observational cross-section study was conducted at the National Trauma Center, Kathmandu from 2075 to 2080 B.S. with ethical clearance from the Nepal Health Research Council (Reference number: 968). Total-population sampling was used. A structured proforma was employed as the primary data collection tool. Data was analyzed using SPSS. Results: Of the 20843 patients, 2070 (9.93%) had spinal injuries. The median age was 43 (IQR 32-56) years, with 1391 (67.20%) male patients. The median hospital stay was 12 (IQR 7-20) days. Falls accounted for 1221 (58.99%) cases, and road traffic accidents for 195 (9.42%). Spinal fractures were present in 1076 (51.98%) patients with 456 (42.38%) in lumbar vertebra. There were 225 (10.87%) cases of subluxation with 214 (95.11%) in cervical level. Conclusions: The study provides insights into the patterns and outcomes of spinal injuries over five years of time. The mortality rate and cases of patients leaving against medical advice highlight areas for improvement in patient care and follow-up.

Variability in treatment of postoperative pain in children with severe neurologic impairment.

Treatment of postoperative pain for children with severe neurologic impairment (SNI) is challenging. We describe the type, number of classes, and duration of postoperative pain medications for procedures common among children with SNI, as well as the variability across children's hospitals in pain management with an emphasis on opioid prescribing. This retrospective cohort study included children with SNI ages 0-21 years old who underwent common procedures between January 1, 2019 and December 31, 2019 within 49 children's hospitals in the Pediatric Health Information System. We defined SNI using previously described high-intensity neurologic impairment diagnosis codes and identified six common procedures which included fracture treatment, tracheostomy, spinal fusion, ventriculoperitoneal shunt placement (VP shunt), colostomy, or heart valve repair. Medication classes included benzodiazepines, opioids, and other nonopioid pain medications. Acetaminophen and nonsteroidal anti-inflammatory drugs were excluded from analysis. All findings were summarized using bivariate statistics. A total of 7184 children with SNI underwent a procedure of interest. The median number of classes of pain medications administered varied by procedure (e.g., VP shunt: 0 (interquartile range [IQR] 0-1); tracheostomy: 3 (IQR 2-4)). Across all procedures, opioids and benzodiazepines were the most commonly prescribed pain medications (48.8% and 38.7%, respectively). We observed significant variability in the percentage of postoperative days with opioids across hospitals by procedure (all p < .001). There is substantial variability in the postoperative delivery of pain medications for children with SNI. A standardized approach may decrease the variability in postoperative pain control and enhance care for children with SNI.

Modern Russian drugs for the treatment of neurodegenerative diseases

Neurodegenerative diseases are characterized by progressive death of nerve cells of certain types with concomitant atrophy of the corresponding parts of the spinal cord or brain, which is symptomatically manifested by severe neurological and cognitive impairment. These diseases can manifest at any age and be caused by both genetic predisposition and inflammatory and autoimmune processes. Diseases of this group are a common cause of disability and mortality. Thus, the development of new effective domestic drugs for their treatment is an important task for the healthcare system of the Russian Federation. In this review is devoted to the analysis of Russian original and bioanalog organic and genetically engineered drugs for the treatment of neurodegenerative diseases that have been registered in recent years or are currently undergoing clinical trials in Russia.

Determination of Health Concepts in β-Propeller Protein-Associated Neurodegeneration.

β-Propeller protein-associated neurodegeneration (BPAN) is a rare, X-linked condition caused by pathogenic variants in the WDR45 gene that result in a defect of autophagy. Classified as a disorder of neurodegeneration with brain iron accumulation, β-propeller protein-associated neurodegeneration is associated with severe neurologic impairments. With the anticipation of future therapeutic trials, this project characterizes the family's perspective of the impact of disease and defines Health Concepts (HC).Children with a molecularly confirmed diagnosis of β-propeller protein-associated neurodegeneration were enrolled in a prospective natural history study. We administered the Vineland Adaptive Behavior Scales-Third Edition and provided health-related quality of life questionnaires to 42 caregivers. Questionnaires included Pediatric Quality of Life Inventory-Generic Core and Pediatric Quality of Life Inventory-Family Impact modules, Caregiver Priorities and Child Health Index of Life with Disabilities, and Caregiver TBI-CareQoL.The Vineland Adaptive Behavior Scales-Third Edition (n = 42) captured the family's perspective that communication was more affected compared with socialization, activities of daily living (ADL), and motor skills (P < .0001, P < .0001, P = .0053, respectively). Similarly, on the Caregiver Priorities and Child Health Index of Life with Disabilities (n = 26), Pediatric Quality of Life Inventory-Generic Core (n = 27), CareQol (n = 26), and Pediatric Quality of Life Inventory-Family Impact (n = 27), communication abilities, as well as social functioning and activities of daily living, were noted to be most impacted.Through the use of standardized surveys and outcome assessments, we establish the effects of β-propeller protein-associated neurodegeneration on caregiver quality of life. Key health concepts identified by families included overall health, comfort, and communication. The identified HC will inform the future identification of concept of interest and selection of appropriate clinical outcome assessments through the administration of patient-reported outcomes.

Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances

BackgroundNeurodegenerative diseases (NDDs) are a diverse group of neurological disorders with progressive neuronal loss at specific brain regions, leading to impaired cognitive functioning, loss of neuroplasticity, severe neurological impairment, and dementia. The incidence of neurodegenerative diseases is increasing at an alarming rate with current treatments struggling to barely prolong the inevitable. The desperation to discover a therapeutic agent to treat neurodegenerative diseases and to aid in the process of healthy recovery has opened a gateway into natural pigments. HypothesisThe xanthophyll pigment lutein may bear the potential as a therapeutic agent against NDDs. ResultsLutein plays an important role in brain development, cognitive functioning, and improving neuroplasticity. In vitro and in vivo studies revealed the neuroprotective properties of lutein against NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. The neuroprotective effect of lutein is evidenced by the reduction of free radicals and the simultaneous strengthening of the endogenous antioxidant systems by activating the NRF-2/ERK/AKT pathway. Further, it effectively suppressed mitochondrial aberrations, excitotoxicity, overaccumulation of metals, and its resultant complications. The immunomodulatory activity of lutein prevents neuroinflammation by hindering NF-κB nuclear translocation, regulation of NIK/IKK, PI3K/AKT, MAPK/ERK, JNK pathways, and ICAM-1 downregulation. Lutein also rescued the dysregulated cholinergic system and resolved memory defects. Along with its neuroprotective properties, lutein also improved neuroplasticity by enabling neurogenesis through increased GAP-43, NCAM, and BDNF levels. ConclusionLutein exhibits strong neuroprotective activities against various NDDs. Though the investigations are in the exploratory phase, this review presents the consolidation of scattered evidence of the neuroprotective properties of lutein and urges its further exploration in clinical studies.

Assessment of the quality of life of cats affected by paraparesis/paraplegia and urinary retention, and their impact on caregivers.

In cats affected by severe thoracolumbar spinal cord pathologies, paraplegia and paraparesis, often accompanied by urinary retention, pose significant challenges, impacting both the cats' welfare and owners' lives. This study aimed to assess the quality of life (QoL) of cats affected by these conditions, and to evaluate the social and familial implications for caregivers. The study was structured into two parts. The first part comprised direct observations of aspects of QoL in cats both in household and shelter settings, while the second part involved the distribution of questionnaires to cat owners and shelter operators. Cats with paraplegia/paraparesis and urinary retention can maintain a good QoL, with hindlimb mobility significantly influencing QoL scores. Shelter cats showed a comparable QoL to household cats, challenging the anecdotal beliefs that shelter cats with severe neurological impairments are destined to lead substandard lives. Operator surveys highlighted the feasibility of managing these cats in shelter environments, emphasising the importance of collaboration between caregivers and veterinary professionals. Likewise, owner surveys revealed a manageable time commitment for care, with most owners achieving proficiency in manual bladder expression within 1 month. Despite challenges, most of the owners reported positive experiences and did not contemplate euthanasia for their cats. Regular veterinary visits and occasional physiotherapy were common practices among caregivers. Owners who respond to the questionnaire and shelter operators have a high commitment to cats with paraplegia/paraparesis. Although the study acknowledges this potential bias, it suggests that dedicated care can ensure a good QoL for cats with severe spinal injuries, both in shelter and household settings. Effective communication between caregivers and veterinary professionals is essential for accurate information dissemination and optimal care provision. This research contributes to raising awareness of managing these conditions and emphasises the importance of collaborative care approaches in veterinary medicine.

S4680 Severe Neurological Impairments Due to Marchiafava-Bignami Disease in the Setting of Chronic and Continued Alcohol Abuse and Malnutrition

S4680 Severe Neurological Impairments Due to Marchiafava-Bignami Disease in the Setting of Chronic and Continued Alcohol Abuse and Malnutrition

Clinical management of a ruptured intracranial aneurysm

BackgroundIntracranial hemorrhage due to a ruptured aneurysm is one of the most serious neurosurgical emergencies. The patient mostly presents with severe headaches and neurological deterioration. A rapid diagnosis and an interdisciplinary approach play a major role in the fate of these patients. The treatment can vary from endovascular to surgical and must be carefully and individually planned. Neurovascular expertise and an interdisciplinary approach are of vital importance and obligatory for the best possible outcome.MethodsIn this narrative review, we scrutinize the current literature and discuss the actual data and guidelines in order to emphasize the importance of the interdisciplinary expertise and approach in patients with ruptured intracranial aneurysm.ResultsThe current approach to patients with ruptured aneurysm is inhomogeneous and often ineffective due to internal disputes between different disciplines. Although there is plenty of literature and hard evidence to “show the way,” many still choose to base their decisions on personal experience or opinion.ConclusionsEvery ruptured brain aneurysm should be approached in an interdisciplinary manor and treated according to the current evidence and guidelines.

Characteristics and outcomes of home parenteral nutrition among children with severe neurological impairment.

To describe the characteristics, secular trends, and outcomes of home parenteral nutrition (HPN) use among children with severe neurological impairment (SNI) and non-primary digestive disorders from 2010 to 2023 and compare outcomes to children with primary digestive disorders on HPN. A retrospective review of all children with SNI and non-primary digestive disorders, where HPN was initiated between January 2010 and September 2023 at a tertiary care pediatric hospital. The Mann-Kendall trend test was used to assess trends in HPN initiation. We compared acute care service utilization in the year prior and following HPN initiation. Mortality and ability to achieve enteral autonomy outcomes were compared to those of children with HPN and primary digestive disorders. Of the 205 included children with HPN, 18 children had SNI and non-primary digestive disorders, 187 children had primary digestive disorders. There was an increase in HPN initiation among children with SNI and non-primary digestive disorders (p = 0.002) between 2010 and 2020. Among children with SNI and non-primary digestive disorders, HPN-related complications (line-associated infection/thrombus, nephrolithiasis, cholelithiasis) occurred in 72%. There was no change in acute care utilization in the year prior versus year following HPN initiation. Compared with the primary digestive disorders group, children with SNI and non-primary digestive disorders were less likely to achieve enteral autonomy (p < 0.0001); however, no significant differences in mortality were observed (22% vs. 8%, p = 0.09). HPN is increasingly being used among SNI children with non-primary digestive disorders. Compared to children with primary digestive disorders on HPN, those with SNI are less likely to achieve enteral autonomy.

Electrolyte Imbalance in Acute Traumatic Brain Injury: Insights from the First 24 h.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride, and calcium levels. This study aims to provide insights into these disturbances within the first 24 h post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. The results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

Controlled automated reperfusion of the whole body after cardiac arrest: Device profile of the CARL system.

Cardiac arrest is associated with high mortality rates and severe neurological impairments. One of the underlying mechanisms is global ischemia-reperfusion injury of the body, particularly the brain. Strategies to mitigate this may thus improve favorable neurological outcomes. The use of extracorporeal cardiopulmonary membrane oxygenation (ECMO) during CA has been shown to improve survival, but available systems are vastly unable to deliver goal-oriented resuscitation to control patient's individual physical and chemical needs during reperfusion. Recently, controlled automated reperfusion of the whoLe body (CARL), a pulsatile ECMO with arterial blood-gas analysis, has been introduced to deliver goal-directed reperfusion therapy during the post-arrest phase. This review focuses on the device profile and use of CARL. Specifically, we reviewed the published literature to summarize data regarding its technical features and potential benefits in ECPR. Peri-arrest, mitigating severe IRI with ECMO, might be the next step toward augmenting survival rates and neurological recovery. To this end, CARL is a promising extracorporeal oxygenation device that improves the early reperfusion phase after resuscitation.

Burden of Congenital CMV Infection: A Narrative Review and Implications for Public Health Interventions.

Cytomegalovirus causes the most common congenital infection worldwide. With most infants asymptomatic at birth, the few affected may present with variable clinical scenarios, from isolated hearing loss to severe neurologic impairment. Public health interventions include all actions at the health system, community, and individual levels that aim at reducing the burden of congenital Cytomegalovirus. This review examines the literature on maternal and neonatal screening programs in light of current evidence for treatment and the development of vaccines against Cytomegalovirus. Potential biases and benefits of these interventions are outlined, with the objective of increasing awareness about the problem and providing readers with data and critical tools to participate in this ongoing debate.

Psychosocial experiences of clinicians providing care for children with severe neurological impairment.

Psychosocial experiences of clinicians providing care for children with severe neurological impairment.

Osteoporotic vertebral fracture: Our Experience and update

Introduction: Osteoporotic vertebral fracture is a fragility fracture due to osteoporosis and is a growing public health problem. It mainly affects postmenopausal women and men &gt; 50 years. It significantly affects morbidity, financial condition, quality of life and mortality of patients. It presents mainly with back pain, which is mostly manageable with conservative measures. Those with unrelieved pain, severe spinal deformity or neurological impairment would require intervention. The quality of bone and surgical fitness along with associated co-morbidities of these elderly people, require special consideration, indications and appropriate modification of technique and instruments for surgical intervention. Materials and methodology: This prospective study summarizes the management of osteoporotic vertebral fractures from September 2015 to September 2021 in Nepal Medical College, Kathmandu, Nepal. The study included patients with back pain of more than 50 years old age. The backpain was evaluated clinically using visual analogue scale and Oswestry Disability Index, neurological deficits using Frankel grading system and deformity using X-ray. Other investigations included MRI, Dexa scan, Serum calcium and Vitamin D3. Risk factors for developing osteoporosis and OVF were also assessed. Results: Out of the 630 patients of more than 50 years age, presenting in neurosurgical OPD with backache from September 2015 to September 2020, 158 cases were later diagnosed to have osteoporotic spine fractures. There were 122 (77.2%) postmenopausal ladies and 36 (22.8%) gentlemen. All had backpain, with 36% having VAS score of &lt; 3 and 64% had ODI of mild to moderate disability. The neurological deficits were present in 16.4% and mostly were Frankel grade C and D. Significant kyphoscoliosis (Cobb angle more than 20 degrees) in X-ray was present in 18 (11.3%) patients. 88 (55.7%) patients had Dexa scan and T score was less than -2.5 in 88 (56%). Serum calcium was low in (41) 26% and Vitamin D3 was low in (107) 67.7% of the patients. For backpain, all were started on non-operative management. Vertebral augmentation procedure was not available in our institute. Thus, surgery was offered in 44 (28%) of the patients but only 18 (11.4%) agreed for surgery and underwent decompression with long segment fixation. Only 48 patients remained in follow up for more than 2 years and all had satisfactory control of pain with no deterioration in deformity or neurological deficit. There were no significant short or long-term complications or mortality. Conclusion: Osteoporotic vertebral fracture is a very common reason for back pain in people of more than 50 years old affecting their livelihood. The majority responded to conservative treatment. Those indicated for surgery need special consideration in preparation, technique and devices. Preventive measures can help reduce the problem load.

“I'm completely off base here on what this child is capable of”: A qualitative analysis of how medical ableism manifests in PICU clinicians' care of children with severe neurological impairment

BackgroundChildren with severe neurological impairment (SNI) are at heightened risk of experiencing medical ableism from clinicians in the pediatric intensive care unit (PICU), where barriers such as time scarcity and heavy workloads limit clinicians’ ability to provide personalized care. ObjectiveTo examine medical ableism and strategies to support PICU clinicians in understanding the lives of children with SNI and their families. MethodsThis US-based, single-center, qualitative study included PICU clinicians identified by the parents/caregivers of a child with SNI. Semi-structured 1:1 60-min interviews about the challenges of caring for children with SNI were conducted virtually. Coded data were extracted, thematically analyzed, and further conceptualized using the Dual Process Theory (DPT) bias reduction framework. ResultsNineteen PICU clinicians participated. Three major themes emerged: 1) assumptions and misconceptions about children with SNI and their families, 2) barriers to providing personalized care, and 3) clinician-suggested strategies to honor the lives of children with SNI. These themes aligned with the DPT framework. As outlined in the DPT, system 1 “fast thinking” errors occur when quick observations inform decisions (e.g., snap judgments about a child's capabilities). Second, barriers (e.g., insufficient time for meaningful interactions) may prevent clinicians from providing unbiased care. Third, system 2 “slow thinking,” where complex decision-making occurs, and can be enhanced through personalization strategies (e.g., viewing visuals of the child at baseline health). ConclusionsIncreasing clinician awareness of their potential implicit biases and utilizing bias reduction strategies to mitigate medical ableism in care are critical areas for future research.

Nonverbal Cognitive Skills in Children With Aicardi Goutières Syndrome.

Aicardi Goutières syndrome (AGS) is type I interferonopathy characterized by severe neurologic impairment. Although many children with AGS demonstrate motor and expressive language deficits, the magnitude of receptive language impairment is uncharacterized. We sought to characterize cognitive function in AGS-affected children using assessment tools with reduced dependence on motor abilities and compare cognitive testing outcomes with overall severity and parental assessment of adaptive behavior. We performed a cross-sectional study. Children were recruited as part of the Myelin Disorders Biorepository Project at the Children's Hospital of Philadelphia. We included individuals with a confirmed diagnosis of AGS. We administered the Leiter International Performance Scale, third edition (Leiter-3), and the Vineland Adaptive Behavior Scale, third edition (VABS-3), in the context of research encounters. Motor skills were categorized by AGS Severity Scale mobility levels. Descriptive statistics and Spearman's rank correlation were used to compare assessments. Mann-Whitney and Kruskal-Wallis tests with correction with Dunn's multiple comparison test were used to compare test performance between mobility groups. Cognitive and adaptive behavior performance was captured in 57 children. The mean age at encounters was 8.51 (SD 5.15) years. The median (IQR) Leiter-3 score was 51 (interquartile range [IQR] 60), with administration failure in 20 of 57 (35%) individuals. On the VABS-3, the Motor Domain (median 29, IQR 36.25) was more impacted than the Communication (median 50, IQR 52), Daily Living Skills (median 52, IQR 31), and Socialization (median 54, IQR 40) Domains (p < 0.0001). The AGS Scale correlated with VABS-3 (r = 0.86, p < 0.0001) and Leiter-3 (r = 0.87, p < 0.0001). There was correlation between VABS-3 Domains and Leiter-3 (r-range 0.83-0.97). Gross motor and fine motor categories, respectively, correlated with VABS-3 (H = 39.37, p < 0.0001; U = 63, p < 0.0001) and Leiter-3 (H = 40.43, p < 0.0001; U = 66, p < 0.0001). Within each gross motor and fine motor category of the AGS Scale, a subset of children scored within normal IQ range. Parental assessment of function by the VABS-3 correlated with directly assessed performance measures. Our data underscore the potential value of VABS-3 and Leiter-3 as tools to assess psychometric function in AGS. With a deeper understanding of our patients' abilities, we can better guide clinicians and families to provide appropriate support and personalized interventions to empower children with leukodystrophies to maximize their communication and educational potential.