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Background: Though much research has been done on the cognitive profiles of children, the abilities of patients with SBM as they age into adulthood are not well understood.Objective: Determine if adults with SBM have impairments in overall cognition, attention, executive function, and memory compared to typically developing adults or a standardized population mean.Methods: A medical librarian composed a search of spina bifida, adults, and cognitive function. 549 results were screened using title and abstract. Data were extracted using Covidence review software, including risk of bias assessments. 24 studies were included.Results: Memory impairments, notably working and prospective, have been reported. Results in other domains varied. Average VIQ or PIQ did not imply lack of impairment in other specific domains.Conclusion: Memory impairments should be accounted for and neuropsychological testing should be considered when providing care to adults with SBM. Future longitudinal cognitive aging and interventional studies are needed.

Pneumonia and respiratory infections impact infants and children with Down syndrome; pneumonia is a leading cause of mortality in adults with Down syndrome. We aimed to review the literature to evaluate gaps and address key questions. A series of key questions were formulated a priori to inform the search strategy and review process; addressed prevalence, severity, etiology, risk factors, preventive methods, screening, and financial costs, potential benefits or harms of screening. Using the National Library of Medicine database, PubMed, detailed literature searches on pneumonia and respiratory infections in Down syndrome were performed. Previously identified review articles were also assessed. The quality of available evidence was then evaluated and knowledge gaps were identified. Forty-two relevant original articles were identified which addressed at least one key question. Study details including research design, internal validity, external validity, and relevant results are presented. Pneumonia and respiratory infections are more prevalent and more severe in individuals with Down syndrome compared to healthy controls through literature review, yet there are gaps in the literature regarding the etiology of pneumonia, the infectious organism, risk factors for infection, and to guide options for prevention and screening. There is urgent need for additional research studies in Down syndrome, especially in the time of the current COVID-19 pandemic.

AIM To evaluate presence and severity of social impairments in alternating hemiplegia of childhood (AHC) and determine factors that are associated with social impairments. METHOD This was a retrospective analysis of 34 consecutive patients with AHC (19 females, 15 males; mean age: 9y 7mo, SD 8y 2mo, range 2y 7mo-40y), evaluated with the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS SRS-2 scores, indicating level of social impairment, were higher than population means (75, SD 14 vs 50, SD 10, p 76), four moderate (66-76). All subscale domains, including social cognition, social communication, social awareness, social motivation, restricted interests, and repetitive behavior, had abnormal scores compared to population means (p

Encoding the slow skeletal muscle isoform of myosin binding protein-C, MYBPC1 is associated with autosomal dominant and recessive forms of arthrogryposis. The authors describe a novel association for MYBPC1 in four patients from three independent families with skeletal muscle weakness, myogenic tremors, and hypotonia with gradual clinical improvement. The patients carried one of two de novo heterozygous variants in MYBPC1, with the p.Leu263Arg variant seen in three individuals and the p.Leu259Pro variant in one individual. Both variants are absent from controls, well conserved across vertebrate species, predicted to be damaging, and located in the M-motif. Protein modeling studies suggested that the p.Leu263Arg variant affects the stability of the M-motif, whereas the p.Leu259Pro variant alters its structure. In vitro biochemical and kinetic studies demonstrated that the p.Leu263Arg variant results in decreased binding of the M-motif to myosin, which likely impairs the formation of actomyosin cross-bridges during muscle contraction. Collectively, our data substantiate that damaging variants in MYBPC1 are associated with a new form of an early-onset myopathy with tremor, which is a defining and consistent characteristic in all affected individuals, with no contractures. Recognition of this expanded myopathic phenotype can enable identification of individuals with MYBPC1 variants without arthrogryposis.

PURPOSE: Neurogenic bowel dysfunction (NBD) is a common comorbidity of myelomeningocele (MMC), the most common and severe form of spina bifida. The National Spina Bifida Patient Registry (NSBPR) is a research collaboration between the CDC and Spina Bifida Clinics. Fecal continence (continence) outcomes for common treatment modalities for NBD have not been described in a large sample of individuals with MMC. NSBPR patients with MMC and NBD were studied to determine variation in continence status and their ability to perform their treatment independently according to treatment modality and individual characteristics. METHODS: Continence was defined as < 1 episode of incontinence per month. Eleven common treatments were evaluated. Inclusion criteria were established diagnoses of both MMC and NBD, as well as age ≥ 5 years (n = 3670). Chi-square or exact statistical tests were used for bivariate analyses. Logistic regression models were used to estimate the odds of continence outcomes by age, sex, race/ethnicity, level of motor function, and insurance status. RESULTS: At total of 3670 members of the NSBPR met inclusion criteria between November 2013 and December 2017. Overall prevalence of continence was 45%. Prevalence ranged from 40–69% across different treatments. Among continent individuals, 60% achieved continence without surgery. Antegrade enemas were the most commonly used treatment and had the highest associated continence rate. Ability to carry out a treatment independently increased with age. Multivariable logistic regression showed significantly higher odds of continence among individuals aged ≥ 12 years, female, non-Hispanic white, and with private insurance. CONCLUSIONS: The prevalence of continence was generally low and varied between treatment modalities. Better treatment algorithms considering patient factors may result in improved outcomes.

PURPOSE: Determine the feasibility and utility of using a battery of tests utilized, so far, to assess neurological-cognitive functions in the typical adult population and identify the spectrum of these functions in adult SBM patients. METHODS: Prospective study in which 15 participants (mean age = 28.7 ± 8.7 years, range = 19–45 years) completed the targeted battery of tests (n = 5–15/test) previously standardized to the general population. Results were compared with normative data. RESULTS: Statistically significant differences with normative means were noted in the following tests: Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), and NIH Toolbox Fine Motor (Dexterity and Grip Strength) tests. Cohort means for NIH Toolbox Fluid, Crystallized, and Cognitive Composite Scores and Timed Up and GO (TUG) were not different from normative means. CONCLUSION: All tests were successfully completed by cohort. Whereas many aspects of cognition were normal, tests assessing visual-constructural, calculation, motor, and fluency functions did show differences from population means. Numerous tests assessing multiple domains are needed and can be used in future aging studies to appreciate the spectrum of cognitive and motor abilities in adults with SBM.

Background ATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. Aim We aimed to describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. Methods A retrospective chart review of a cohort of seven patients was conducted. Response to open-label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. Results Patients (age 2.5–20 years) had symptom onset at an early age (6 days–1 year). Seizures were either focal or generalized. Common features were: drug resistance, recurrent status epilepticus, etc., severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks–4.8 years) with some improvements reported in all five. Conclusions Our observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure–function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.

Background Alternating hemiplegia of childhood often manifests severe or extreme behavioral problems, the nature of which remains to be fully characterized. Methods We analyzed 39 consecutive patients with alternating hemiplegia of childhood for occurrence of behavioral problems and categorized those by severity: mild (not requiring intervention), moderate (requiring intervention but no risk), severe (minor risk to self, others, or both), and extreme (major risk). We then analyzed behavioral manifestations, concurrent morbidity, and medication responses in patients with severe or extreme symptoms. Results Two patients had mild behavioral problems, five moderate, 10 severe, six extreme, and 16 none. Extreme cases exhibited disruptive behaviors escalating to assaults. Triggers, when present, included peer-provocation, low frustration tolerance, limits set by others, and sleep disruption. Reversible psychotic symptoms occurred in two patients: in one triggered by infection and trihexyphenidyl, and in another triggered by sertraline. Of the 16 patients with severe or extreme symptoms, 13 had concurrent neuropsychiatric diagnoses. Occurrence of severe or extreme symptoms did not correlate with age, puberty, severity of intellectual disability, or mutation status (P > 0.05). A multidisciplinary team including mental health professionals comanaged all patients with severe or extreme symptoms with either behavioral therapy, medications, or both. When considering medications prescribed to more than four patients, medicines that demonstrated efficacy or partial efficacy in more than 50% of patients were alpha-adrenergic agonists and selective-serotonin-reuptake-inhibitors. Conclusions Patients with alternating hemiplegia of childhood (41%) often experience severe or extreme behavioral problems and, rarely, medication-triggered psychotic symptoms. These observations are consistent with current understanding of underlying alternating hemiplegia of childhood brain pathophysiology. Increasing awareness of these behavioral problems facilitates alternating hemiplegia of childhood management and anticipatory guidance.

To determine the neuropsychological abnormalities that occur in alternating hemiplegia of childhood (AHC) and report on our experience in managing them.Patients underwent evaluations according to our standardized AHC pathway. Data were entered into our prospective AHC database and then analyzed.Of the cohort of 25 consecutive patients (ages 15mo-42y), eight had initial chief complaints about cognition, 14 language, five attention, and 11 behavior. As compared to population norms means, neuropsychological and behavioral assessment tools (including Child Behavior Checklist, Vineland Adaptive Behavior Scales, Peabody Picture Vocabulary, and Wechsler Intelligence Quotient tests) showed significant impairments in multiple domains: cognition, expressive and receptive language, executive function/attention, and behavior (p0.05 in all comparisons). Evaluations generated management recommendations in all patients. Twenty had neuropsychiatric diagnoses: 10 attention-deficit/hyperactivity disorder (ADHD), seven disruptive behavior, and three anxiety disorder. Eight out of nine patients with ADHD who were prescribed medications responded to pharmacotherapy.Patients with AHC have developmental difficulties related to impairments in multiple neuropsychological domains. This supports the hypothesis that the underlying AHC pathophysiology involves diffuse neuronal dysfunction. Testing generated recommendations to help manage these difficulties. Patients with AHC also have a range of neuropsychiatric diagnoses, the most common being ADHD which responds to pharmacotherapy.Patients with alternating hemiplegia of childhood (AHC) have developmental difficulties with underlying neuropsychological impairments. The findings in this study are consistent with an underlying AHC pathophysiology which involves diffuse neuronal, probably largely GABAergic, dysfunction. Patients with AHC have a range of neuropsychiatric diagnoses, the most common being attention-deficit/hyperactivity disorder.PERFILES COGNITIVOS, ADAPTATIVOS Y DE COMPORTAMIENTO Y MANEJO DE LA HEMIPLEJIA ALTERNA EN LA INFANCIA: OBJETIVO: Determinar las anormalidades neuropsicológicas que ocurren en la hemiplejia alterna en la infancia (AHC) y reportar nuestra experiencia en su manejo.Los pacientes fueron evaluados de acuerdo a nuestra evaluación estandarizado de AHC. Los datos fueron introducidos en nuestra base de datos de AHC prospectiva y luego analizados.De la cohorte de 25 pacientes consecutivos (edades 15 meses - 42 años), ocho tenían desafíos iniciales sobre cognición, 14 de lenguaje, cinco de atención y 11 de comportamiento. Comparadas con la población tipica, las herramientas de evaluación neuropsicológica y de comportamiento (incluyendo Child Behavior Checklist, Vineland Adaptive Behavior Scales, Peabody Picture Vocabulary, y Wechsler Intelligence Quotient Tests) mostraron discapacidades significativas en múltiples áreas: cognición, lenguaje expresivo y receptivo, atención y función ejecutiva, y comportamiento (p0.05 en todas las comparaciones). Las evaluaciones generaron recomendaciones de manejo para todos los pacientes. Veinte tenían diagnósticos neuropsiquiátricos: 10 desorden de hiperactividad y déficit de atención (TDAH), siete comportamientos disruptivos, y tres desorden de ansiedad. Ocho de cada nueve pacientes con TDAH a los cuales se les prescribió medicación respondieron a la terapia farmacológica.Los pacientes con AHC tienen dificultades en el desarrollo relacionadas a discapacidades en múltiples áreas neuropsicológicas. Esto apoyo la hipótesis que la fisiopatología AHC subyacente involucra disfunción neuronal difusa. Las evaluaciones generaron recomendaciones para ayudar a manejar esas dificultades. Los pacientes con AHC también tienen un rango de diagnósticos neuropsiquiátricos, siendo TDAH la más común que responde a terapia farmacológica.PERFIL COGNITIVO, ADAPTATIVO E COMPORTAMENTAL DA HEMIPLEGIA ALTERNANTE DA INFÂNCIA: OBJETIVO: Determinar anormalidades neuropsicológicas que ocorrem na hemiplegia alternante da infância (HAI) e relatar nossa experiência com o manejo dos mesmos. MÉTODO: Pacientes passaram por avaliações de acordo com nossa rotina para HAI. Os dados foram entrados em uma base de dados prospectiva e analisados. RESULTADOS: Da coorte de 25 pacientes consecutivos (idades 15m-42a), oito tiveram queixas iniciais importantes sobre cognição, 14 de linguagem, 5 de atenção e 8 de comportamento. Em comparação com valores normativos da população, os instrumentos de avaliação neuropsicológica e comportamental (incluindo Checklist de Comportamento da criança, Escalas Vineland de Comportamento Adaptativo, testes Peabody de Vocabulário pictórico e Quociente de inteligiencia Wechsler) mostraram alterações significativas em múltiplos domínios: cognição, linguagem expressiva e receptiva, função executiva/atenção, e comportamento (p0,05 em todas as comparações). As avaliações geraram recomendações de manejo em todos os pacientes. Vinte tiveram diagnósticos neuropsiquiátricos: 10 com transtorno de déficit de atenção e hiperatividade (TDAH), sete comportamento disruptivo, e três transtorno de ansiedade. Oito dos nove pacientes com TDAH que foram prescritos medicação responderam a farmacoterapia. INTERPRETAÇÃO: Pacientes com HAI têm dificuldades neurodesenvolvimentais relacionadas a deficiências em múltiplos domínios neuropsicológicos. Isso suporta a hipótese de que a fisiopatologia básica da HAI envolve disfunção neuronal difusa. As avaliações geraram recomendações que ajudaram a manejar estas dificuldades. Pacientes com HAI também têm uma variedade de diagnósticos neuropsiquiátricos, o mais comum sendo TDAH que responde a farmacoterapia.

Background Youth with special health care needs often experience difficulty transitioning from pediatric to adult care. These difficulties may derive in part from lack of physician training in transition care and the challenges health care providers experience establishing interdisciplinary partnerships to support these patients. Objective This educational innovation sought to improve pediatrics and adult medicine residents' interdisciplinary communication and collaboration. Methods Residents from pediatrics, medicine-pediatrics, and internal medicine training programs participated in a transitions clinic for patients with chronic health conditions aged 16 to 26 years. Residents attended 1 to 4 half-day clinic sessions during 1-month ambulatory rotations. Pediatrics/adult medicine resident dyads collaboratively performed psychosocial and medical transition consultations that addressed health care navigation, self-care, and education and vocation topics. Two to 3 attending physicians supervised each clinic session (4 hours) while concurrently seeing patients. Residents completed a preclinic survey about baseline attitudes and experiences, and a postclinic survey about their transitions clinic experiences, changes in attitudes, and transition care preparedness. Results A total of 46 residents (100% of those eligible) participated in the clinic and completed the preclinic survey, and 25 (54%) completed the postclinic survey. A majority of respondents to the postclinic survey reported positive experiences. Residents in both pediatrics and internal medicine programs reported improved preparedness for providing transition care to patients with chronic health conditions and communicating effectively with colleagues in other disciplines. Conclusions A dyadic model of collaborative transition care training was positively received and yielded improvements in immediate self-assessed transition care preparedness.

Aim To characterize motor function profiles in alternating hemiplegia of childhood, and to investigate interrelationships between these domains and with age. Method We studied a cohort of 23 patients (9 males, 14 females; mean age 9y 4mo, range 4mo–43y) who underwent standardized tests to assess gross motor, upper extremity motor control, motor speech, and dysphagia functions. Results Gross Motor Function Classification System (GMFCS), Gross Motor Function Measure-88 (GMFM-88), Manual Ability Classification System (MACS), and Revised Melbourne Assessment (MA2) scales manifested predominantly mild impairments; motor speech, moderate to severe; Modified Dysphagia Outcome and Severity Scale (M-DOSS), mild-to moderate deficits. GMFCS correlated with GMFM-88 scores (Pearson's correlation, p=0.002), MACS (p=0.038), and MA2 fluency (p=0.005) and accuracy (p=0.038) scores. GMFCS did not correlate with motor speech (p=0.399), MA2 dexterity (p=0.247), range of motion (p=0.063), or M-DOSS (p=0.856). Motor speech was more severely impaired than the GMFCS (p