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ABSTRACT: As newer, innovative neurology drugs enter the US health care system, neurologists should consider the cost of these treatments in addition to their efficacy, safety, and tolerability. To do so thoughtfully requires an understanding of how prescription drugs are priced in the United States. The process of drug pricing is linked to the distribution supply chain and the many stakeholders involved. Stakeholders include pharmaceutical manufacturers; wholesalers; pharmacies; pharmacy benefit managers; payers, including health insurers; hospital systems; neurologists and other clinicians; and patients. Drug pricing has taken center stage as the Inflation Reduction Act of 2022 has set maximum out-of-pocket expenses for Medicare beneficiaries for the first time in the program's history and limits drug price increases for a select group of Medicare Part D drugs. This article describes the US drug distribution supply chain and its stakeholders and introduces key drug pricing terms; a brief description of how rebates are generally estimated will also be discussed. Finally, as newer neurology outpatient drugs enter the market, the "value" of drugs will be described through cost-effectiveness terminology and their utility for the clinical neurologist.
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Costos de los Medicamentos , Neurólogos , Humanos , Estados Unidos , Neurólogos/economía , Medicamentos bajo Prescripción/economíaRESUMEN
BACKGROUND: Isolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE. METHODS: This multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed. RESULTS: Of 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy. CONCLUSIONS: Isolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.
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Background: Autoimmune encephalitis (AIE) comprises a group of rare, immune system-mediated conditions. Clinical manifestations among children are not well-characterized, and there are challenges in testing and diagnosis. This can result in treatment delays, which has been found to correlate with poorer long-term outcomes. This challenge is exacerbated by the scarcity of epidemiological reporting of AIE. The objective of this systematic literature review (SLR) was to identify studies reporting epidemiological data on AIE in children. Methods: MEDLINE, Embase, the Cochrane Library, and the University of York Centre for Reviews and Dissemination (CRD) were searched in May 2023 for studies reporting on the epidemiology of AIE in children. These were supplemented with additional searches of conference proceedings, gray literature, and the reference lists of identified SLRs. Quality of studies was assessed using a modified version of the Joanna Briggs Institute (JBI) Checklist for Prevalence Studies. Results: Forty-three publications reporting on 41 unique studies were included. Nine studies reported incidence estimates of different subtypes of AIE, with only one reporting the incidence of overall AIE in children ≤ 18 years, estimated at 1.54 per million children per year in the Netherlands. Three studies reported the incidence of pediatric N-methyl-D-aspartate receptor (NMDAR)-AIE [in United Kingdom (UK), Hong Kong, and Denmark]. The other studies reported incidence data for selected populations. Conclusion: This SLR highlights a paucity of epidemiology data for AIE in children, which is likely reflective of difficulties in testing and diagnosis. There is a clear need for further research and awareness of these challenges in clinical practice to avoid treatment delays and improve patient outcomes. A deeper understanding of the epidemiology of AIE will help determine the worldwide burden of disease and inform research, health policies and clinical decision-making.
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BACKGROUND: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD. METHODS: This study included individuals with DSRD aged 10-30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher's exact test) were used to describe and compare the characteristics of individuals with and without variants. RESULTS: Forty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic (UNC13D, XIAP, RNASEH2A, and DNASE1L3). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger (p = 0.03, 95% CI 1.21-97.06), rapid clinical decline in less than 1 month (p = 0.01, 95% CI 1.67-52.06), and MRI abnormalities (p < 0.001, 95% CI 4.89-527.71). DISCUSSION: A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS.
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Síndrome de Down , Humanos , Síndrome de Down/genética , Síndrome de Down/inmunología , Masculino , Niño , Femenino , Adolescente , Adulto , Adulto Joven , Secuenciación del ExomaRESUMEN
BACKGROUND: Disease-modifying therapies (DMTs) have revolutionized the management of multiple sclerosis (MS). Many DMTs have a risk of teratogenic outcomes, which is notable as MS disproportionally affects women of reproductive age and the rates of unplanned pregnancies among persons with MS (PwMS) are as high as 34%. Prior research suggests that patients' culture may influence their perspectives surrounding family planning. Given our institution's patient population, we compared the spectrum of knowledge in Hispanic and non-Hispanic patients with pediatric-onset MS (POMS) regarding DMTs and their associated risks during pregnancy and possible disparities in their treatment and counseling. METHODS: A small cohort of patients with POMS (n = 22) were surveyed on their knowledge and beliefs surrounding family planning and sexual health counseling. Odds ratios and 95% confidence intervals were used to evaluate the association between survey question responses and ethnicity. RESULTS: No significant differences in beliefs or knowledge regarding sexual health between Hispanic and non-Hispanic participants were identified, but many valuable themes emerged. Internet access and social relationships heavily influence participants' knowledge surrounding birth control and sexual health. Patients also desired continuous engagement in sexual health counseling. CONCLUSIONS: In this small pilot cohort, cultural views did not significantly influence whether adolescent and young adult patients with POMS seek sexual health resources. Future studies should aim to identify effective interventions for providers to educate PwMS about sexual health and family planning to address the elevated unplanned pregnancy rate in this population and provide the education these patients have vocalized a desire to receive.
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Consejo , Conocimientos, Actitudes y Práctica en Salud , Hispánicos o Latinos , Esclerosis Múltiple , Salud Sexual , Humanos , Femenino , Esclerosis Múltiple/terapia , Esclerosis Múltiple/etnología , Adolescente , Conocimientos, Actitudes y Práctica en Salud/etnología , Masculino , Adulto Joven , Consejo/normas , Adulto , Embarazo , Estudios de Cohortes , Educación Sexual , Proyectos Piloto , Servicios de Planificación FamiliarRESUMEN
Down syndrome is the most common genetic cause of intellectual disability and has previously been associated with a variety of autoimmune disorders affecting multiple organ systems. The high prevalence of autoimmune disease, in conjunction with other inflammatory and infectious diseases, in this population suggests an intrinsic immune dysregulation associated with triplication of chromosome 21. Emerging data on the role of chromosome 21 in interferon activation, cytokine production, and activation of B-cell mediated autoimmunity are emerging hypotheses that may explain the elevated prevalence of autoimmune thyroid disease, celiac disease, type I diabetes, autoimmune skin disease, and a variety of autoimmune neurologic conditions. As the life expectancy for individuals with Down syndrome increases, knowledge of the epidemiology, clinical features, management and underlying causes of these conditions will become increasingly important. Disorders such as Hashimoto's thyroiditis are prevalent in between 13 and 34% of individuals with Down syndrome but only 3% of the neurotypical population, a pattern similarly recognized in individuals with Celiac Disease (5.8% v 0.5-2%), alopecia areata (27.7% v. 2%), and vitiligo (4.4% v. 0.05-1.55%), respectively. Given the chronicity of autoimmune conditions, early identification and management can significantly impact the quality of life of individuals with Down syndrome. This comprehensive review will highlight common clinical autoimmune conditions observed in individuals with Down syndrome and explore our current understanding of the mechanisms of disease in this population.
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OBJECTIVE: To evaluate association between time to initiation of disease modifying treatment (DMT) and outcomes in pediatric-onset Multiple Sclerosis (POMS). METHODS: A retrospective analysis of children with POMS from two tertiary referral pediatric Neuroimmunology clinics. Outcome measures comprised annualized relapse rate (ARR), MRI lesion burden (T1, T2-FLAIR, and post-GAD contrast sequences), EDSS, and 25-ft walk duration at the latest follow-up visit. Univariate and multivariate analysis using linear and logistic regression models were used to assess associations between patient characteristics and outcomes. RESULTS: In total, 68 patients were reviewed. More than half of patients were female (62 %) and 32 (47 %) were Hispanic/LatinX. Median age at diagnosis was 14.2 years (IQR: 11.0-16.5), and median duration from diagnosis to the latest follow-up was 2.5 years (IQR: 1.6-4.6). Sensory (29.4 %), brainstem (23.5 %), and pyramidal (19.1 %) symptoms were most common. Interferon beta (32.4 %), dimethyl fumarate (27.9 %) and rituximab (26.5 %) were the most frequently used first-line DMT. Patients had a median ARR of 0.5 (IQR: 0.08-0.84), and EDSS score of 1.0 (IQR: 0.0-2.0) at the most recent follow-up. Delayed DMT initiation correlated with higher ARR (R = 0.38, p = 0.0016) and longer 25-ft walk duration (R = 0.34, p = 0.0077). In multivariate analysis, delayed DMT remained a significant predictor of higher ARR (p = 0.002) and longer 25-ft walk duration (p = 0.047). Delayed DMT initiation and use of low/moderate efficacy DMT predicted GAD enhancing lesions at the latest follow-up (p = 0.004 and 0.019 respectively). CONCLUSION: Delayed DMT initiation in POMS is linked to unfavorable outcomes, including higher ARR and longer 25-ft walk duration.
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Recurrencia , Humanos , Femenino , Masculino , Niño , Adolescente , Estudios Retrospectivos , Factores Inmunológicos/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/fisiopatología , Imagen por Resonancia Magnética , Tiempo de Tratamiento , Estudios de SeguimientoRESUMEN
Metachromatic leukodystrophy (MLD) is a fatal, progressive neurodegenerative disorder caused by biallelic pathogenic mutations in the ARSA (Arylsulfatase A) gene. With the advent of presymptomatic diagnosis and the availability of therapies with a narrow window for intervention, it is critical to define a standardized approach to diagnosis, presymptomatic monitoring, and clinical care. To meet the needs of the MLD community, a panel of MLD experts was established to develop disease-specific guidelines based on healthcare resources in the United States. This group developed a consensus opinion for best-practice recommendations, as follows: (i) Diagnosis should include both genetic and biochemical testing; (ii) Early diagnosis and treatment for MLD is associated with improved clinical outcomes; (iii) The panel supported the development of newborn screening to accelerate the time to diagnosis and treatment; (iv) Clinical management of MLD should include specialists familiar with the disease who are able to follow patients longitudinally; (v) In early onset MLD, including late infantile and early juvenile subtypes, ex vivo gene therapy should be considered for presymptomatic patients where available; (vi) In late-onset MLD, including late juvenile and adult subtypes, hematopoietic cell transplant (HCT) should be considered for patients with no or minimal disease involvement. This document summarizes current guidance on the presymptomatic monitoring of children affected by MLD as well as the clinical management of symptomatic patients. Future data-driven evidence and evolution of these recommendations will be important to stratify clinical treatment options and improve clinical care.
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Leucodistrofia Metacromática , Humanos , Recién Nacido , Cerebrósido Sulfatasa/genética , Consenso , Terapia Genética/métodos , Leucodistrofia Metacromática/terapia , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/genética , Tamizaje Neonatal/métodos , Estados UnidosRESUMEN
BACKGROUND: Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. OBJECTIVE: To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. METHODS: We analyzed children (≤ 18 y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). RESULTS: We included 103 children with RIS (67% girls, median age = 14.9 y). Children ≥ 12 y were more likely than children < 12 y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12 y (median 11d vs. 159d, p = 0.03). CONCLUSIONS: Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.
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Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Niño , Adolescente , Estudios Longitudinales , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Factores de Edad , Factores Sexuales , Enfermedades Desmielinizantes/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/diagnósticoRESUMEN
OBJECTIVE: To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses. METHODS: A multicenter, retrospective, case-control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10-30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities. RESULTS: In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p < 0.001, 95%CI: 2.18-7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) (p = 0.18, OR: 1.63, 95%CI: 0.79-3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) (p < 0.001, OR: 7.31, 95%CI: 2.83-18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p < 0.001, OR: 8.42. 95%CI: 3.78-18.76) and less likely to respond to benzodiazepines (p = 0.01, OR: 0.45, 95%CI: 0.25-0.83), antipsychotics (p < 0.001, OR: 0.28, 95%CI: 0.11-0.55), or electroconvulsive therapy (p < 0.001, OR: 0.12; 95%CI: 0.02-0.78) compared to individuals without these neuroimaging abnormalities. INTERPRETATION: This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy.
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Síndrome de Down , Humanos , Síndrome de Down/terapia , Estudios Retrospectivos , Estudios de Casos y Controles , Neuroimagen/métodos , InmunoterapiaRESUMEN
Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy characterized by upregulation of type I interferon response. It is associated with increased mortality and severe disabilities. Janus Kinase (JAK) inhibitors have shown effectiveness in treatment of AGS through blocking the downstream effects of interferon activation. We illustrate post-mortem histopathologic findings in a patient with AGS who received baricitinib treatment for a duration of over 4 years, initiating at a remarkably young age of 2 months. We observed global cerebral atrophy, markedly diminished white matter, abundant calcifications involving supratentorial white matter, basal ganglia, dentate nuclei, and brainstem. This study showed profound central nervous system (CNS) sequelae despite early initiation of treatment. Our findings highlight the potential necessity for therapeutic options with enhanced CNS bioavailability.
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Enfermedades Autoinmunes del Sistema Nervioso , Inhibidores de las Cinasas Janus , Malformaciones del Sistema Nervioso , Humanos , Lactante , Inhibidores de las Cinasas Janus/uso terapéutico , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Enfermedades Autoinmunes del Sistema Nervioso/genética , Progresión de la EnfermedadRESUMEN
This position statement serves to establish the AAN's stance on the methods to address the cost of prescription drugs being considered by state and federal policymakers so that the AAN can continue to advocate effectively for its members. Neurologists seek to provide high-value care for patients with neurologic diseases at the lowest cost possible. However, many therapies for neurologic diseases are among the most expensive in the United States. The 3 major cost challenges include (1) unjustified increases in the pricing for drugs used to treat neurologic disorders, (2) the high cost of medications used to treat rare diseases where there are limited or no therapeutic options available, and (3) the high cost of noninnovative (already FDA-approved) therapies that used accelerated FDA approval pathways or Orphan Drug Act designated to expedite approvals in neurologic disorders. In each of these cases, AAN is concerned that the high cost does not deliver sufficient value to patients or society. The AAN's position is that action must be taken to ensure that effective prescription medications are accessible for patients with complex, chronic neurologic conditions. Potential solutions should be affordable, simple, and transparent. Cost-containment efforts must also address the burden on the entire healthcare system because high prescription drug prices may be shifted and absorbed in ways that negatively affect patient and prescriber access to important medications. AAN supports price negotiations, the cost saving potential of generics and biosimilars, development of novel therapeutics, price transparency, and importation.
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Biosimilares Farmacéuticos , Enfermedades del Sistema Nervioso , Medicamentos bajo Prescripción , Humanos , Estados Unidos , Producción de Medicamentos sin Interés Comercial , PrescripcionesRESUMEN
Three large multi-center studies have identified the clinical utility of intravenous immunoglobulin (IVIg) in the treatment of Down syndrome regression disorder (DSRD). Yet the tolerability of infusions in individuals with DS and the safety of IVIg remains unknown in this population. This study sought to evaluate the safety and tolerability of IVIg in individuals with DSRD compared to a real-world cohort of individuals with pediatric onset neuroimmunologic disorders. A single-center, retrospective chart review evaluating clinically documented infusion reactions was performed for individuals meeting international consensus criteria for DSRD and having IVIg infusions between 2019 and 2023. Infusion reactions were evaluated for severity and need for alterations in infusion plan. This cohort was compared against an age and sex matched cohort of children with neuroimmunologic conditions who had also received IVIg infusions. In total, 127 individuals with DSRD and 186 individuals with other neuroimmunologic disorders were enrolled. There was no difference in the overall rate of adverse reactions (AEs) between the DSRD and general neuroimmunology cohorts (p = 0.31, 95% CI: 0.80-2.00), but cardiac-related AEs specifically were more common among the DSRD group (p = 0.02, 95% CI: 1.23-17.54). When AEs did occur, there was no difference in frequency of pharmacologic intervention (p = 0.12, 95% CI: 0.34-1.13) or discontinuation of therapy (p = 0.74, 95% CI: 0.06-7.44). There was a higher incidence of lab abnormalities on IVIG among the general neuroimmunology cohort (p = 0.03, 95% CI: 0.24-0.94) compared to the DSRD cohort. Transaminitis was the most common laboratory abnormality in the DSRD group. In a large cohort of individuals with DSRD, there were no significant differences in the safety and tolerability of IVIg compared to a cohort of children and young adults with neuroimmunologic conditions.
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Síndrome de Down , Inmunoglobulinas Intravenosas , Niño , Adulto Joven , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Estudios Retrospectivos , Síndrome de Down/complicaciones , Síndrome de Down/tratamiento farmacológicoAsunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Enfermedad de Moyamoya , Malformaciones del Sistema Nervioso , Enfermedades Vasculares , Humanos , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Enfermedad de Moyamoya/complicaciones , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/terapia , InmunoterapiaRESUMEN
BACKGROUND: Around 40% of individuals with epilepsy have an underlying identifiable genetic etiology. Common methods for epilepsy genetic testing are chromosomal microarray (CMA) and epilepsy-genes sequencing (EGS). Historically, CMA was the first-line test for patients with epilepsy, but recent studies have shown that EGS has a superior diagnostic yield. To further optimize testing algorithms for epilepsy, we compared these tests' diagnostic yields and explored how they are influenced by age of onset and phenotype complexity. METHODS: Genetic test results from a cohort of patients with epilepsy were used to determine the diagnostic yield of CMA (n = 366) versus EGS (n = 370) for genetic epilepsy etiologies. Further analysis examined the probability of diagnostic results based on age of seizure onset and patients' phenotype complexity. RESULTS: For patients who underwent CMA, causative variants were found in 28 of 366 cases (7.7%), and 60 of 366 patients (16.4%) had at least one variant of uncertain significance (VUS). For EGS, 65 of 370 (17.6%) cases had causative variants, whereas 155 of 370 (41.9%) had at least one VUS. EGS had a significantly higher diagnostic yield than CMA (odds ratio [OR] = 2.63, P < 0.001). This difference in diagnostic yield was further pronounced among patients with infantile seizure onset (OR = 4.69, P < 0.001) and patients with additional neurological findings (OR = 2.99, P < 0.001). CONCLUSION: To minimize the time and resources required to reach a diagnosis, clinicians and insurers alike should consider using EGS as an initial diagnostic tool.
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Epilepsia , Niño , Humanos , Epilepsia/diagnóstico , Epilepsia/genética , Pruebas Genéticas/métodos , Análisis por Micromatrices , Fenotipo , Convulsiones/genéticaRESUMEN
Background: Pediatric onset multiple sclerosis (POMS) commonly occurs at the time of various endocrine changes. Evaluation of the impact of endocrine status on disease severity in POMS has not been previously explored. Objective: This study sought to evaluate if sex and stress hormones in children with POMS impact motor and non-motor diseases severity. Methods: A single-center case control study was performed. Individuals with POMS were compared to individuals without neurologic disease. Each individual had three blood draws assessing stress and sex hormones between 07:00 and 09:00. Measures of fatigue (Epworth sleepiness scale), depression (PHQ-9), and quality of life (PedsQL) assessed at each visit. Results: Forty individuals with POMS and 40 controls were enrolled. Individuals with POMS had lower free testosterone (p = 0.003), cortisol (p < 0.001), and ACTH (p < 0.001) and had higher progesterone (p = 0.025) levels than controls. Relapses and EDSS were not impacted by endocrine variables. The POMS cohort had a significantly higher Epworth score (p < 0.001), PHQ-9 score (p < 0.001), and lower PQL score (p < 0.001) than controls. Non-motor measures were not associated with endocrine status. Conclusion: Free testosterone, cortisol, ACTH, and progesterone were abnormal in children with POMS although there was no association between endocrine status and markers of disease severity or non-motor symptoms of MS.
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BACKGROUND: Plasma levels of vitamin D have been reported to be low in persons with Down syndrome (DS) and existing data is limited to small and homogenous cohorts. This is of particular importance in persons with DS given the high rates of autoimmune disease in this population and the known relationship between vitamin D and immune function. This study sought to investigate vitamin D status in a multi-center cohort of individuals with DS and compare them to individuals with autism spectrum disorder (ASD) and neurotypical (NT) controls. METHODS: A retrospective, multi-center review was performed. The three sites were located at latitudes of 42.361145, 37.44466, and 34.05349. Patients were identified by the International Classification of Diseases (ICD)-9 or ICD-10 codes for DS, ASD, or well-child check visits for NT individuals. The first vitamin D 25-OH level recorded in the electronic medical record (EMR) was used in this study as it was felt to be the most reflective of a natural and non-supplemented state. Vitamin D 25-OH levels below 30 ng/mL were considered deficient. RESULTS: In total, 1624 individuals with DS, 5208 with ASD, and 30,775 NT controls were identified. Individuals with DS had the lowest mean level of vitamin D 25-OH at 20.67 ng/mL, compared to those with ASD (23.48 ng/mL) and NT controls (29.20 ng/mL) (p < 0.001, 95% CI: -8.97 to -6.44). A total of 399 (24.6%) individuals with DS were considered vitamin D deficient compared to 1472 (28.3%) with ASD and 12,397 (40.3%) NT controls (p < 0.001, 95% CI: -5.43 to -2.36). Individuals with DS with higher body mass index (BMI) were found to be more likely to have lower levels of vitamin D (p < 0.001, 95% CI: -0.3849 to -0.1509). Additionally, having both DS and a neurologic diagnosis increased the likelihood of having lower vitamin D levels (p < 0.001, 95% CI: -5.02 to -1.28). Individuals with DS and autoimmune disease were much more likely to have lower vitamin D levels (p < 0.001, 95% CI: -6.22 to -1.55). Similarly, a history of autoimmunity in a first-degree relative also increased the likelihood of having lower levels of vitamin D in persons with DS (p = 0.01, 95% CI: -2.45 to -0.63). CONCLUSIONS: Individuals with DS were noted to have hypovitaminosis D in comparison to individuals with ASD and NT controls. Associations between vitamin D deficiency and high BMI, personal autoimmunity, and familial autoimmunity were present in individuals with DS.
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Trastorno del Espectro Autista , Enfermedades Autoinmunes , Síndrome de Down , Deficiencia de Vitamina D , Humanos , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/diagnóstico , Síndrome de Down/complicaciones , Estudios Retrospectivos , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Enfermedades Autoinmunes/complicacionesRESUMEN
BACKGROUND: Acute flaccid myelitis (AFM) presents with acute onset of flaccid paralysis with involvement of the gray matter on magnetic resonance imaging (MRI) of the spinal cord. Studies have reported brain MRI abnormalities, but the characteristics have not been fully defined. In this multicenter study, we assessed the acute features and evolution of brain MRI abnormalities in AFM. METHODS: We reviewed brain MRIs of patients with AFM who presented to four referral hospitals between 2012 and 2018. Cases met established criteria for AFM. We analyzed the initial and follow-up brain MRIs. Areas were divided into supratentorial, infratentorial, and subdivisions within those regions. RESULTS: A total of 66 patients were included. Brain MRI abnormalities were present in 34 (52%). Infratentorial abnormalities were more common, occurring in 33 (97%) cases with the dorsal pons being the most frequently affected area (88%). Abnormalities were also present in the medulla (74%), cerebellum (41%), and midbrain (38%). Nine subjects (26%) exhibited both supratentorial and infratentorial abnormalities, whereas isolated supratentorial changes were present in only one (3%). Contrast-enhancing abnormalities were encountered in 9% of cases and meningeal involvement in 6%. On follow-up, most abnormalities, 20 of 24 (83%), were stable, improving, or had resolved. CONCLUSIONS: Brain MRI abnormalities occur in about half of the cases of AFM and commonly resolve with time. Dorsal pontine involvement is a characteristic MRI feature, whereas isolated supratentorial abnormalities are rare. Clinicians should consider that brain imaging abnormalities do not exclude a diagnosis of AFM in patients with typical presentations.
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Encefalopatías , Malformaciones del Sistema Nervioso , Enfermedades Neuromusculares , Humanos , Imagen por Resonancia Magnética , Enfermedades Neuromusculares/diagnóstico por imagen , Cerebelo , Estudios Multicéntricos como AsuntoRESUMEN
Down syndrome, also known as Trisomy 21, is a genetic disorder associated with mild-to-moderate intellectual disability, delays in growth, and characteristic facial features. A wide range of ocular complications are seen in children with Down syndrome, including strabismus, nystagmus, refractive errors, congenital cataracts, the presence of keratoconus, and decreased visual acuity. Early ophthalmic examination is needed for early diagnosis and treatment in patients. This narrative review examines ocular manifestations in children with Down syndrome and the importance of prompt ophthalmic interventions for treatment.