Down syndrome (DS) is one of the most well-recognized genetic disorders. Persons with DS are known to have a variety of co-morbid medical problems, affecting nearly all organ systems. Improved ...healthcare interventions and research have allowed for increased life span of persons with DS, although disorders of the neurologic system remain underexplored. The purpose of this systematic review is to provide clinically pertinent information on the neurological phenotypes of frequently occurring or clinically relevant conditions. A retrospective review of MEDLINE, Scopus, and Pubmed were used to identify sources among seventeen, clinically relevant, search categories. MeSH terms all contained the phrase “Down Syndrome” in conjunction with the topic of interest. ‘Frequently-occurring’ was defined as prevalent in more than 10% of persons with DS across their lifespan, whereas ‘clinically-relevant’ was defined as a disease condition where early diagnosis or intervention can augment the disease course. In total, 4896 sources were identified with 159 sources meeting criteria for inclusion. Seventeen clinical conditions were grouped under the following subjects: hypotonia, intellectual and learning disability, cervical instability, autism spectrum disorder, epilepsy, cerebrovascular disease, Alzheimer’s disease and neuropsychiatric disease. The results of this review provide a blueprint for the clinical neurologist taking care of persons with DS across the age spectrum and indicate that there are many underrecognized and misdiagnosed co-occurring conditions in DS, highlighting the need for further research.
Objective
To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome.
Background
There are no consensus criteria ...for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area.
Methods
The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome.
Results
During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on “other” studies) as were diagnostic criteria (96% agreement).
Conclusions
The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.
Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with ...Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention.
A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms.
Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64-37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88-9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective.
This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology.
Immunizations against Hepatitis B virus (HBV) and Varicella Zoster virus (VZV), are recommended for patients with pediatric onset multiple sclerosis (POMS) and may be required prior to initiation of ...some disease modifying therapies. However, the efficacy of routine vaccine administration in POMS has never been studied. We sought to assess the humoral mediated vaccine response to HBV and VZV in children with POMS.
A multi-center retrospective chart-based review of 62 patients with POMS was performed. Clinical data and antibody titers against HBV and VZV were collected prior to initiation of disease modifying therapy or steroids and compared to institutional control data, using
-test and chi squared analysis.
There were low rates of immunity against both HBV and VZV (33 and 25% respectively) among individuals with POMS. Fifteen individuals (24%) were non-immune to both. Compared to institutional control data, individuals with POMS were significantly less likely to be immune to and HBV (
= 0.003, 95% CI: 0.22-0.75) and VZV (
< 0.001, 95% CI: 0.09-0.39).
Individuals with POMS have low rates of antibody-mediated immunity against HBV and VZV, despite receiving the appropriate vaccinations. This suggests an association between POMS and systemic immune dysregulation although further study is needed.
Regulatory and ethical considerations mandate that minorities affected by health disparities be included in research. Despite concerns about clinical outcomes for patients with obesity, clinical ...trials have reported few data about participation of and outcomes for such patients. This article examines the lack of body size diversity in clinical research participants and reviews the evidence and ethical arguments for including larger-bodied patients. Drawing on examples of improved gender diversification of trial participants, this article suggests that similar benefits would be likely from inclusion of body diversity.
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.
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.
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.
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.
•Nearly all disease modifying therapies used in children with demyelinating disorders carries a category C, D, or x FDA-pregnancy categorization.•In young females of childbearing potential with ...demyelinating disorders, utilization of contraception was found to only 1/3rd of those with similar chronic conditions and the general population.•Utilization of contraception in individuals of hispanic descent was markedly lower than other ethnic and racial groups.•Further study into the ethnic and racial disparities, safety, and need for contraception in females of childbearing potential with demyelinating disorders is needed.
Demyelinating disorders in young females are frequently treated with immunomodulatory therapy which often have unknown risks to fetuses during pregnancy. In spite of this, there is no literature in this population about the use of contraception. Our objective was to determine the rate of use of contraception used in a real-world cohort of pediatric patients on immunotherapy for demyelinating diseases.
A retrospective, multi-center, chart-based review was performed. Inclusion criteria was female gender, use of immunotherapy for a demyelinating disorder, and age >11 years.
Fifty-six female patients were identified with an average age of 15.4 years. The most common demyelinating disorders was multiple sclerosis (n = 33, 59%). The most common treatments were rituximab (n = 18, 32%), dimethyl fumarate (n = 13, 23%), IVIg (n = 11, 20%), and fingolimod (n = 11, 20%). Overall, only 16% (n = 9) of patients used contraception at any point during their immunotherapy regimen. Hispanic patients accounted for 41% of the cohort but were uniformly not on contraceptives (p = 0. 02). Contraceptive use did not impact ARR in any disease (p = 0.45).
Contraceptive use in young females with demyelinating disorders is less than 1/3rd of the general population with particular discrepancies in persons of Hispanic/Latino descent.
Display omitted
PDF
