Association of Gestational Age at Birth and Changes on MRI With Prevalence and Spectrum of Comorbidities in Children With Cerebral Palsy.

BACKGROUND AND OBJECTIVES: For individuals with cerebral palsy (CP) and caregivers, comorbidities may be a greater challenge than neuromotor impairment. Clinicians may make assumptions regarding risk of comorbidities based simply on term vs preterm birth, but this has not been well examined. To better understand factors affecting comorbidity pattern, we investigated the relationship between gestational age (GA) and imaging pattern on the presence of specific comorbidities. METHODS: This is a cross-sectional study of data extracted from the Canadian Cerebral Palsy Registry of children with CP. Multivariable analysis was used to evaluate the relationship between brain injury, GA, and comorbidities. Comorbidities included in the analysis were communication, cognitive, visual, and auditory impairment, seizures in the past year, and gavage feeding. Each comorbidity was assessed as a separate nonexclusive outcome, with GA, MRI pattern, birth weight, postneonatal insult, 5-minute Apgar score, and male sex considered as potential modifiers. RESULTS: The only comorbidity affected by GA on multivariable analysis was seizures within the past year that were more prevalent in term children (odds ratio [OR] 1.1 95% CI 1.0-1.2) and was also affected by Apgar score (OR 0.9 95% CI 0.85-0.94), but not MRI pattern. MRI pattern appeared important for communication impairment (deep gray OR 4.2 95% CI 1.8-10.0; total brain injury OR 8.5, 95% CI 3.2-22.6; malformation OR 2.7, 95% CI 1.3-5.7) and cognitive impairment (deep gray OR 5.6, 95% CI 2.4-13.2; total brain injury OR 10.1, 95% CI 4.0-25.3; malformation OR 3.3, 95% CI 1.6-6.8; watershed OR 3.6, 95% CI 1.4-8.9). Focal injury compared with normal MRI was associated with reduced odds of visual impairment (OR 0.24, 95% CI 0.12-0.48), auditory impairment (OR 0.2195% CI 0.10-0.46) and communication impairment (OR 0.46, 95% CI 0.26-0.82), and overall number of comorbidities (coefficient -0.73, 95% CI -1.2 to -0.31). The number of comorbidities was increased by total brain injury pattern (coefficient 0.65, 95% CI 0.15-1.13) and reduced by focal brain injury (coefficient -0.73, 95% CI -1.2 to -0.31) and increasing 5-minute Apgar score (coefficient -0.11, 95% CI -0.16 to -0.07). DISCUSSION: In those with brain injuries sufficient to cause CP, development of additional comorbidities is less affected by GA at birth and more related to the underlying cause of CP as reflected by MRI patterns.

Characteristics of Children With Cerebral Palsy in the Post-Therapeutic Hypothermia Era.

Objectives: To explore the profile of children with cerebral palsy secondary to intrapartum asphyxia treated with therapeutic hypothermia after birth and to compare characteristics of children treated with therapeutic hypothermia with mild vs severe cerebral palsy outcome. Study Design: We identified all children treated with therapeutic hypothermia for intrapartum asphyxia in a single-center tertiary-level neonatal intensive care unit from 2008 to 2018 with a cerebral palsy outcome. We collected perinatal and outcome measures from patient charts. We searched the literature for characteristics of children with cerebral palsy prior to therapeutic hypothermia (historical cohort) to compare to our cohort. We subdivided our cohort into mild vs severe cerebral palsy and compared neonatal characteristics to identify predictors of severe phenotype. Results: Thirty of 355 cooled neonates (8%) developed cerebral palsy. More children had spastic quadriparesis and epilepsy, and fewer had visual impairment in the post-therapeutic hypothermia era compared to the historical cohort, but had similar Gross Motor Function Classification System scores. In our cohort, more children had severe (19 of 30, 63%) compared to mild cerebral palsy (11 of 30, 37%). The severe group had higher mean birth weight, lower 5- and 10-minute Apgar scores, and more often white matter injury with associated deep gray matter injury or near-total injury pattern (P < .05). Conclusions: Our data demonstrated more infants with severe rather than mild cerebral palsy in our cohort treated with therapeutic hypothermia. Birthweight, 5- and 10-minute Apgar scores, and magnetic resonance imaging (MRI) findings were significantly different between mild and severe phenotype groups. Our findings can guide clinicians how to better weigh these factors, when counseling parents in the neonatal period.

Development and validation of a salivary tau biomarker in Alzheimer's disease.

INTRODUCTION: Total tau (t-tau) and phosphorylated tau (p-tau) are abnormally elevated in the brain and cerebrospinal fluid of individuals with Alzheimer's disease (AD). Tau is also present in the salivary gland tissue and saliva, and salivary measures might produce an accurate, accessible, and inexpensive biomarker. METHODS: Using unstimulated saliva and Western blot analysis, we quantified the p-tau/t-tau ratio at different phosphorylation sites. RESULTS: We found that for one phosphorylation site, S396, p-tau/t-tau ratio was significantly elevated in patients with AD compared with normal elderly control subjects. The elevation in saliva, however, did not correlate with cerebrospinal fluid tau or with brain measures such as hippocampal volume. DISCUSSION: There is significant elevation of p-tau/t-tau ratio for the S396 phosphorylation site. Large variation in the AD salivary tau levels, however, limits the utility of this test as a clinical biomarker.

Diagnostic Yield of Intellectual Disability Gene Panels.

BACKGROUND: Recent technological advances have improved the understanding and identification of the genetic basis of intellectual disability (ID) and global developmental delay (GDD). Next-generation sequencing panels of ID genes are now available for clinical testing; however, their overall yield in clinical practice has not yet been investigated. AIM: We determined the diagnostic yield of ID gene panels in a clinical setting and explored whether any clinical features are associated with an increased diagnostic yield. METHODS: We performed a systematic retrospective chart review of all patients with ID/GDD who underwent an ID gene panel between April 2014 and July 2017 at our institution. Chi-square analysis assessed whether any specific clinical features were significantly associated with a positive diagnostic yield. RESULTS: Forty-eight subjects (18 females, 30 males; median age: 7.5 years) were included. Consanguinity was present in 17%, autism in 38%, seizures in 42%, nonspecific dysmorphic features in 67%, and abnormalities on neurological examination in 56%; furthermore, 29% of the cohort was nonverbal and 4% was nonambulatory. Four different gene panels were used. The diagnostic yield was 21% (10/48) overall, and 38% with the more recent trio-based panel. Eight of 10 patients had de novo pathogenic dominant mutations, one had an inherited pathogenic autosomal dominant mutation, and one had compound heterozygous pathogenic recessive mutations. No clinical feature was significantly associated with an increased diagnostic yield. CONCLUSIONS: Our study suggests that ID gene panels have a high yield and are a valuable diagnostic tool in the evaluation of children with ID/GDD.