Adults with tuberous sclerosis complex: A distinct patient population.

OBJECTIVES: There are few data on adults living with tuberous sclerosis complex (TSC), with most studies focusing on pediatric populations. The objective of our study was to examine a large national cohort of adults with TSC, and to describe the clinical characteristics of these adults and the nature of the multidisciplinary care that they receive. METHODS: Six Canadian medical centers collaborated in this study. Data were collected using a standardized form, and descriptive statistics were used for the analyses. RESULTS: Our study included 181 adults with definite TSC (mean age = 33.6 years [SD = 13.7]). More than 40% (n = 75) had family members affected by TSC. Forty-six percent (n = 83) of individuals had intellectual disability. Nearly 30% (n = 52) of individuals reported living alone or with a partner/spouse. Seventy-six percent (n = 138) of people had epilepsy, 43% (n = 59) of whom had drug-resistant epilepsy, and 21% (n = 29) had undergone epilepsy surgery. Neuropsychiatric disease (n = 128) and renal angiomyolipomas (n = 130) were both present in approximately 70% of people. Renal imaging was performed in 75.7% (n = 137) of participants within the past 3 years. Renal and pulmonary function tests, as well as electrocardiograms, were recently performed in a minority of individuals. SIGNIFICANCE: Our cohort of adults with TSC showed that an important proportion have a milder phenotype, and are more frequently familial, as compared to children with TSC (and differing from prior reports in adult cohorts). Drug-resistant epilepsy, neuropsychiatric comorbidities, and renal angiomyolipoma are challenging factors in adults with TSC. Our participating medical centers generally followed recommended screening strategies, but there remain important gaps in care. Multidisciplinary and structured TSC care centers offering service to adults may help to improve the health of this important patient population.

Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans.

Neural tube defects (NTDs) are a heterogeneous group of common severe congenital anomalies which affect 1-2 infants per 1000 births. Most genetic and/or environmental factors that contribute to the pathogenesis of human NTDs are unknown. Recently, however, pathogenic mutations of VANGL1 and VANGL2 genes have been associated with some cases of human NTDs. Vangl genes encode proteins of the planar cell polarity (PCP) pathway that regulates cell behavior during early stages of neural tube formation. Homozygous disruption of PCP genes in mice results in a spectrum of NTDs, including defects that affect the entire neural axis (craniorachischisis), cranial NTDs (exencephaly) and spina bifida. In this paper, we report the dynamic expression of another PCP gene, Fuzzy, during neural tube formation in mice. We also identify non-synonymous Fuzzy amino acid substitutions in some patients with NTDs and demonstrate that several of these Fuzzy mutations affect formation of primary cilia and ciliary length or affect directional cell movement. Since Fuzzy knockout mice exhibit both NTDs and defective primary cilia and Fuzzy is expressed in the emerging neural tube, we propose that mutations in Fuzzy may account for a subset of NTDs in humans.

Sex and gender differences in epilepsy.

Sex and gender differences in epilepsy are important influencing factors in epilepsy care. In epilepsy, the hormonal differences between the sexes are important as they impact specific treatment considerations for patients at various life stages particularly during early adulthood with establishment of the menstrual cycle, pregnancy, perimenopause and menopause. Choice of antiseizure medication may have direct consequences on hormonal cycles, hormonal contraception, pregnancy and fetal risk of major congenital malformation. Conversely hormones whether intrinsic or extrinsically administered may have direct impact on antiseizure medications and seizure control. This chapter explores these important influences on the management of persons with epilepsy.

Resident Use of EEG Cap System to Rule Out Nonconvulsive Status Epilepticus.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) requires an EEG for diagnosis and in many centers access may be limited. The authors aimed to test whether neurology residents can be trained to use and interpret full-montage EEGs using an EEG cap electrode system to detect NCSE while on-call. METHODS: Neurology residents were trained to interpret EEG recordings using the American Clinical Neurophysiology Society critical care EEG terminology. Residents who achieved a score of 70% or higher in the American Clinical Neurophysiology Society certification test and attended a training session were eligible to use the EEG cap on-call with patients suspected of having NCSE. Residents' experience and interpretation of observed EEG patterns were evaluated using a questionnaire. Each EEG recording was independently reviewed by three epilepsy specialists to determine the interpretability of each study and whether the residents correctly identified the EEG patterns. RESULTS: Sixteen residents undertook the training and 12 (75%) achieved a score of 70% or higher on the certification test. Seven of these residents performed 14 EEG cap studies between August 2017 and May 2018. The percent agreement between residents and electroencephalographers was 78.6% for EEG interpretability and 57.1% for description of EEG pattern. Residents did not miss any malignant patterns concerning for NCSE, which accounted for 1 of 14 EEGs but "overcalled" patterns as malignant in 3 of 14 recordings. CONCLUSIONS: This study suggests that neurology residents can be taught to perform and interpret EEGs using a cap system to monitor for NCSE. Additional training will help improve EEG interpretation and sensitivity.

Term neonatal encephalopathy antecedent cerebral palsy: a retrospective population-based study.

OBJECTIVE: To compare the clinical profile of term-born cerebral palsy children with or without antecedent moderate to severe neonatal encephalopathy. We hypothesized that antecedent neonatal encephalopathy is associated with a spastic quadriparesis cerebral palsy clinical profile, a higher severity of functional motor impairment, and a greater number of associated comorbidities. METHODS: Using the Quebec Cerebral Palsy Registry, neurologic subtype, Gross Motor Function Classification System stratification, and comorbidities were compared in children with cerebral palsy with and without antecedent neonatal encephalopathy. Differences between groups were evaluated using chi square analysis for categorical variables and student t test for continuous variables. RESULTS: We identified 132 children with cerebral palsy born full term over a 4 year-interval (1999-2002 inclusive) within the Quebec Cerebral Palsy Registry, of which 44 (33%) had an antecedent neonatal encephalopathy. Spastic quadriplegia subtype of cerebral palsy and Gross Motor Function Classification System Level III-V (non-independent ambulation) were significantly associated with antecedent neonatal encephalopathy. The mean number of comorbidities experienced was not different in the two groups. Of five documented comorbidities, only severe communication difficulties were found to be associated (p < 0.05) with antecedent neonatal encephalopathy. CONCLUSION: A pattern of increased neuromotor impairment, functional gross motor severity and possible communication difficulties was found in the 33% of children with cerebral palsy born at term and with a history of neonatal encephalopathy.

Does antenatal tobacco or alcohol exposure influence a child's cerebral palsy? A population-based study.

Antenatal tobacco and alcohol exposure are established risk factors for premature birth and an independent risk factor for cerebral palsy. Both exert adverse effects on fetal development. In children with cerebral palsy, whether antenatal exposure to tobacco or alcohol is associated with a difference in clinical profile remains unknown. The Quebec Cerebral Palsy Registry was used to compare neurologic subtypes, gross motor functional impairment, and comorbidities in children with cerebral palsy who were or were not prenatally exposed to alcohol or tobacco. Information on in utero exposure was available in 249 children with cerebral palsy born from 1999-2002, of whom 77 were exposed to alcohol and 62 to tobacco in utero. No association was evident between exposure to tobacco or alcohol during pregnancy and neurologic subtype, Gross Motor Function Classification System score, mean number of comorbidities experienced, or each of eight comorbidities explored. Adjusting for prematurity or low birth weight exerted no effect on these results. In utero exposure to tobacco or alcohol does not assist in predicting clinical profiles of cerebral palsy.