Presenting Patterns of Genetically Determined Developmental Encephalopathies With Epilepsy and Movement Disorders: A Single Tertiary Center Retrospective Cohort Study.

Background: This paper aimed to evaluate the frequency of observation of genetically determined developmental encephalopathies with epilepsy and movement disorders in a specialistic center, the distribution of etiologies and presenting clinical hallmarks, and the mean times for the achievement of molecular genetic diagnosis. Patients and Methods: Retrospective data about clinical phenotypes, etiology, and diagnostic pathways were collected in all the genetically confirmed patients with developmental encephalopathies with epilepsy and movement disorders referred to our institution between 2010 and 2020. The cohort was divided into two groups according to the predominant movement disorder type: 1) Group A: patients with hyperkinetic movement disorders; 2) Group B: patients with hypokinetic movement disorders. Both groups were analyzed in terms of developmental, epileptic, and movement disorder phenotypes. Results: The cohort included 69 patients (Group A = 53; Group B = 16). The etiological spectrum was heterogeneous with a predominance of Rett and Angelman syndrome in Group A and neurodegenerative disorders in Group B. A moderate/severe intellectual disability was assessed in 58/69 patients (mean age at the first signs of developmental impairment = 1,87 ± 1,72 years). Group A included patients with an earlier onset of epileptic seizures (2,63 ± 3,15 vs. 4,45 ± 5,55 years of group B) and a predominant generalized motor semiology of seizures at the onset. Focal seizures were the main initial epileptic manifestations in Group B. Seizures were noticed earlier than movement disorders in Group A while the opposite occurred in Group B. A higher increase in molecular genetic diagnosis was obtained in the last five years. Mean diagnostic delay was longer in Group B than in Group A (12,26 ± 13,32 vs. 5.66 ± 6.41 years). Chorea as an initial movement disorder was associated with a significantly longer diagnostic delay and a higher age at etiological diagnosis. Conclusions: This study suggested: (a) a higher frequency of genetic defects involving neurotransmission, neuronal excitability, or neural development in patients with hyperkinetic movement disorders; (b) a higher frequency of neurodegenerative courses and a longer diagnostic delay in patients with hypokinetic movement disorders.

Loss of Continuity of Care in Pediatric Neurology Services during COVID-19 Lockdown: An Additional Stressor for Parents.

Background. This study aimed to investigate the consequence of the COVID 19-related lockdown on the well-being of children with neurological and neurodevelopmental disorders and the repercussion on parental stress during the period 9 March 2020-3 May 2020. Methods. A web-based survey was shared via mail with the parents of children affected by chronic neurologic disorders and neurodevelopmental disorders in the continuity of care in two Italian tertiary centers, independently by the severity of the diseases and the required frequency of controls. For each patient, they were asked to identify a single main caregiver, among the two parents, to fill in the questionnaire. Parental stress was measured via the Perceived Stress Scale (PSS). Statistical analysis was performed with IBM SPSS Statistics version 25. The differences between the clinical groups were performed with one way ANOVA. The dimensional effect of the clinical variables on outcome was evaluated by multiple linear regression analysis. Results. The survey was completed by 250 parents (response rate = 48.9 %). Sars-Cov2 infection was reported in two patients only. A total of 44.2% of the patients had completely interrupted school activities while 70% of parents underwent changes in their job modalities. Health care services were disrupted in 77% of patients. Higher PSS scores were detected in the parents of children with neurodevelopmental disorders (p = 0.035). Conclusions. The loss of continuity of care during the lockdown must be considered as a risk factor for parents caring for children with chronic neurologic diseases and neurodevelopmental disorders in further phases of the current pandemic.

Sleep terrors-A parental nightmare.

Sleep terrors (STs) are sleep disorders characterized by abrupt arousal from sleep with autonomic hyperactivity and inappropriate behavior. Though a common condition in childhood that usually affects children between 4 and 12 years of age, STs, however, may be present even in adulthood. The exact etiology of STs is not known yet, however, several hypotheses have been proposed over the years, identifying some potential genetic, neurodevelopmental, or other causes. Nevertheless, a useful pathophysiological model identified a common cascade of predisposing, priming, and precipitating factors, which could help to explain and sometimes prevent STs. Establishing a correct diagnosis is mandatory for appropriate management, as several conditions (such as other parasomnias or nocturnal seizures) may mimic STs. Furthermore, we also described some conditions which can be comorbid to STs, like some medical or psychological disorders. A number of treatment options have been proposed, ranging from only sleep hygiene practices to pharmacological therapies; we reviewed some of the most prominent ones. In spite of the fact that STs have long been considered benign disorders, which tend to reduce spontaneously over the years, they may have unexpected consequences on the child but also on the caregivers.

The relation between sleep and neurocognitive development in infancy and early childhood: A neuroscience perspective.

Sleep is essential for human life. It has different characteristics in the early stages of life compared to later periods: during development, qualitative and quantitative changes in sleep features occur such as the onset of REM/NREM sleep at 3 months, the progressive increase of night sleep duration, and the reduction of total sleep time. Sleep seems to be essential in the cognitive functions' development, especially in the first period of life. Indeed, higher rates of night sleep at the age of 12 and 18 months are associated with higher executive functions' performance. Furthermore, memory consolidation occurs during sleep and sleep contributes to children's learning not only in retaining information but also in organizing memories most efficiently. Therefore, sleep problems could cause negative effects on some features of cognitive development like memory, executive functions, and learning process. There is also an intimate relationship between sleep and regulation of emotional brain functions, with a link between sleep disturbance and behavioral problems.

Update on the treatment of vitamin B6 dependent epilepsies.

Introduction: Vitamin B6 dependent epilepsies are a group of treatable diseases (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinaemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects) responding to pyridoxine or pyridoxal-5I-phosphate. Areas covered: A critical review was conducted on the therapeutic management of all the reported patients with genetically confirmed diagnoses of diseases affecting vitamin B6 metabolism and presenting with pyridoxine or pyridoxal-5I-phosphate dependent-seizures. Data about safety and efficacy were analyzed as well as the management of supplementation with pyridoxine or pyridoxal-5I-phosphate both in the acute phases and in the maintenance therapies. The authors also analyzed alternative therapeutic strategies for ALDH7A1 deficiency (lysine-restricted diet, arginine supplementation, oligonucleotide antisense therapy, upstream inhibition of aminoadipic semialdehyde synthase). Expert opinion: The administration of pyridoxine or pyridoxal-5I-phosphate should be considered in all intractable seizures also beyond the first year of life. Lysine restricted diet and arginine supplementation should be introduced in all the confirmed ALDH7A1 deficient patients. Pre or post-natal supplementation with pyridoxine should be given in familial cases until an eventual molecular genetic disconfirmation. Minor data about alternative therapies are available for other disorders of vitamin B6 metabolism.