Journal of Child Neurology最新文献

Introduction16p11.2 microdeletion syndrome is a rare genetic condition with wide clinical heterogeneity. Individuals may present a normal phenotype or neurodevelopmental pathology, often associated with nonspecific dysmorphology, epilepsy, cardiac anomalies and obesity, among other characteristics.Clinical CasesCase 1: Male, 11-year-old, with macrocephaly from 4 months, obesity from 2 years, and speech delay; currently diagnosed with intellectual developmental disorder. Case 2: Female, 13-year-old, referred at 4 years due to language delay; at 6 years, early puberty and obesity were identified; currently recognized as having intellectual developmental disorder and attention-deficit hyperactivity disorder (ADHD). Case 3: Male, 5-year-old, referred at 3 years for global developmental delay, mainly in language; family history of intellectual developmental disorder; currently has global developmental delay. Case 4: Male, 6-year-old, referred at 11 months for motor delay; at 18 months, language delay, motor coordination difficulties, and aggressiveness were noted; recently, he was diagnosed with autism spectrum disorder. Case 5: Male, 14-year-old, with macrocephaly and expressive language delay at 2 years; oppositional behavior and ADHD diagnosed, with learning disabilities and overweight. None of the cases have epilepsy or cardiac pathology. All showed 16p11.2 microdeletion in array-CGH studies and received multidisciplinary follow-up.Discussion/Conclusion16p11.2 microdeletion syndrome shows significant clinical variability, with common neurodevelopmental involvement. Genetic testing via array-CGH helps establish the etiologic diagnosis, making it essential for individuals with global developmental delay / intellectual developmental disorder or autism spectrum disorder. Early diagnosis enables timely intervention and genetic counseling.

Agenesis of the corpus callosum (ACC) has a wide spectrum of anatomic manifestations associated with incompletely understood clinical variability. In this retrospective cohort study, 161 children with ACC were classified into complete ACC and partial ACC. Partial and complete ACC diagnoses were confirmed by postnatal magnetic resonance imaging (MRI) and further classified as isolated or complex (associated with other brain abnormalities or genetic diagnoses). Clinical characteristics, clinical outcomes, and co-occurring genetic variations were collected by chart review. Median age at last neurologic evaluation for the complete and partial ACC cohorts were 2.8 years and 2.3 years, respectively; thus, an average of 2-3 years of follow-up data were analyzed per patient. Results showed that children with complete and partial ACC had similar birth characteristics. Children with complete ACC were more frequently diagnosed prenatally; additionally, complete ACC patients had lower rates of cerebral palsy. When comparing complex complete ACC and complex partial ACC to isolated complete ACC and isolated partial ACC, respectively, the complex subcohorts had a higher level of motor delay, assistive device use, cerebral palsy, ventriculoperitoneal shunt placement, epilepsy, language delay, and cognitive delay than the isolated subcohorts. About 50% of children had genetic variants associated with neurodevelopmental disorders in this cohort. Additionally, >50% of our patients with motor and nonmotor developmental delays, as well as >60% of patients that required assistive devices and had cerebral palsy, were also found to have genetic anomalies. Although research describing ACC and its outcomes is expanding, there is still a need for large cohort studies with robust follow-up data to help further understand the disease.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative condition that rapidly progresses with language regression, loss of ambulation, blindness, intractable seizures, and premature death in childhood. Enzyme replacement therapy has transformed the clinical trajectory of CLN2 disease, and early genetic testing is crucial because enzyme replacement therapy cannot reverse clinical progression. Lack of clinician awareness of early clinical symptomatology, initially normal language development, and history of provoked or treatment-responsive seizures may contribute to diagnostic and treatments delays. There remain challenges in equitable enzyme replacement therapy access globally and implementation of dual treatment to address retinopathy. There is a need to better understand the phenotype of CLN2 disease in the era of enzyme replacement therapy, including children who receive treatment presymptomatically. Gene therapy is a promising curative treatment, notwithstanding the mixed clinical evidence on efficacy and challenges achieving widespread brain transgene expression. This review explores our current understanding of early clinical presentation of CLN2 disease, epilepsy phenotype, role of genetic testing, novel biomarkers, and precision treatments including enzyme replacement therapy.

The negative impact of the Social Determinants of Health (SDOH) on health care outcomes in vulnerable populations, particularly pediatric patients, is a well-established phenomenon. The treatment of traumatic brain injury is not an exception. It is not clear, however, which specific social determinants of health factor is more influential on the current management of traumatic brain injury in these populations. This study addresses this gap by exploring how these factors influence the treatment of traumatic brain injuries in pediatric patients at Boston Medical Center, a safety net hospital in Boston, MA. Our hypothesis suggests that the presence of some of the social determinants of health negatively affects the treatment of traumatic brain injury in children and youth. Through a χ² test of independence conducted on 247 patients, analyzing variables such as insurance status, primary language, race, ethnicity, and zip code, we demonstrated a lack of statistically significant evidence of a relationship between the identified social determinants of health and treatment completion status.

Fentanyl is a potent opioid anesthetic and analgesic whose illicit use has been linked to a significant increase in mortality and morbidity, affecting not only adults but also children through accidental exposure. We present a case of a 12-month-old normally developing baby girl who was admitted for hypothermia, acute hypoxic respiratory failure, altered mental status, and metabolic acidosis. A comprehensive workup confirmed the presence of fentanyl in her urine. A magnetic resonance image (MRI) of the brain revealed multiple areas of signal abnormalities in the subcortical and periventricular white matter. The infant recovered and was discharged with an age-appropriate neurologic examination. A repeat MRI at 18 months showed almost complete resolution of the previous findings along with a normal neurologic exam and development for age. This case emphasizes the importance of timely diagnosis and appropriate management in preventing long-term neurologic sequelae associated with fentanyl exposure.

In the past 2 decades, the rates of autism spectrum disorder and assisted reproductive technology have increased significantly, leading to a controversial discussion regarding their association. This study investigates the possible association between assisted reproductive technology and autism spectrum disorder using a case-control design, comparing 319 children diagnosed with autism spectrum disorder from 2013 to 2020 with 319 age-matched typically developing children followed prospectively from birth. The differences between assisted reproductive technology and spontaneous conception were analyzed between groups, adjusting for gender, types of assisted reproductive technology, and severity of autism. As expected, there is male predisposition in the autism group. The rate of assisted reproductive technology use in the autism spectrum disorder group (8.5%) was not significantly different from that in typically developing children (9.4%). Within the autism spectrum disorder group, the conception via assisted reproductive technology did not substantially influence gender distribution or severity of autism in comparison to spontaneous conception. After adjusting for potential confounders, the odds ratio for assisted reproductive technology treatment was not statistically significant (adjusted odds ratio [aOR] = 0.537, 95% confidence interval [CI] 0.110-3.383). Similarly, no significant association was found for hormonal treatment (aOR = 0.632, 95% CI 0.326-1.223) or for in vitro fertilization pregnancies (aOR = 0.689, 95% CI 0.180-2.628). In conclusion, assisted reproductive technology was not found to be more common in children with autism spectrum disorder as compared to typically developing children and did not correlate with gender or autism severity within the autism spectrum disorder group. Our findings effectively counter the concerns regarding a significant association between assisted reproductive technology and autism and provide reassurance.

In data from a multicenter prospective observational study, we assessed whether interictal epileptiform discharge metrics in the pre-seizure onset surveillance scalp electroencephalograms (EEGs) in children with tuberous sclerosis complex could predict seizure outcomes, specifically epileptic spasms. In 16 children with eligible EEG data (7 with epileptic spasms and 9 with other seizure types) and 16 controls, 2 spike metrics were calculated through automated detection followed by expert review: (1) spike rate (spikes per minute) and (2) number of unique spike foci. In patients who developed seizures, a combination of spike rate threshold of ≥2 per minute and ≥2 unique spike foci during sleep was highly predictive of impending epileptic spasms (100% positive predictive value, 2 false negatives). One control patient was falsely predicted to develop epileptic spasms, decreasing the overall positive predictive value to 83.3%. These findings suggest that EEG spike metrics could predict impending epileptic spasms in children with tuberous sclerosis complex, pending larger-scale validation.

Reversible cerebral vasoconstriction syndrome (RCVS) is uncommon in childhood. Although it usually has favorable outcomes, it still carries a risk of serious complications, including intracranial bleeding and ischemic stroke. RCVS may arise idiopathically, from vasoactive triggers or from daily activities such as defecation, urination, exertion, or sexual activity. Whole-body cryotherapy (WBC) is not officially recognized as a trigger for RCVS. We present a case of RCVS in an adolescent who underwent a WBC session preceding his symptoms and diagnosis. Although an association between cold weather exposure and stroke is recognized, the connection between cold weather and RCVS is less established. Furthermore, there is limited to no evidence linking WBC to stroke or RCVS. We aim to highlight a potential side effect of WBC, an increasingly popular intervention lacking evidence-based benefits and well-studied side effects.