Youssef, Paul E.

Importance Rapid whole-genome sequencing (WGS) has advanced inpatient genetic diagnosis, although most evidence comes from neonatal and pediatric intensive care unit (ICU) populations. Its utility for pediatric neurology inpatients across broader acute settings remains insufficiently established. Objective To assess the diagnostic yield, clinical impact, and factors associated with phenotype-concordant rapid WGS diagnoses. Design, Setting, and Participants This was a retrospective cohort study conducted from June 1, 2022, through January 17, 2026, at a tertiary medical center. Pediatric inpatients in the neonatal ICU, pediatric ICU, or general floor with an unexplained neurologic presentation were included. Those with established nongenetic etiology were excluded from analyses. Exposures Trio (77.8%), duo (9.1%), or singleton (13.1%) rapid WGS. Main Outcomes and Measures The primary outcome was the initial phenotype-concordant diagnostic yield at the point of care. Secondary outcomes were reanalysis yield (new diagnoses from reinterpreting nondiagnostic cases prompted by a new unexplained phenotype or family request), cumulative yield, and management change. Associations were assessed by logistic regression (odds ratios [ORs] and 95% CIs). Results Among 175 children (median [IQR] age, 4 months [1 day-4 years]; 93 male [53.1%]) who met inclusion criteria (82 neonates, 93 nonneonates), initial rapid WGS established a phenotype-concordant diagnosis in 79 (45.1%), higher in nonneonates (49 of 93 [52.7%]) than neonates (30 of 82 [36.6%]). Preliminary results returned at mean (SD) 4.0 (1.6) days and final reports at 10.4 (4.5) days. Positive nonconcordant findings occurred in 33 children (18.9%). Reanalysis of 14 nondiagnostic cases yielded 3 additional diagnoses, for a cumulative yield of 82 of 175 children (46.9%). Most diagnoses were monogenic (63 [76.8%]). Management changed in 54 of 82 phenotype-concordant cases (65.9%; 53 at the point of care, 1 after reanalysis) and 8 of 33 (24.2%) positive nonconcordant cases. Family history was most strongly associated with diagnosis (adjusted OR [aOR], 6.46; 95% CI, 3.23-12.93; P < .001), followed by multisystem involvement (aOR, 2.85; 95% CI, 1.24-6.54; P = .01) and congenital anomaly or dysmorphism (aOR, 2.47; 95% CI, 1.07-5.68; P = .03). Hypotonia was most strongly associated in neonates (OR, 20.63; 95% CI, 5.46-77.87; P < .001); ICU admission (OR, 10.25; 95% CI, 2.79-37.67; P < .001) predominated in nonneonates. Conclusions and Relevance Results of this cohort study suggest that rapid WGS diagnosed nearly half of pediatric neurology inpatients and changed management in two-thirds of diagnosed cases, supporting its potential use as early diagnostic testing. Associated features may guide patient selection, and reanalysis extends yield longitudinally.

Alice in Wonderland syndrome is a disorienting perceptual disorder characterized by discrete episodes of bizarre visual illusions and spatial distortions which has been associated with numerous neurologic and psychiatric conditions. Little is known regarding the electrophysiologic correlates of the visual symptoms described in this syndrome. The authors report the unique case of an 8-year-old boy presenting with visual distortions consistent with Alice in Wonderland syndrome, and an electroencephalogram demonstrating bilateral temporo-occipital slowing which correlated with symptoms of micropsia, teleopsia, and dysmorphopsia. Identification of this clinical syndrome and its electroclinical features are important for establishing a proper diagnosis and subsequent reassurance or appropriate treatment directed toward the underlying etiology.

Migraine is the most common acute and recurrent headache syndrome in children. This condition has unique clinical characteristics in the pediatric population, that can evolve with age, and significantly impact a child's quality of life, affecting their education, socialization, and family life. The purpose of this review is to describe the varied clinical features of migraine seen in children, and discuss potential treatment options for pediatric migraine, including chronic migraine. In many patients a multifaceted approach involving lifestyle changes, treatment of comorbid conditions, and pharmacological treatments are needed for optimal headache control.What this paper adds Migraine presents as various phenotypes in children, sometimes evolving as the child ages. An expanded range of treatment options exists for the challenging chronic migraine patient.

The cause and treatment of functional movement disorders and nonepileptic spells in children is poorly understood, and an association with migraine has not previously been reported. We retrospectively reviewed children diagnosed with chronic or episodic migraine at our institution from 2006 to 2013 to determine the proportion with nonorganic movement disorders, their phenomenology, provoking factors, and natural history. Thirty-two patients were identified, representing 4.3% of patients with chronic migraine and 0.9% of patients with episodic migraine. Twenty-four of the 32 (75%) had chronic migraine, whereas 8 (25%) had episodic migraine. Nonepileptic spells was the most common phenomenon in both cohorts, followed by tremor and functional gait disorders. Severe migraine attacks preceded these movements in the majority of patients. With appropriate migraine therapy, significant reduction or resolution of these movements was reported. We conclude that nonorganic movement disorders are observed in pediatric migraine, are more prevalent among chronic migraineurs, and can resolve with improved pain control.