Girl-Boy Twins with Developmental Delay from 16p11.2 Triplication due to Biparental Inheritance from Two Parents with 16p11.2 Duplication.

The 16p11.2 duplication is a well-known cause of developmental delay and autism, but there are only 2 previously reported cases of 16p11.2 triplication. Both of the previously reported cases exhibited tandem triplication on a 16p11.2 duplication inherited from 1 parent. We report fraternal twins presenting with developmental delay and 16p11.2 triplication resulting from inheritance of a 16p11.2 duplicated homolog from each parent. This report also reviews the overlapping features in previously published cases of 16p11.2 triplication, and possible implications are discussed.

Mechanical Thrombectomy in Pediatric Stroke: Report of Three New Cases.

BACKGROUND: Mechanical thrombectomy for treatment of arterial ischemic stroke (AIS) and cerebral venous thrombosis (CVT) is well-studied in adult populations, but not in children. METHODS: We report 3 new cases of pediatric stroke treated using mechanical thrombectomy. Two cases of AIS and 1 case of CVT were identified from 2018 pediatric stroke clinic records. RESULTS: Thrombectomy was successful in 1 of the 2 AIS cases and in the CVT case. None of the children were asymptomatic after thrombectomy. One AIS case had good recovery than developed dystonia which responded to treatment; the second AIS case had residual hemiplegia; and the child with CVT had mild school problems. CONCLUSIONS: Mechanical thrombectomy is being increasingly used for pediatric stroke treatment. This study and recent literature reviews suggest thrombectomy holds promise as a treatment for selected pediatric stroke patients. Questions remain about the safety and efficacy of thrombectomy in children with stroke since large randomized controlled studies are not yet feasible.

A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami.

Alazami syndrome is a rare autosomal recessive neurodevelopmental disorder due to loss-of-function variants in the La ribonucleoprotein 7 (LARP7) gene. Children with Alazami syndrome are most often affected by a combination of primordial dwarfism, intellectual disability, and distinctive facial features. Previous cases have been primarily found in consanguineous families from the Middle East, Asia, and North Africa. We present a 21-month-old Caucasian male from the Midwest United States with nonconsanguineous parents who presented with frequently reported findings of unusual facial features, poor growth, cardiac and genitourinary findings, and developmental delay; less-frequently reported findings, including transient erythroblastopenia of childhood (TEC) and immune deficiency; and never-before reported findings of periventricular nodular heterotopia and stroke. He developed stroke during a hospitalization for Hemophilus influenzae meningitis. The possible contributions of LARP7 to TEC, immune deficiency, brain malformation, and stroke are discussed. Guidelines for the care of Alazami patients are proposed.

A Standardized, 3-Tiered, Seizure Burden-Based Protocol for the Treatment of Neonatal Seizures.

OBJECTIVE: To evaluate use of a standardized, 3-tiered, seizure burden-based protocol for treatment of all electroencephalography (EEG)-confirmed seizures in a level IV neonatal intensive care unit (NICU). STUDY DESIGN: All infants admitted to the NICU with EEG-confirmed seizures over a 25-month period were enrolled in the study. We compared short-term outcomes before and after implementation of a standardized, 3-tiered protocol. RESULTS: A total of 107 infants were enrolled in the study. Use of midazolam infusions was reduced by 53.7% (p = 0.02). Midazolam infusion duration increased from 4 to 7.5 days (p = 0.003); however, when excluding 3 outliers, there was no significant difference between groups (-p = 0.67). Duration of EEG monitoring decreased from 5 to 3 days (p = 0.005). Hospital length of stay was unchanged. CONCLUSION: Implementation of a standardized, 3-tiered protocol for treatment of neonatal seizures improved short-term outcomes. Although not measured directly, reductions in EEG duration and midazolam use are promising indicators of overall seizure burden. More research is needed to evaluate impact on long-term neurodevelopmental outcomes.

Fetal Cerebral Sinovenous Thrombosis and Dural Sinus Malformation.

BACKGROUND: Fetal cerebral sinovenous thrombosis (CSVT) and dural sinus malformation (DSM) are rare types of fetal cerebral venous pathology that are becoming increasingly recognized as fetal imaging advances. Fetal DSMs are a common source of fetal CSVT, although CSVT may occur without a DSM. The literature on these disorders is limited. METHODS: Cases of fetal CSVT and DSM were identified retrospectively through a query of the Indiana University Health fetal imaging archive from 2007 to 2021. RESULTS: Seven cases were identified, all of whom were alive at birth. A DSM was present in six. Treatments after birth included enoxaparin sodium (3), embolization (3), and shunt placements (1). Five cases had documented regression or complete resolution of the thrombus and/or malformation. One was lost to follow-up, one died from complications of hydrocephalus at nine months, one was receiving physical and occupational therapy at last follow-up at three months, one had concern for autism and mild gait abnormality at 21 months, two had concern for speech delay (18 months and 24 months), and one had normal development at most recent follow-up (four years). CONCLUSIONS: Positive short-term outcomes may occur for some cases of fetal CSVT and DSM. However, risk factors and best treatments are not clear, and long-term outcome data are limited. There is a need for further study.

High-Dose Prednisolone for Treatment of Infantile Spasms After Presumed Perinatal Stroke.

ABSTRACT: BACKGROUND: High-dose prednisone and prednisolone have been increasingly studied as a lower-cost alternative to adrenocorticotropic hormone for the treatment of infantile spasms, but this treatment has not been well studied in children with infantile spasms due to perinatal stroke. METHODS: We identified a girl with new-onset infantile spasms due to presumed perinatal left middle cerebral artery stroke seen in our hospital's pediatric stroke clinic in 2019. RESULTS: This girl developed infantile spasms at 9 months old. She had right hemiplegic cerebral palsy due to her perinatal stroke but had been otherwise previously healthy. Modified hypsarrhythmia was confirmed on prolonged video-electroencephalography. High-dose prednisolone at 8 mg/kg per day was initiated on the sixth day of spasms. She was treated with this dose for 2 weeks and then tapered over 5 weeks. The girl became seizure-free after receiving her first dose of prednisolone and experienced no significant adverse effects during therapy. Routine electroencephalography after completion of prednisolone taper confirmed resolution of modified hypsarrhythmia and no epileptiform discharges. She continued to make excellent development progress during and after treatment. CONCLUSION: This case suggests high-dose prednisolone could be considered for first-line therapy for children with infantile spasms due to perinatal stroke; further study is needed.

Patients With Extreme Early Onset Juvenile Huntington Disease Can Have Delays in Diagnosis: A Case Report and Literature Review.

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy.

UNLABELLED: Golomb MR, McDonald BC, Warden SJ, Yonkman J, Saykin AJ, Shirley B, Huber M, Rabin B, AbdelBaky M, Nwosu ME, Barkat-Masih M, Burdea GC. In-home virtual reality videogame telerehabilitation in adolescents with hemiplegic cerebral palsy. OBJECTIVE: To investigate whether in-home remotely monitored virtual reality videogame-based telerehabilitation in adolescents with hemiplegic cerebral palsy can improve hand function and forearm bone health, and demonstrate alterations in motor circuitry activation. DESIGN: A 3-month proof-of-concept pilot study. SETTING: Virtual reality videogame-based rehabilitation systems were installed in the homes of 3 participants and networked via secure Internet connections to the collaborating engineering school and children's hospital. PARTICIPANTS: Adolescents (N=3) with severe hemiplegic cerebral palsy. INTERVENTION: Participants were asked to exercise the plegic hand 30 minutes a day, 5 days a week using a sensor glove fitted to the plegic hand and attached to a remotely monitored videogame console installed in their home. Games were custom developed, focused on finger movement, and included a screen avatar of the hand. MAIN OUTCOME MEASURES: Standardized occupational therapy assessments, remote assessment of finger range of motion (ROM) based on sensor glove readings, assessment of plegic forearm bone health with dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), and functional magnetic resonance imaging (fMRI) of hand grip task. RESULTS: All 3 adolescents showed improved function of the plegic hand on occupational therapy testing, including increased ability to lift objects, and improved finger ROM based on remote measurements. The 2 adolescents who were most compliant showed improvements in radial bone mineral content and area in the plegic arm. For all 3 adolescents, fMRI during grip task contrasting the plegic and nonplegic hand showed expanded spatial extent of activation at posttreatment relative to baseline in brain motor circuitry (eg, primary motor cortex and cerebellum). CONCLUSIONS: Use of remotely monitored virtual reality videogame telerehabilitation appears to produce improved hand function and forearm bone health (as measured by DXA and pQCT) in adolescents with chronic disability who practice regularly. Improved hand function appears to be reflected in functional brain changes.

The Impact of Pediatric Basal Ganglia Stroke on Mental Health in Children: Report of 2 Cases.

BACKGROUND: The impact of basal ganglia stroke on mental health is better described in adults than in children. We report 2 children with significant mental health issues after basal ganglia stroke. CASE REPORTS: Patient 1, an 8-year-old boy, had mild anxiety before his left basal ganglia stroke. Post-stroke, he developed severe anxiety, obsessions, depression, and attention deficit hyperactivity disorder, in addition to a right hemiplegia and some mild chorea. He gradually improved over 3 years with psychiatric care and medication but continued to have residual symptoms. Patient 2, a 10-year-old boy, had no history of mental health issues before his right basal ganglia stroke. Post-stroke, he developed significant anxiety and mild depression, along with a left hemiplegia. He improved over 9 months and returned to his mental health baseline. CONCLUSIONS: Mental health issues after basal ganglia stroke in children can be significant, and recovery can take months to years.

Bow Hunter's Syndrome in Children: A Review of the Literature and Presentation of a New Case in a 12-Year-Old Girl.

BACKGROUND: Bow hunter's syndrome, or occlusion of the vertebral artery with head rotation leading to ischemia and sometimes stroke, is rarely described in children. The authors review the literature and present a new case. METHODS: Both OVID dating back to 1946 and PubMed records were reviewed using the terms ("Bow hunter syndrome" OR "bow hunter's") OR "rotational vertebral artery occlusion" combined with "child," and limited to English language. SCOPUS and the bibliographies of cases found in the search were used to identify additional articles. RESULTS: Twelve articles were found describing 25 patients; there were 26 patients when combined with our case. Ages ranged from 1 to 18 years. Most (88.5%, 23/26) were male. Medical treatments included aspirin, clopidogrel, abciximab, enoxaparin, warfarin, and cervical collar. Stenting was tried in 2 cases but did not work long-term. Surgical treatments included decompression, cervical fusion, or a combination. We present a new case of a 12-year-old girl with recurrent stroke who had bilateral vascular compression only visible on provocative angiographic imaging with head turn. She was referred for cervical fusion, and abnormal ligamentous laxity was noted intraoperatively. CONCLUSIONS: Bow hunter's syndrome is a rare but important cause of stroke since many of the patients experience recurrent strokes before the diagnosis is made. Reasons for the male predominance are unclear. Provocative angiography plays a key role in diagnosis, and both medical treatment and neurosurgical intervention may prevent recurrence.

Male predominance in childhood ischemic stroke: findings from the international pediatric stroke study.

BACKGROUND AND PURPOSE: Previous studies suggested a male predominance in childhood ischemic stroke, mirroring gender differences in adults but were limited by small sample sizes or unconfirmed diagnoses. We sought to study gender within a large international series of confirmed cases of pediatric ischemic stroke. METHODS: From January 2003 to July 2007, the International Pediatric Stroke Study enrolled children (0 up to 19 years) with arterial ischemic stroke or cerebral sinovenous thrombosis at 30 centers in 10 countries. Neonates were those <29 days of age. We calculated the "expected" gender ratio for our study as the weighted average of population-based childhood gender ratios in enrolling countries weighted by the number of subjects enrolled in each country. chi(2) tests were used to compare the observed gender ratios in our series with this expected ratio (51.7%). RESULTS: Among 1187 children with confirmed ischemic stroke, 710 were boys (60%, P<0.0001). Male predominance persisted after stratification by age (61% for neonates, P=0.011; 59% for later childhood, P=0.002) and stroke subtype (58% for arterial ischemic stroke, P=0.004; 65% for cerebral sinovenous thrombosis, P=0.002). The greatest proportion of males occurred among children with arterial ischemic stroke and a history of trauma (75%, P=0.008), although boys were also overrepresented among those with arterial ischemic stroke and no trauma (57%; P=0.07). There were no gender differences in case fatality or deficits at discharge. CONCLUSIONS: Childhood ischemic stroke appears to be more common in boys regardless of age, stroke subtype, or history of trauma. Further exploration of this gender difference could shed light on stroke mechanisms in both children and adults.

Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young.

PURPOSE: The purpose of this statement is to review the literature on childhood stroke and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are responsible for diagnosing and treating infants, children, and adolescents with cerebrovascular disease. METHODS: The Writing Group members were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee. The panel included members with several different areas of expertise. Each of the panel's recommendations was weighted by applying the American Heart Association Stroke Council's Levels of Evidence grading algorithm. After being reviewed by panel members, the manuscript was reviewed by 4 expert peer reviewers and by members of the Stroke Council Leadership Committee and was approved by the American Heart Association Science Advisory and Coordinating Committee. We anticipate that this statement will need to be updated in 4 years. RESULTS: Evidence-based recommendations are provided for the prevention of ischemic stroke caused by sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and cardiogenic embolism. Recommendations on the evaluation and management of hemorrhagic stroke also are provided. Protocols for dosing of heparin and warfarin in children are suggested. Also included are recommendations on the evaluation and management of perinatal stroke and cerebral sinovenous thrombosis in children.

Cerebral palsy after perinatal arterial ischemic stroke.

The frequency of cerebral palsy, degree of disability, and predictors of disability were assessed in children in a perinatal arterial stroke database. Risk factors were assessed at the univariate level using the Pearson chi(2) and Fisher exact test and at the multivariate level using logistic regression analysis. Seventy-six of 111 children with perinatal stroke (68%) had cerebral palsy, most commonly hemiplegic (66/76; 87%). Multivariate analysis of the entire cohort showed both delayed presentation (OR,9.96; 95% CI, 3.10-32.02) and male sex (OR, 2.55; 95% CI, 1.03-6.32) were associated with cerebral palsy. In subgroup multivariate analyses: in children with neonatal presentation, bilateral infarcts were associated with triplegia or quadriplegia (OR, 5.33; 95% CI, 1.28-22.27); in children with unilateral middle cerebral artery infarcts, delayed presentation (OR, 10.60; 95% CI, 2.28-72.92) and large-branch infarction (OR, 8.78; 95% CI, 2.18-43.67) were associated with cerebral palsy. These data will aid physicians in planning long-term rehabilitative care for children with perinatal stroke.

West nile poliomyelitis in a 7-year-old child.

West Nile poliomyelitis is a well-described neurologic manifestation of West Nile viral infection in adults. However, few reports have described this manifestation in children infected with West Nile virus. We describe a 7-year-old boy who developed West Nile poliomyelitis with flaccid paralysis of his left leg. Electrodiagnostic testing and radiologic imaging confirmed anterior horn cell injury. We report on his course clinically and electrodiagnostically over 20 months.

Very early arterial ischemic stroke in premature infants.

Early stroke in the premature infant has rarely been described. Presented here are the cases of 23 infants, born between 23 and 35 weeks gestational age, with focal arterial ischemic stroke occurring before 44 weeks gestational age. Ten (43%) were male. Five children (22%) were half of a twin pair; no co-twin died. The most commonly affected territory was the middle cerebral artery territory. Three children with extreme prematurity (< or =26 weeks) had cerebellar infarcts. Twelve children had unilateral or bilateral intraventricular hemorrhages (grade 3 or higher in 8 of the 12). Twelve children had white matter injury: periventricular leukomalacia, hypoxic-ischemic encephalopathy, or both. Most children had multiple comorbidities, and the median neonatal intensive care unit stay was 63 days (range, 14-365). One child died in the neonatal intensive care unit (age 123 days). All 22 survivors were left with disabilities. Seventeen (77%) had cerebral palsy, 10 (45%) had epilepsy, and 17 (77%) had cognitive impairment. Arterial ischemic stroke appears to add to the neurologic disabilities commonly associated with prematurity.

Neonatal sinovenous thrombosis: presentation and association with imaging.

Few studies have examined when children with neonatal sinovenous thrombosis come to medical attention, risk factors associated with time of presentation, what clinical presentations are more likely to occur early or late, or whether the timing of presentation or severity of clinical presentation correlate with radiographic findings. Chi-square and Fisher's exact tests were used to explore associations in a cohort of 59 neonates with sinovenous thrombosis. Most (66%) came to medical attention within 48 hours of birth (defined as early presentation). Most (88%) had multiple comorbidities. Respiratory distress (P = 0.005), hypoxia (P = 0.02), poor tone (P = 0.05), fetal distress (P < 0.001), preterm delivery (P = 0.044), and low Apgar score (P = 0.018) were associated with early presentation. Infant dehydration was associated with late presentation (P < 0.001). Time of presentation was not associated with radiographic severity. Presentation with difficult-to-control seizures was marginally associated with hemorrhage (P = 0.096) but no other measure of radiographic severity. Neonates with sinovenous thrombosis often present within 48 hours, with multiple comorbidities and presenting signs, some of which are associated with time of presentation. Neither timing of presentation nor presence or absence of severe seizures can be used to predict findings on radiographic imaging.

Neuropsychologic outcomes in a case series of twins discordant for perinatal stroke.

Perinatal stroke may affect cognitive development, but few studies have addressed the details of cognitive function after perinatal stroke. The present study was designed to compare the neuropsychologic features of five sets of twins discordant for perinatal stroke. All of the affected children had unilateral middle cerebral artery infarction (two left, three right); four of the five infarcts were large-branch, affecting the entire M1 territory. Three of the five affected children had comorbid epilepsy. Measures of intelligence, memory, language, attention, executive function, visual-motor integration, and fine motor skills were administered to children at a median age of 5 years (range, 5-8 years). Relative to their unaffected co-twins, the twins with perinatal stroke exhibited lower levels of full scale (p=0.005), verbal (p=0.006), and nonverbal (p=0.005) intelligence. Children with perinatal stroke also showed significant deficits on tests of verbal memory (p=0.041), receptive language (p=0.011), verbal fluency (p=0.019), and visual attention (p=0.011), compared with their unaffected co-twins. Twin gestation may be a risk factor for poor cognitive outcome after perinatal stroke. Large infarct size and comorbid epilepsy may have contributed to some of the poor cognitive outcomes in this cohort.