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.

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.

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.

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.

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.

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.

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.

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.

Childhood Stroke and Vision: A Review of the Literature.

OBJECTIVE: Here we review the current literature regarding visual outcome after perinatal and childhood stroke. BACKGROUND: Visual deficits following stroke in adults are common and have been previously reviewed. Less is known about visual deficits following stroke in neonates and older children. Most of the literature regarding this subject has focused on preterm infants, or on other types of brain injury. This review summarizes the types of visual deficits seen in term infants following perinatal stroke and children following childhood stroke and predictors of outcome. This review suggests areas for future research. METHODS: We performed Ovid MEDLINE searches regarding visual testing in children, vision after childhood stroke, neuroplasticity of vision, treatment of visual impairment after stroke, and driving safety concerns after stroke. RESULTS: Visual field defects were the most commonly reported visual deficits after perinatal and childhood stroke. There is a significant lack of literature on this subject, and most is in the form of case reports and case series. Children can experience significant visual morbidity after stroke, and have the potential to show some recovery, but guidelines on assessment and treatment of this population are lacking. CONCLUSIONS: There were limitations to this study, given the small amount of literature available. Although stroke in children can result in severe visual deficits, most children regain at least a portion of their vision. However, more research is needed regarding visual assessment of this population, long-term visual outcomes, specific predictors of recovery, and treatment options.

Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome.

Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.

The Controversial Second Impact Syndrome: A Review of the Literature.

BACKGROUND: Second impact syndrome is a devastating injury that primarily affects athletic children and young adults. It occurs when a second concussion occurs before symptoms from the first concussion have resolved. Diffuse and often catastrophic cerebral edema results. Reports of second impact syndrome are few, and some argue that second impact syndrome is simply diffuse cerebral swelling unrelated to the first concussion. METHODS: Ovid and PubMed were searched from years 1946 to 2015 using the terms "second impact syndrome," "repeat concussion," and "catastrophic brain injury." In addition, review articles were found using a combination of the terms, "concussion," "second impact syndrome," and "repetitive head trauma." RESULTS: Seventeen patients in seven publications met the criteria of having two witnessed hits and persistent symptoms from the first to the second concussion. Ten of the 17 (59%) included individuals were football players. All were male. Ages ranged from 13 to 23 years. All children with poor outcomes (death or permanent disability) were younger than 20 years, while four of the five players with good outcomes were older than 19 years. The lag time from first to second concussion ranged from one hour to four weeks, and in many cases, at least one of the two hits appeared minor. CONCLUSIONS: American football, male gender, and young age appear to be associated with second impact syndrome. Controversies surrounding this syndrome are discussed. There is a need for prospective studies to clarify risk factors and outcomes of second impact syndrome to guide return-to-play recommendations for young athletes.

Spinal Cord Stroke Presenting With Acute Monoplegia in a 17-Year-Old Tennis Player.

BACKGROUND: Acute monoplegia is a rare presentation for spinal cord stroke, which usually presents with paraplegia or paraparesis. PATIENT DESCRIPTION: We describe an athletic girl who presented after a week of heavy athletic activity complaining of back and left leg pain, followed by flaccid left leg paralysis. RESULTS: The prothrombotic evaluation was unremarkable. Cerebrospinal fluid studies demonstrated elevated myelin basic protein but no oligoclonal bands. Magnetic resonance imaging revealed a lesion in the anterior cord from T9 to T11 with T2 hyperintensity, contrast enhancement, and diffusion restriction, suggesting infarction. There was a herniated disc at T10-T11 contacting the spinal cord and Schmorl's nodes at T11 and T12. Magnetic resonance angiography of the spinal cord was limited by movement artifact. CONCLUSIONS: The combination of our patient's clinical presentation, imaging studies, and laboratory evaluation suggests that our patient had a spinal cord infarct. A fibrocartilaginous embolism was the likely mechanism of infarct due to the presence of Schmorl's nodes and disc herniation on imaging. In addition to spinal cord stroke, other possible mechanisms leading to presentation with monoplegia, such as transverse myelitis, neuromyelitis optica, and multiple sclerosis, are discussed.