Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study.

BACKGROUND: Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. METHODS: The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT). RESULTS: Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3-12 months, with 50-100% sensitivity. CONCLUSIONS: Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention. IMPACT: The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life. Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD). Brain MRI at 3 or 12 months can confirm KSD. The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD. The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

Examining diagnostic variability among pediatric subspecialists using case examples of infant head injury.

BACKGROUND: Although there is research regarding the diagnosis and timing of abusive head trauma, there remains practice variation among pediatric subspecialists. OBJECTIVES: To examine diagnostic variability among pediatric subspecialists using case examples of infant head injury. Secondary objectives were timing variability among subspecialists, and diagnostic and timing variability among Child Abuse Pediatricians (CAPs). PARTICIPANTS AND SETTING: Pediatric subspecialists were recruited from Child Abuse Pediatrics, Hospital Medicine, Emergency Medicine, Critical Care, and Neurosurgery to complete a research instrument. Participants qualified for the study if they evaluated at least 1 case of possible abusive head trauma during their career. METHODS: This multi-institutional, mixed-methods study used a research instrument with 4 case examples of infant head injury: severe retinal hemorrhages (RH), mass-effect subdural hemorrhage (SDH), SDH membrane formation, and sepsis. The response selected by most CAPs was reference and compared across subspecialties and among CAPs using Chi-square or Fisher's exact tests. A Bonferroni correction (p < 0.01) was used for subspecialty comparisons. RESULTS: There were 288 participants who completed at least 1 case example. Diagnostic variability was observed in all case examples. Significantly fewer Hospital Medicine (34.9 % vs. 57.9 %, p < 0.01), Emergency Medicine (28.0 % vs. 57.9 %, p < 0.0001), and Neurosurgery (24.0 % vs. 57.9 %, p < 0.01) participants selected the reference response for the mass-effect SDH case example. Timing variability was statistically significant for all case examples (p < 0.01). Significantly fewer CAPs aged 44-64 years selected the reference response for timing (p < 0.01) for the severe RH case example. CONCLUSIONS: Additional peer review processes and consensus guidelines for challenging issues in abusive head trauma may be beneficial.

Internal carotid artery position to characterize risk for vessel injury in pediatric intraoral trauma.

OBJECTIVE: The internal carotid artery (ICA) lies in close anatomic proximity to the oropharynx and is at risk for injury in the instance of intraoral trauma. The objectives of this study are to describe the position of the ICA relative to the oropharynx and identify patient risk factors related to its position. METHODS: A total of 100 patients aged 12 months to 7 years 11 months who received computed tomography (CT) of the neck were randomly selected. The position of the ICA was determined by measuring its angular location relative to the center of the oropharynx (ICA angle) and the shortest distance from the oropharyngeal surface (OP-ICA distance). RESULTS: Indication for imaging was controlled for in all reported data. Patient age was related to ICA angles on both the left (F = 8.06; P = 0.01; η2 = 0.08, 95% CI: 0.01-0.19) and right (F = 18.62; P < 0.001; η2 = 0.17, 95% CI: 0.05-0.29). Patient weight also was related to ICA angles on both the left (F = 7.08; P = 0.01; η2 = 0.07, 95% CI: 0.01-0.18) and right (F = 11.86; P < 0.001; η2 = 0.11, 95% CI: 0.02-0.24). Patient age was related to the left OP-ICA distance (F = 7.36; P = 0.01; η2 = 0.07, 95% CI: 0.01-0.19), as was patient weight (F = 4.82; P = 0.03; η2 = 0.05, 95% CI: 0.00-0.15). Across all measurements, no significant relationship was identified between ICA position and other patient variables, including sex and race/ethnicity. CONCLUSION: The ICA of younger patients and those with lower body weight may be located more medially within the neck and closer to the oropharyngeal surface. This vessel position may place these children at greater anatomic susceptibility for ICA injury in the event of intraoral trauma.

Next-Generation Sequencing in the Diagnosis of Rare Pediatric Sinonasal Tumors.

The diagnosis of desmoid fibromatosis or other spindle cell tumors in the sinonasal region is very rare in children and needs to be thoroughly confirmed with immunohistochemical and/or molecular tests. We report 2 patients with such rare tumors and describe the use of next-generation sequencing in their evaluation. A 3-year-old female had a 4.4-cm midline nasal cavity mass involving the bony septum and extending into the base of the skull bilaterally. The moderate cellular fibroblastic proliferation revealed areas of thick keloid-like collagen bands and other areas with myxoid edematous stroma. Deep targeted sequencing identified a novel G34V mutation in the CTNNB1 gene consistent with desmoid fibromatosis. An 11-month-old male infant presented with a right nasal mass that extended through the cribriform plate into the anterior cranial fossa and involved the right ethmoid sinus and adjacent right orbit. Histology revealed an infiltrative atypical fibrous proliferation with focal calcifications that was negative for CTNNB1 and GNAS mutations. A novel RET E511K variant was identified in the tumor and later was also found in the germline and hence rendered of unknown significance. Both cases highlight the utility of next-generation sequencing in the evaluation of pediatric sinonasal spindle cell tumors that may have overlapping pathologic features. Reporting of rare or novel variants in tumor-only sequencing should be cautiously evaluated in children and pairing with germline sequencing may be needed to avoid the pitfall of assigning uncommon variants.

A ten-year retrospective evaluation of acute flaccid myelitis at 5 pediatric centers in the United States, 2005-2014.

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics. METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged ≤18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate. RESULTS: At 5 sites combined, 26 AFM cases were identified from 2005-2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p<0.0001). A cluster of 13 cases was identified in September-October 2014 (temporal scan p = 0.0001). No other temporal or seasonal trend was observed. Compared with cases from January 2005-July 2014 (n = 29), cases from August-December 2014 (n = 15) were younger (p = 0.002), more frequently had a preceding respiratory/febrile illness (p = 0.03), had only upper extremities involved (p = 0.008), and had upper extremity monoplegia (p = 0.03). The cases had higher WBC counts in cerebrospinal fluid (p = 0.013). CONCLUSION: Our data support emergence of AFM in 2014 in the United States, and those cases demonstrated distinctive features compared with preceding sporadic cases.

Osmotic Demyelination Syndrome in Children.

Osmotic demyelination syndrome is an acute demyelination process that usually occurs several days following an osmotic stress. This syndrome is rare in adults (0.4% to 0.56%) and even more uncommon in children. We performed a review of all reported pediatric osmotic demyelination syndrome patients from 1960 to 2018. Among all 106 cases, 49 presented with isolated central pontine myelinolysis, 30 with isolated extrapontine myelinolysis, and 27 with combined central pontine myelinolysis and extrapontine myelinolysis. There was no gender preponderance, and the highest prevalence was noted between the ages one and five years. Magnetic resonance imaging remains the diagnostic modality of choice, and diffusion tensor imaging is now increasingly used for prognostication in osmotic demyelination syndrome. Sixty percent of the children had a complete neurological recovery. Current management of osmotic demyelination syndrome in children consists of supportive medical care, steroids, and intravenous immunoglobulin. Our review of the literature supports the hypothesis that steroids and immunoglobulins are potentially helpful, although additional controlled studies are needed.

Pre-Surgical Planning: Multimodality Imaging to Optimize Outcomes in Pediatric Epilepsy Surgery.

Neuroimaging is an important component of the pre-surgical planning for pediatric epilepsy. High-resolution structural magnetic resonance images are combined with advanced structural and functional imaging techniques to better define the surgical lesion and decrease morbidity postoperatively. The combination of neuroimaging, electroencephalography (EEG), and neuropsychiatric testing in a multidisciplinary epilepsy conference setting is essential for determining a plan for surgical management.

Evaluations for abuse in young children with subdural hemorrhages: findings based on symptom severity and benign enlargement of the subarachnoid spaces.

OBJECTIVE Children who have subdural hematomas (SDHs) with no or minimal neurological symptoms (SDH-mild symptoms) often present a forensic challenge. Nonabusive causes of SDH, including birth-related SDH, benign enlargement of the subarachnoid spaces (BESS), and other proposed causes have been offered as etiologies. These alternative causes do not provide explanations for concomitant suspicious injuries (CSIs). If SDH with mild symptoms in young children are frequently caused by these alternative causes, children with SDH-mild symptoms should be more likely to have no other CSIs than those who have SDH with severe symptoms (SDH-severe symptoms). Additionally, if SDH with mild symptoms is caused by something other than abuse, the location and distribution of the SDH may be different than an SDH caused by abuse. The objectives of this study were to determine the prevalence of other CSIs in patients who present with SDH-mild symptoms and to compare that prevalence to patients with SDH-severe symptoms. Additionally, this study sought to compare the locations and distributions of SDH between the two groups. Finally, given the data supporting BESS as a potential cause of SDH in young children, the authors sought to evaluate the associations of BESS with SDH-mild symptoms and with other CSIs. METHODS The authors performed a 5-year retrospective case-control study of patients younger than 2 years of age with SDH evaluated by a Child Abuse Pediatrics program. Patients were classified as having SDH-mild symptoms (cases) or SDH-severe symptoms (controls). The two groups were compared for the prevalence of other CSIs. Additionally, the locations and distribution of SDH were compared between the two groups. The presence of BESS was evaluated for associations with symptoms and other CSIs. RESULTS Of 149 patients, 43 presented with SDH-mild symptoms and 106 with SDH-severe symptoms. Patients with SDH-mild symptoms were less likely to have other CSIs (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.08-0.5) and less likely to have severe retinal hemorrhages (OR 0.08, 95% CI 0.03-0.3). However, 60.5% of patients with SDH-mild symptoms had other CSIs. There was no difference between the groups regarding the location and distribution of SDH. Of the entire study cohort, 34 (22.8%) had BESS, and BESS was present in 17 (39.5%) of the SDH-mild symptoms group and 17 (16%) of the SDH-severe symptoms group (OR 3.4, 95% CI 1.5-7.6). The presence of BESS was significantly associated with a lower chance of other CSIs (OR 0.1, 95% CI 0.05-0.3). However, 17 patients had BESS and other CSIs. Of these 17, 6 had BESS and SDH-mild symptoms. CONCLUSIONS The high occurrence of other CSIs in patients with SDH-mild symptoms and a similar high occurrence in patients with BESS (including those with SDH-mild symptoms) indicate that such children benefit from a full evaluation for abuse.

Evaluation of the Hypothesis That Choking/ALTE May Mimic Abusive Head Trauma.

OBJECTIVE: Apparent life-threatening events (ALTEs), often accompanied by choking, have been hypothesized to cause subdural hemorrhages (SDH), retinal hemorrhages, and brain injury. If the choking/ALTE hypothesis were true, children who present with ALTE and SDH would have fewer extracranial injuries suspicious for abuse than those with SDH and no ALTE. We aimed to compare the prevalence of suspicious extracranial injuries in children who have ALTE-associated SDH to those with non-ALTE SDH. METHODS: We performed a 5-year retrospective case-control study of children <2 years of age with SDH evaluated by the Child Abuse Pediatrics program at a children's hospital. Subjects were classified as ALTE-associated SDH and non-ALTE SDH on the basis of ALTE definitions as proposed by the authors of the choking/ALTE hypothesis. The 2 groups were compared for the prevalence of suspicious extracranial injuries. RESULTS: Of 170 study subjects, 64 had an ALTE-associated SDH and 106 had non-ALTE SDH. ALTE-associated SDH subjects were nearly 5 times more likely to have at least one suspicious extracranial injury (odds ratio [OR] 4.8, 95% confidence interval [CI] 1.9-12.1) and were more likely to have individual types of suspicious extracranial injuries, including retinoschisis (OR 4.1, 95% CI 1.6-10.2), high-specificity bruising (OR 2.6, 95% CI 1.3-4.9), and internal abdominal injury (3.5, 95% CI 1.2-9.9). Subjects with ALTE-associated SDH were also significantly more likely to die or have persistent neurologic impairment. All 10 subjects with a dysphagic-choking type ALTE had at least 1 suspicious extracranial injury. CONCLUSIONS: ALTEs are not supported as causative mechanisms for findings concerning abusive head trauma.

Clival osteomyelitis resulting from spread of infection through the fossa navicularis magna in a child.

The fossa navicularis is a notch-like bone defect in the basiocciput that has been hitherto considered as an anatomical variant of the clivus and not previously described as a potential source of clival or skull base pathology. We report the imaging findings in a 5-year-old child who presented acutely with a retropharyngeal abscess and osteomyelitis of the clivus. Imaging after treatment revealed a "notch-like" defect in the anterior clivus consistent with a fossa navicularis. Based on these appearances, we postulate that the lymphoid tissue of the pharyngeal tonsil residing in the fossa navicularis served as a route through which infection spread and subsequently developed into clival osteomyelitis, which is a rare diagnosis. This case is unique, and we believe that the presence of this variant in young children may be important and is not merely an anatomical curiosity.