Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid.

In January 2019, a new plant-derived purified cannabidiol preparation, approved by the US Food and Drug Administration, became commercially available for patients ≥2 years old with Lennox-Gastaut syndrome or Dravet syndrome. Among our patients who were prescribed the new cannabidiol formulation, we observed several cases of thrombocytopenia and therefore embarked on this study. We conducted a single-center systematic chart review of all pediatric patients (<21 years old) who were prescribed cannabidiol from January to August 2019. We evaluated salient features of the patients' epilepsy syndrome, age, concurrent medications, and surveillance laboratory results before and after cannabidiol initiation. Among 87 patients, nine (10%) developed thrombocytopenia (platelet nadir range = 17 000-108 000) following initiation of cannabidiol. Each of these nine children was on combination therapy of cannabidiol with valproic acid. Whereas no children on cannabidiol without valproic acid (0/57) developed thrombocytopenia, nine of 23 treated with combination valproic acid and cannabidiol developed platelets < 110 000/µL (P < .0001). We report a novel and clinically important side effect of thrombocytopenia in one-third of patients treated concurrently with cannabidiol and valproic acid. If this finding is confirmed, clinicians should perform close monitoring for thrombocytopenia when adding cannabidiol to a regimen that includes valproic acid.

A Review of the Impact of Sociodemographic Factors on the Assessment and Management of Pediatric Somatic Symptom and Related Disorders.

BACKGROUND: While factors such as race, sex, gender identity, and socioeconomic status impact the diagnosis and treatment of a variety of conditions, there are few studies examining their influence on somatic symptom and related disorders (SSRDs), particularly in the pediatric population. OBJECTIVE: In this review, we outline the existing literature on how sociodemographic characteristics influence the overall care of pediatric SSRDs. Throughout this literature review, we highlight opportunities for further research, including potential disparities in evaluation, management, and outcomes along several sociodemographic domains. METHODS: We conducted a thorough review of the evidence for potential impact of race, sex, gender identity, and socioeconomic status on the presentation, diagnosis, management, and outcomes of pediatric somatization and SSRDs. RESULTS: Recent studies evaluating the impact of race on SSRD care suggest the potential for provider bias in the evaluation and management of this population based on racial differences in diagnostic evaluations. Somatization may present differently based on a patient's race and potential cross-cultural status. Among studies of cisgender patients, there is evidence of provider bias in the assessment of somatic symptoms such that female patients are more likely to be diagnosed with an SSRD than male patients. However, there is little research among youth identifying as LGBTQ. The literature also indicates that low socioeconomic status and associated stressors are linked with the development of SSRDs, although it is unclear whether these factors are subject to bias by providers. CONCLUSIONS: While the literature is sparse, there is evidence that sociodemographic factors contribute to differences in diagnosis, evaluation, and management of pediatric SSRDs. These factors, particularly race and sex, may also be subject to provider bias, although further studies are necessary. Provider bias can directly impact patients' perception of care, including feelings of dismissal, and may have downstream influences on symptom manifestation, patient-provider engagement, diagnostic evaluation, and management practices.

Taking the Pain out of Somatization: Development and Implementation of a Hospital-Based Clinical Practice Guideline to Address Pediatric Somatic Symptom and Related Disorders.

OBJECTIVES: The diagnostic category of somatic symptom and related disorders (SSRDs), although common, is often poorly recognized and suboptimally managed in inpatient pediatric care. Little literature exists to address SSRDs in the inpatient pediatric setting. The purpose of the study was to characterize current SSRD practice, identify problem areas in workflow, and develop a standardized approach to inpatient evaluation and management at a tertiary care academic children's hospital. METHODS: A multidisciplinary group identified patients with SSRD admitted between May 2012 and October 2014. A retrospective chart review on a convenience sample was performed to identify population characteristics and current practice. Lean methodology was used to define current state practice and future state intervention. These methods were used to guide identification of problem areas, which informed protocol, a clinical practice guideline, and resource development. RESULTS: Thirty-six patients aged 8 to 17 years met inclusion criteria for chart review. Most patients presented with either neurologic or pain-related complaints. The mean length of stay was 5.44 days (SD = 6.3), with few patients receiving a mental health consultation within 24 hours of hospitalization. Patients averaged 5.8 medical and/or psychiatric diagnoses on discharge (SD = 5.2), and two-thirds did not have an SSRD diagnosis. Half of patients had comorbid psychiatric diagnoses, whereas one-quarter were discharged with no mental health follow-up. CONCLUSIONS: In this study, we describe the process and content development of a single-site institutional protocol, clinical practice guideline, and resources for the evaluation and management of pediatric SSRDs. This study may serve as a model for similar standardization of SSRD care in other inpatient pediatric medical settings.

Pediatric Somatic Symptom and Related Disorders: Primary Care Provider Perspectives.

Somatization, or physical symptoms that are inconsistent with a physiological cause that may or may not involve an identified stressor, is common in outpatient pediatrics. When these symptoms persist, they can impair function and progress to a somatic symptom and related disorder (SSRD), resulting in increased health care use and increased demands on primary care providers (PCPs). We performed a needs assessment among PCPs to better understand how best to support providers caring for children with SSRDs. Pediatric PCPs (n = 77) were surveyed to better understand their training, experience, perceptions, and practices of SSRD care. Findings indicate that PCPs have limited training in SSRD care but express interest in learning more. Many barriers to effective care were reported. We hope to use these findings to develop training materials and support services for pediatric PCPs managing SSRDs.

Infantile spasms as a cause of acquired perinatal visual loss.

BACKGROUND: Visual abnormalities have been described in patients with infantile spasms (IS), an epileptic syndrome of early childhood. METHODS: We report on 3 children who exhibited cortically mediated visual regression in association with the development of IS. RESULTS: In 1 patient, loss of visual behavior was the presenting complaint. In all patients, visual behavior improved with treatment of seizures. CONCLUSIONS: IS are a potentially treatable cause of cortically impaired vision in early childhood. Because visual behavior might improve when the seizures are treated, patients should be referred appropriately.

Subdural hemorrhages associated with antithrombotic therapy in infants with cerebral atrophy.

Low-molecular-weight heparins, such as enoxaparin, are often used to treat thrombosis in infants. We present 4 infants with diffuse brain injury who developed cerebral venous sinus thrombosis or deep vein thrombosis and were treated with enoxaparin. These infants subsequently developed subdural hemorrhages, and enoxaparin was stopped. In 3 cases, the subdural hemorrhages were found on routine surveillance brain MRI, and in 1 case imaging was urgently obtained because of focal seizures. Two patients needed urgent neurosurgical intervention, and all subdural hemorrhages improved or resolved on follow-up imaging. Each infant developed severe neurologic deficits, probably from the coexisting diffuse brain injury rather than from the subdural hemorrhages themselves. The risk of intracranial hemorrhage from enoxaparin may be accentuated in patients with diffuse brain injury, and careful consideration should be given before treatment in this population.

Leigh syndrome in a girl with a novel DLD mutation causing E3 deficiency.

We present the biochemical and molecular diagnosis of dihydrolipoamide dehydrogenase deficiency (also known as E3 deficiency) and Leigh syndrome in a 14-year-old girl with learning disability and episodic encephalopathy and ketoacidosis. The diagnosis was based on values of plasma amino acids and urine organic acids, obtained during acute encephalopathy, lactic ketoacidosis, and liver failure, precipitated by infectious mononucleosis. Enzymatic and molecular analyses confirmed dihydrolipoamide dehydrogenase deficiency. E3 activity from cultured skin fibroblasts ranged from 9-29% of the mean. Molecular analysis revealed compound heterozygosity for novel and known pathogenic mutations (p.I353T and p.G136del, respectively). The patient received dietary augmentation and continuous renal replacement therapy, given her severe, persistent lactic acidosis. Acute decompensation resulted in magnetic resonance imaging changes involving the posterior aspect of the putamen, lateral, and medial thalami, substantia nigra, lateral geniculate bodies, and splenium of the corpus callosum. The cortex and subcortical white matter of the right and left occipital lobes and perirolandic region were also affected. In our review of molecularly confirmed patients with dihydrolipoamide dehydrogenase deficiency, Leigh syndrome was common. Our patient, whose most severe decompensation occurred at a more advanced age than previously reported, provides further evidence of the heterogeneous presentations of dihydrolipoamide dehydrogenase deficiency.