Exome sequencing (ES) became clinically available in 2011 and promised an agnostic, unbiased next-generation sequencing (NGS) platform for patients with symptoms believed to have a genetic etiology. ...The diagnostic yield of ES has been estimated to be between 25–40% and may be higher in specific clinical scenarios. Those who remain undiagnosed may have no molecular findings of interest on ES, variants of uncertain significance in genes that are linked to human disease, or variants of uncertain significance in candidate genes that are not definitively tied to human disease. Recent evidence suggests that a post-exome evaluation consisting of clinical re-phenotyping, functional studies of candidate variants in known genes, and variant reevaluation can lead to a diagnosis in 5–15% of additional cases. In this brief research study, we present our experience on post-exome evaluations in a cohort of patients who are believed to have a genetic etiology for their symptoms. We have reached a full or partial diagnosis in approximately 18% (6/33) of cases that have completed evaluations to date. We accomplished this by utilizing NGS-based methods that are available on a clinical basis. A sample of these cases highlights the utility of ES reanalysis with updated phenotyping allowing for the discovery of new genes, re-adjudication of known variants, incorporating updated phenotypic information, utilizing functional testing such as targeted RNA sequencing, and deploying other NGS-based testing methods such as gene panels and genome sequencing to reach a diagnosis.
A previously published, single-institution, case series suggested an association between topiramate administration in neonates and subsequent development of necrotizing enterocolitis (NEC). This ...contradicted our more extensive experiences using topiramate in this population. We therefore studied safety and tolerability of topiramate for treating refractory neonatal seizures, hypothesizing that the risk of developing NEC following topiramate exposure was low and that most infants tolerate topiramate.
This multicenter retrospective cohort study included seventy-five neonates who received topiramate to treat seizures from January 2011 to October 2019 at three geographically diverse level IV neonatal intensive care units affiliated with pediatric tertiary hospitals. Data included demographics, birth history, seizure etiology, treatment response, side effects, and occurrence and details of NEC.
Three of seventy-five infants (4%) developed NEC following topiramate exposure. These infants did not differ in gestational age, birth weight, seizure etiology, postmenstrual age, weight when topiramate was initiated, or dosing of topiramate. Topiramate was well tolerated. Only three infants (4%) discontinued due to side effects. The most common side effect (20%) was weight loss (typically <5%). Topiramate was felt to be efficacious (61%). Most infants (72%) continued topiramate when discharged.
Our multicenter, 75-infant study demonstrated that development of NEC after treatment with topiramate was rare (4%) and refutes prior literature suggesting an association. Topiramate was felt to be efficacious and was well tolerated. Although limited by retrospective design, study data are broadly applicable and support thoughtful use of topiramate as a safe, reasonable option for treating refractory neonatal seizures.
We report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient.
A previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis.
This is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.
Acute flaccid myelitis is an emerging neurologic disease, first described in 2014 and predominantly affecting young children. Acute flaccid myelitis cases tend to spike every 2 years, in the late ...summer to fall, and the next peak is expected in 2020. The diagnosis of acute flaccid myelitis is often delayed, leading to suboptimal evaluation, including incomplete laboratory assessment. Acute and chronic morbidity are high, and a standardized, multidisciplinary approach to evaluation and treatment is essential to optimizing outcomes. In a review of acute flaccid myelitis patients treated in 2018 at our institution, we noted considerable variability in days to presentation, evaluation, and treatment. In response, the authors developed a protocol for the evaluation and management of pediatric patients suspected of having acute flaccid myelitis. The protocol was developed using local experience/case review, expert consensus, and the relevant literature. The protocol spans the spectrum of care, from initial evaluation in a primary care or emergency setting, to acute hospital management and evaluation and long-term inpatient and rehabilitation settings. The purpose of this report is both to share the findings from our 2018 case review and to disseminate our acute flaccid myelitis protocol. Our hope is that publication of our protocol will both inform the development of a standardized approach to acute flaccid myelitis and to encourage other centers to form a multidisciplinary acute flaccid myelitis team to provide expert care throughout the disease process, from presentation to recovery.
Prior studies have demonstrated a pediatric epilepsy readmission rate of 6% to 10% but have not described details of the readmitted patients. We report the characteristics of pediatric patients ...admitted for epilepsy who were readmitted to the hospital within 30 days of discharge.
An interdisciplinary team was established to individually review and characterize the 30-day readmissions of patients admitted for epilepsy from May 2014 to October 2016. The team contained both inpatient and outpatient neuroscience nurses, care managers, a quality outcomes manager, and child neurology physicians.
Over a 30-month period we had an all-cause 30-day readmission rate of 8.0%, which was 219 pediatric epilepsy readmissions from 169 patients. We found that 21.5% of readmissions were scheduled, 37% were for progression of chronic epilepsy, 9.6% were for recently diagnosed epilepsy, and 14.6% were for unrelated diagnoses. We classified 21.5% of readmissions as preventable and 64.9% as not preventable. Thirty-five percent of readmissions occurred within seven days of the initial discharge, including 29 of 47 (61.7%) preventable readmissions. The most common reasons for preventable readmissions were problems with the discharge care plan or medication management.
We demonstrate that 21.5% of pediatric epilepsy readmissions were scheduled and 21.5% were judged to be preventable. The majority of preventable readmissions occurred within seven days of index discharge. Characterizing epilepsy readmissions is the first step in being able to reduce readmissions.
BACKGROUNDWe report the clinical, radiological, laboratory, and neuropathological findings in support of the first diagnosis of lethal, small-vessel cerebral vasculitis triggered by severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric patient. PATIENT DESCRIPTIONA previously healthy, eight-year-old Hispanic girl presented with subacute left-sided weakness two weeks after a mild febrile illness. SARS-CoV-2 nasopharyngeal swab was positive. Magnetic resonance imaging revealed an enhancing right frontal lobe lesion with significant vasogenic edema. Two brain biopsies of the lesion showed perivascular and intraluminal lymphohistiocytic inflammatory infiltrate consistent with vasculitis. Despite extensive treatment with immunomodulatory therapies targeting primary angiitis of the central nervous system, she experienced neurological decline and died 93 days after presentation. SARS-CoV-2 testing revealed positive serum IgG and positive cerebrospinal fluid IgM. Comprehensive infectious, rheumatologic, hematologic/oncologic, and genetic evaluation did not identify an alternative etiology. Postmortem brain autopsy remained consistent with vasculitis. CONCLUSIONThis is the first pediatric presentation to suggest that SARS-CoV-2 can lead to a fatal, postinfectious, inflammatory small-vessel cerebral vasculitis. Our patient uniquely included supportive cerebrospinal fluid and postmortem tissue analysis. While most children recover from the neurological complications of SARS-CoV-2, we emphasize the potential mortality in a child with no risk factors for severe disease.
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