Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BACKGROUND: Neonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy. METHODS: This is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy. RESULTS: In a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1ß pathway were significantly associated with epilepsy. CONCLUSIONS: Elevations in pro-inflammatory cytokines in the IL-1ß pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers.

Pediatric neuropalliative care.

Pediatric palliative care seeks to support quality of life for children and families affected by serious illness. Children with neurological disease are among the most frequent recipients of pediatric palliative care. Several important elements distinguish pediatric palliative care from adult practice, including a longer illness duration, longitudinal relationships over the span of years, diseases characterized by chronic fragility rather than progressive pathology, and the reliance on parents as proxy decision makers. This chapter will provide an overview of pediatric neuropalliative care, with emphasis on the types of disease trajectories, symptom management, and communication principles for supporting shared decision making with families. The role of neurology expertise is highlighted throughout, with special attention toward incorporating palliative care into pediatric neurology practice.

Designing successful virtual residency interviews: a survey-based needs assessment of applicants across medical specialties.

Background: Residency selection in the United States relied on in-person interviews for many decades. The COVID-19 pandemic and recommendations from the Coalition for Physician Accountability (COPA) required programs to implement virtual interviews for the 2020-2021 residency selection cycle. Although virtual interviews may become the norm in the future, there is scant data at the institutional level to inform how to best approach this process. Objective: To describe the perceptions of applicants to several residency programs at one institution on the importance of virtual recruitment features and assess the impact on their overall ranking decisions. Methods: Applicants who interviewed for 12 medical and surgical residency programs during the 2020-2021 cycle at the University of California San Francisco were invited to participate in an anonymous survey in March 2021, after all interviews were completed. A survey consisting of 26 questions was administered to applicants on features that are important during interviews and the impact on their ranking decisions scored on a 5-point Likert scale. Results: Of the 1422 participating applicants, 303 (21%) completed the survey. The most important feature for applicants during the interview day was getting a feel of the program (92%). Conversations with residents (91%) and faculty (79%) were also highly rated. Respondents reported morale and happiness of residents (71%) as an extremely important factor in their overall ranking decision. Conclusion: Programs should consider prioritizing features that aid in alignment with getting to know residents and faculty and provide a sense of morale over emphasis on the institutional and location features. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-022-00004-5.

Acute Fulminant Cerebral Edema: A Newly Recognized Phenotype in Children With Suspected Encephalitis.

BACKGROUND: Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted. METHODS: All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases. RESULTS: Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1-18 years) and 8.0 years (0.5-18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen.Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described. CONCLUSIONS: AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition.

Characterization of Death in Neonatal Encephalopathy in the Hypothermia Era.

This study aimed to characterize the circumstances of death in encephalopathic neonates treated with therapeutic hypothermia. Patients who died after or during treatment with therapeutic hypothermia between 2007-2014 were identified. Patient circumstance of death was characterized using an established paradigm. Thirty-one of 229 patients died (14%) at a median of 3 days of life. Most who died were severely encephalopathic on examination (90%) and had severely abnormal electroencephalographic (EEG) findings (87%). All those who had magnetic resonance images (n = 13) had evidence of moderate-severe brain injury; 6 had near-total brain injury. Cooling was discontinued prematurely in 61% of patients. Most patients (90%) were physiologically stable at the time of death; 81% died following elective extubation for quality of life considerations. Three patients (10%) died following withholding or removal of artificial hydration and nutrition. Characterization of death in additional cohorts is needed to identify differences in decision making practices over time and between centers.

Delayed presentation of tetraparesis following posterior thoracolumbar spinal fusion and instrumentation for adolescent idiopathic scoliosis.

STUDY DESIGN: Case report. OBJECTIVE: We present a case of delayed tetraparesis in a patient after posterior spinal fusion for adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The reported rate of neural complications after scoliosis surgery is low. Intraoperative neuromonitoring is used to detect and prevent spinal cord injury. METHODS: Review of medical record. RESULTS: Delayed tetraparesis developed on the second postoperative day after unremarkable T3-L4 posterior fusion. MRI revealed evidence of cord ischemia at C4-C7. Angiogram revealed a hypervascular T4 body resulting in arteriovenous shunting into the epidural venous plexus. CONCLUSION: Venous congestive myelopathy due to arteriovenous shunting or unrecognized syrinx are presented as possible etiologies of this patient's spinal cord injury. A preoperative MRI may have helped discern the cause of this patient's spinal cord injury.

Neonatal encephalopathy in the term infant: neuroimaging and inflammatory cytokines.

The interrelationship between inflammation and ischemia is complex and poorly understood in the developing nervous system. In the preterm newborn, maternal infection may predispose to white matter injury and may be associated with cytokine elevation. In the term infant, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. This review discusses the interplay among inflammatory cytokines, neonatal encephalopathy, and neuroimaging parameters.

Neonatal encephalopathy: association of cytokines with MR spectroscopy and outcome.

In term neonatal encephalopathy, little is known about the relationship between early inflammatory markers, neonatal brain injury, and long-term neurodevelopmental outcome. Our goal was to determine whether neonatal serum cytokine levels are associated with cerebral metabolism assessed by proton magnetic resonance spectroscopy (MRS), with magnetic resonance imaging (MRI) abnormalities, and with neurodevelopmental outcome at 30 mo of age. Levels of seven cytokines [IL-1 beta, IL-6, IL-8, IL-9, IL-12, IL-13, and tumor necrosis factor (TNF)-alpha] were measured in dried neonatal blood by immunoaffinity chromatography in a prospective cohort of 62 term newborns at risk of neonatal encephalopathy. MR images (n = 61) were scored and lactate/choline and N-acetyl-aspartate (NAA)/choline were measured by MRS (n = 42) on median day of life 6 in the deep gray nuclei (DGN) and in the watershed/cortical zone (WS). Neurodevelopmental outcome (n = 54) was considered abnormal if the infant died or if cognitive delay and/or functional motor deficit were detected at 30 mo. IL-1 beta, IL-6, IL-8 and TNF-alpha were significantly associated with lactate/choline in the DGN (p = 0.03, 0.02, 0.03, and 0.01 respectively), but not in the WS (all p > 0.1). Cytokines were not associated with NAA/choline in any region or with MRI scores. Children with abnormal neurodevelopmental outcome had higher neonatal levels of IL-1 beta, IL-6, IL-8, and lower levels of IL-12 (p = 0.04, 0.03, 0.01, 0.03 respectively). Elevated inflammatory cytokines were associated with impaired cerebral oxidative metabolism, but not with detectable MRI changes in the neonatal period. Understanding the link between elevated cytokines and outcome would inform novel strategies of cerebral protection.