BACKGROUND:Medical student note writing is an important part of the training process but has suffered in the electronic health record (EHR) era as a result of student notes being excluded from the billable encounter. The 2018 CMS billing changes allow for medical student notes to be used for billable services provided that physical presence requirements are met, and attending physicians satisfy performance requirements and verify documentation. This has the potential to improve medical student engagement and decrease physician documentation burden.METHODS:Our institution implemented medical student notes as part of the billable encounter in August 2018 with support of our compliance department. Note characteristics including number, type, length, and time in note were analyzed before and after implementation. Rotating medical students were surveyed regarding their experience following implementation.RESULTS:There was a statistically significant increase in the number of student-authored notes following implementation. Attending physicians' interactions with student notes greatly increased following the change (4% of student notes reviewed vs. 84% of student notes). Surveyed students reported that having their notes as part of the billable record made their notes more meaningful and enhanced their learning. The majority of surveyed students also agreed that they received more feedback following the change.CONCLUSION:Medical students are interested in writing notes for education and feedback. Inclusion of their notes as part of the billable record can facilitate their learning and increase their participation in the note writing process.

PURPOSE:Despite evidence for macrostructural alteration in epilepsy patients later in life, little is known about the underlying pathological or compensatory mechanisms at younger ages causing these alterations. The aim of this work was to investigate the impact of pediatric epilepsy on the central nervous system, including gray matter volume, cerebral blood flow, and water diffusion, compared with neurologically normal children.METHODS:Inter-ictal magnetic resonance imaging data was obtained from 30 children with epilepsy ages 1-16 (73% F, 27% M). An atlas-based approach was used to determine values for volume, cerebral blood flow, and apparent diffusion coefficient in the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens. These values were then compared with previously published values from 100 neurologically normal children using a MANCOVA analysis.RESULTS:Most brain volumes of children with epilepsy followed a pattern similar to typically developing children, except for significantly larger putamen and amygdala. Cerebral blood flow was also comparable between the groups, except for the putamen, which demonstrated decreased blood flow in children with epilepsy. Diffusion (apparent diffusion coefficient) showed a trend towards higher values in children with epilepsy, with significantly elevated diffusion within the thalamus in children with epilepsy compared with neurologically normal children.CONCLUSION:Children with epilepsy show statistically significant differences in volume, diffusion, and cerebral blood flow within their thalamus, putamen, and amygdala, suggesting that epilepsy is associated with structural changes of the central nervous system influencing brain development and potentially leading to poorer neurocognitive outcomes.

OBJECTIVE:Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM).STUDY DESIGN:Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children's Hospital Stanford 1/1/2009-6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated.RESULTS:A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related.CONCLUSION:Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.

PurposeWith improved medical care, some individuals with holoprosencephaly (HPE) are surviving into adulthood. We investigated the clinical manifestations of adolescents and adults with HPE and explored the underlying molecular causes.MethodsParticipants included 20 subjects 15 years of age and older. Clinical assessments included dysmorphology exams, cognitive testing, swallowing studies, ophthalmic examination, and brain magnetic resonance imaging. Genetic testing included chromosomal microarray, Sanger sequencing for SHH, ZIC2, SIX3, and TGIF, and whole-exome sequencing (WES) of 10 trios.ResultsSemilobar HPE was the most common subtype of HPE, seen in 50% of the participants. Neurodevelopmental disabilities were found to correlate with HPE subtype. Factors associated with long-term survival included HPE subtype not alobar, female gender, and nontypical facial features. Four participants had de novo pathogenic variants in ZIC2. WES analysis of 11 participants did not reveal plausible candidate genes, suggesting complex inheritance in these cases. Indeed, in two probands there was a history of uncontrolled maternal type 1 diabetes.ConclusionIndividuals with various HPE subtypes can survive into adulthood and the neurodevelopmental outcomes are variable. Based on the facial characteristics and molecular evaluations, we suggest that classic genetic causes of HPE may play a smaller role in this cohort.

Electronic medical records (EMRs) are being rapidly adapted in the United States with goals of improving patient care, increasing efficiency, and reducing costs. Neurologists must become knowledgeable about the utility and effectiveness of the important parts of these systems specifically needed for care of neurology patients. The field of neurology encompasses complex disorders whose diagnosis and management heavily relies on detailed medical documentation of history and physical examination, and often on specialty-specific ancillary tests and extensive neuroimaging. Small discrepancies in documentation or absence of an in-hand ancillary test result can drastically change the current workup or treatment decision of a complex patient with neurologic disease. We describe current models and opportunities for improvements to EMRs that provide utility and efficiency in the care of neurology patients.

The Coffin–Lowry syndrome (CLS) is a rare but well-defined X-linked semidominant syndrome characterized by psychomotor and growth retardation, and progressive skeletal changes. CLS is caused by loss of function mutations in the Rps6ka3 gene encoding the ribosomal S6 kinase 2 (RSK2) protein. A distinctive paroxysmal disorder has been described in some CLS patients, characterized by episodes of sudden falling, without apparent alteration of consciousness, usually induced by unexpected tactile or auditory stimuli. Duration of episodes is very short, usually lasting a few seconds. The appellation "Stimulus-induced drop episodes" (SIDEs) was proposed for these non-epileptic events in CLS patients. SIDEs are clinically heterogeneous; with some patients exhibiting cataplexy-like events characterized by sudden hypotonia and collapse, and others hyperekplexia-like episodes with a startle response. The pathophysiology of SIDEs is not well understood.

Background: Online social networks (OSNs) are a new, promising approach for catalyzing health-related behavior change. To date, the empirical evidence on their impact has been limited. Purpose: Using a randomized trial, we assessed the impact of a health-oriented OSN with accelerometer and scales on participant’s physical activity, weight, and clinical indicators. Methods: A sample of 349 PeaceHealth Oregon employees and family members were randomized to the iWell OSN or a control group and followed for 6 months in 2010-2011. The iWell OSN enabled participants to connect with “friends,” make public postings, view contacts’ postings, set goals, download the number of their steps from an accelerometer and their weight from a scale, view trends in physical activity and weight, and compete against others in physical activity. Both control and intervention participants received traditional education material on diet and physical activity. Laboratory data on weight and clinical indicators (triglycerides, high-density lipoprotein, or low-density lipoprotein), and self-reported data on physical activity, were collected at baseline, 3 months, and 6 months. Results: At 6 months, the intervention group increased leisure walking minutes by 164% compared with 47% in the control group. The intervention group also lost more weight than the controls (5.2 pounds compared with 1.5 pounds). There were no observed significant differences in vigorous exercise or clinical indicators between the 2 groups. Among intervention participants, greater OSN use, as measured by number of private messages sent, was associated with a greater increase in leisure walking and greater weight reduction over the study period. Conclusions: The study provides evidence that interventions using OSNs can successfully promote increases in physical activity and weight loss.

Agenesis of the corpus callosum (ACC) is one of the more common brain malformations encountered by neonatologists and pediatricians. It may occur in isolation but more often is associated with other brain malformations. ACC also is a feature in >100 genetic syndromes. Fetal neuroimaging advances have allowed prenatal detection of callosal agenesis and associated anomalies in the brain and other organs. The outcome in ACC is varied and depends largely on the related anomalies and underlying etiology. This review discusses the etiologies and diagnosis of ACC and provides strategies for a more specific prenatal diagnosis, such as Aicardi and Zellweger syndromes.

Electronic physician documentation is an essential element of a complete electronic medical record (EMR). At Lucile Packard Children's Hospital, a teaching hospital affiliated with Stanford University, we implemented an inpatient electronic documentation system for physicians over a 12-month period. Using an EMR-based free-text editor coupled with automated import of system data elements, we were able to achieve voluntary, widespread adoption of the electronic documentation process. When given the choice between electronic versus dictated report creation, the vast majority of users preferred the electronic method. In addition to increasing the legibility and accessibility of clinical notes, we also decreased the volume of dictated notes and scanning of handwritten notes, which provides the opportunity for cost savings to the institution.

Little has been reported on fetal diagnosis of choroidal fissure cysts and prediction of the clinical complications that can result. We describe the case of a near-term male infant with prenatally diagnosed choroidal fissure cyst and bilateral clubfeet. His prolonged course in the neonatal intensive care nursery was marked by severe panhypopituitarism, late-onset diabetes insipidus, placement of a cystoperitoneal shunt, and episodes of sepsis. Postnatal genetic evaluation also revealed an interstitial deletion involving most of band 10q26.12 and the proximal half of band 10q26.13. The patient had multiple readmissions for medical and surgical indications and died at 6 months of age. This case represents the severe end of the spectrum of medical complications for children with choroidal fissure cysts. It highlights not only the importance of comprehensive evaluation and multidisciplinary management and counseling in such cases, but also the need for heightened vigilance in these patients.

Plasma exchange involves non-selectively removing plasma components that are potentially pathogenic in immune-mediated diseases from a patient's blood. Intravenous immunoglobulin used for therapeutic purposes are pooled human immunoglobulins derived from the plasma of 10000-100000 healthy donors. The major component of intravenous immunoglobulins (IVIg) preparations is IgG; very small amounts of other immunoglobulins, immunoglobulin fragments, and other smaller plasma proteins are also present. IVIg affect several components of the immune system and have been used successfully in the treatment of several neuroimmunological disorders. IVIg therapy has been evaluated both as a treatment of acute demyelinating relapses as well as a maintenance therapy to alter the disease course in adult patients with multiple sclerosis (MS). This chapter focuses on studies pertaining to the treatment of acute relapses. Plasma exchange might be an effective and relatively well-tolerated treatment option for severe demyelinating relapses in MS patients.

Holoprosencephaly (HPE), which results from failed or incomplete midline forebrain division early in gestation, is the most common forebrain malformation. The etiology of HPE is complex and multifactorial. To date, at least 12 HPE-associated genes have been identified, including TGIF (transforming growth factor beta-induced factor), located on chromosome 18p11.3. TGIF encodes a transcriptional repressor of retinoid responses involved in TGF-β signaling regulation, including Nodal signaling. TGIF mutations are reported in approximately 1–2% of patients with non-syndromic, non-chromosomal HPE.We combined data from our comprehensive studies of HPE with a literature search for all individuals with HPE and evidence of mutations affecting TGIF in order to establish the genotypic and phenotypic range. We describe 2 groups of patients: 34 with intragenic mutations and 21 with deletions of TGIF. These individuals, which were ascertained from our research group, in collaboration with other centers, and through a literature search, include 38 probands and 17 mutation-positive relatives. The majority of intragenic mutations occur in the TGIF homeodomain. Patients with mutations affecting TGIFrecapitulate the entire phenotypic spectrum observed in non-chromosomal, non-syndromic HPE. We identified a statistically significant difference between the 2 groups with respect to inheritance, as TGIF deletions were more likely to be de novo in comparison to TGIF mutations (χ2(2) = 6.97, ppermutated = 0.0356). In addition, patients with TGIF deletions were also found to more commonly present with manifestations beyond the craniofacial and neuroanatomical features associated with HPE (p = 0.0030). These findings highlight differences in patients with intragenic mutations versus deletions affecting TGIF, and draw attention to the homeodomain region, which appears to be particularly relevant to HPE. These results may be useful for genetic counseling of affected patients.

BACKGROUND: Implementations of computerized physician order entry (CPOE) systems have previously been associated with either an increase or no change in hospital-wide mortality rates of inpatients. Despite widespread enthusiasm for CPOE as a tool to help transform quality and patient safety, no published studies to date have associated CPOE implementation with significant reductions in hospital-wide mortality rates. OBJECTIVE: The objective of this study was to determine the effect on the hospital-wide mortality rate after implementation of CPOE at an academic children's hospital. PATIENTS AND METHODS: We performed a cohort study with historical controls at a 303-bed, freestanding, quaternary care academic children's hospital. All nonobstetric inpatients admitted between January 1, 2001, and April 30, 2009, were included. A total of 80 063 patient discharges were evaluated before the intervention (before November 1, 2007), and 17 432 patient discharges were evaluated after the intervention (on or after November 1, 2007). On November 4, 2007, the hospital implemented locally modified functionality within a commercially sold electronic medical record to support CPOE and electronic nursing documentation. RESULTS: After CPOE implementation, the mean monthly adjusted mortality rate decreased by 20% (1.008–0.716 deaths per 100 discharges per month unadjusted [95% confidence interval: 0.8%–40%]; P = .03). With observed versus expected mortality-rate estimates, these data suggest that our CPOE implementation could have resulted in 36 fewer deaths over the 18-month postimplementation time frame. CONCLUSION: Implementation of a locally modified, commercially sold CPOE system was associated with a statistically significant reduction in the hospital-wide mortality rate at a quaternary care academic children's hospital.

SUMMARY: HPE is a congenital brain malformation characterized by failure of the prosencephalon to divide into 2 hemispheres. We have identified 7 patients who have a mild subtype of HPE in which the midline fusion was restricted to the septal region or preoptic region of the telencephalon. This subtype, which we call septopreoptic HPE, falls in the spectrum of lobar HPE, but lacks significant frontal neocortical fusion seen in lobar HPE. Other imaging characteristics include thickened or dysplastic fornix, absent or hypoplastic anterior CC, and single unpaired ACA. The SP was fully formed in 4, partially formed in 2, and absent in 1. Mild midline craniofacial malformation, such as SMMCI and CNPAS were found in 86% and 71%, respectively. Patients outside of infancy often manifested language delay, learning disabilities, or behavioral disturbances, while motor function was relatively spared.

Holoprosencephaly (HPE) is a complex congenital brain malformation characterized by failure of the forebrain to bifurcate into two hemispheres, a process normally completed by the fifth week of gestation. Modern high‐resolution brain magnetic resonance imaging (MRI) has allowed detailed analysis of the cortical, white matter, and deep gray structural anomalies in HPE in living humans. This has led to better classification of types of HPE, identification of newer subtypes, and understanding of the pathogenesis. Currently, there are four generally accepted subtypes of HPE: alobar, semilobar, lobar, and middle interhemispheric variant. These subtypes are defined primarily by the degree and region of neocortical nonseparation. Rather than there being four discrete subtypes of HPE, we believe that there is a continuum of midline neocortical nonseparation resulting in a spectrum disorder. Many patients with HPE fall within the border zone between the neighboring subtypes. In addition, there are patients with very mild HPE, where the nonseparation is restricted to the preoptic (suprachiasmic) area. In addition to the neocortex, other midline structures such as the thalami, hypothalamic nuclei, and basal ganglia are often nonseparated in HPE. The cortical and subcortical involvements in HPE are thought to occur due to a disruption in the ventral patterning process during development. The severity of the abnormalities in these structures determines the severity of the neurodevelopmental outcome and associated sequelae. © 2010 Wiley‐Liss, Inc.

Holoprosencephaly (HPE) is the most common malformation of the human forebrain, and may be due to cytogenetic anomalies, teratogens, occur in the context of a syndrome, or be due to mutations in single genes associated with non-syndromic HPE. Mutations in ZIC2, a transcription factor located on chromosome 13q32, are the secondmost common cause of non-syndromic, non-chromosomal HPE. Blood samples from over 1000 individuals with HPE-spectrum disorders and their relatives were analyzed for sequence variations in ZIC2. We examined clinical details and included all other known previously published and unpublished cases of mutations in ZIC2 through a literature search and collaboration with other centers. We find mutations in ZIC2 in 8% of probands with HPE, and describe 153 individuals from 116 unrelated kindreds, including 137 patients with molecularly-determined mutations in ZIC2 and 16 patients with deletions of the ZIC2 locus. Unlike HPE due to mutations in other genes, the vast majority of cases are sporadic and the proportional distribution of HPE types differs significantly from previously published analyses of non-chromosomal non-syndromic HPE. Furthermore, we describe a novel facial phenotype in patients with mutations in ZIC2 which includes bitemporal narrowing, upsplanting palpebral fissures, a short nose with anteverted nares, and a broad and well-demarcated philtrum, and large ears. This phenotype is distinct from the standard facial dysmorphisms associated with nonchromosomal, non-syndromic HPE. Our findings show that HPE due to mutations in ZIC2 is distinct from that due to mutations in other genes. This may shed light on the mechanisms that contribute to the formation of the face and the forebrain and may help direct genetic counseling and diagnostic strategies.

This chapter focuses on some of the more common brain malformations that are encountered early in life. Tremendous advances in neuroimaging with MRI in the past two decades have significantly improved our ability to diagnose brain malformations. In conjunction, there have been rapid advances in neurobiology that have led to better understanding of how the brain develops and what disturbances to the development lead to malformation. Each year more and more genes responsible for malformations are being discovered. Furthermore, modern fetal ultrasonography and more recently fetal MRI have increased the ability to detect a large variety of central nervous system malformations in utero. Prenatal detection and anatomic diagnosis of the malformations will better allow the medical caregivers to provide prognosis and management counseling.

We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6 . PAX6 is a transcription factor involved in eye and brain development and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals. Published 2009 Wiley‐Liss, Inc.