Faculty Bibliography

BACKGROUND:Children with familial dysautonomia (FD) are smaller and grow more slowly than the general population. It is unknown whether this abnormal growth is due to comorbidities that patients with FD live with, or if it is a direct effect of the disease-causing homozygous ELP-1 mutations. Here, we created growth curves for weight, height, and body mass index (BMI) in male and female children with FD to monitor the nutritional status of patients with FD. METHODS:We used the New York University (NYU) FD Registry which includes data from 680 individuals with FD who were followed longitudinally since birth. We generated sex-specific FD growth charts for three age ranges (birth to 36 months, 2 to 20 years, and 2 to 40 years) and compared them to the general population. We generated Kaplan-Meier curves to test the hypothesis that FD patients with low BMI had shorter survival than the rest of the cohort. RESULTS:Growth charts generated from 591 individuals with FD show that these patients grow more slowly, reach less height, and gain less weight than the general population. The impact of FD on height was more pronounced in girls than in boys. However, both groups showed markedly low weights, which resulted in low BMI. Low weight, but not height, is already evident at birth. In a subpopulation of FD patients, we found that treatment with growth hormone or spinal fusion surgery helped patients achieve the expected growth characteristic of FD patients, but these treatments did not lead FD patients to achieve the growth pattern of the general population. Contrary to our hypothesis, low BMI had no impact on patient survival. CONCLUSIONS:Pediatric patients with FD have lower height, weight, and BMI compared to the general pediatric population, but this does not appear to affect survival. Growth curves specific to the FD population are an important tool to monitor growth and nutritional status in pediatric patients with FD when the general population growth curves are of limited use.

BACKGROUND/UNASSIGNED:Anterior transthoracic, posterolateral (i.e., costotransversectomy/lateral extracavitary), and transpedicular approaches are now utilized to address anterior, anterolateral, or lateral thoracic disk herniations (TDH). Notably, laminectomy has not been a viable option for treating TDH for decades due to the much lower rate of acceptable outcomes (i.e., 57% for decompressive laminectomy vs. over 80% for the posterolateral, lateral, and transthoracic procedures), and a higher risk of neurological morbidity/paralysis. METHODS/UNASSIGNED:Patients with TDH averaged 48-56.3 years of age, and presented with pain (76%), myelopathy (61%-99%), radiculopathy (30%-33%), and/or sphincter loss (16.7%-24%). Those with anterior/anterolateral TDH (30-74%) were usually myelopathic while those with more lateral disease (50-70%) exhibited radiculopathy. Magnetic resonance (MR) studies best defined soft-tissue/disk/cord pathology, CAT scan (CT)/Myelo-CT studies identified attendant discal calcification (i.e. fully calcified 38.9% -65% vs. partial calcification 27.8%), while both exams documented giant TDH filling > 30 to 40% of the canal (i.e., in 43% to 77% of cases). RESULTS/UNASSIGNED:Surgical options for anterior/anterolateral TDH largely included transthoracic or posterolateral approaches (i.e. costotransversectomy, lateral extracavitary procedures) with the occasional use of transfacet/transpedicular procedures mostly applied to lateral disks. Notably, patients undergoing transthoracic, lateral extracavitary/costotransversectomy/ transpedicular approaches may additionally warrant fusions. Good/excellent outcomes were quoted in from 45.5% to 87% of different series, with early postoperative adverse events reported in from 14 to 14.6% of patients. CONCLUSION/UNASSIGNED:Anterior/anterolateral TDH are largely addressed with transthoracic or posterolateral procedures (i.e. costotransversectomy/extracavitary), with a subset also utilizing transfacet/transpedicular approaches typically adopted for lateral TDH. Laminectomy is essentially no longer considered a viable option for treating TDH.

Visual hallucinations are prevalent, potentially disabling symptoms of Parkinson's Disease. Multiple impairments in bottom-up sensory processing and top-down perceptual modulation are implicated in the pathophysiology of these phenomena. In healthy individuals, visual illusions are elicited by illusory figures through parametric manipulations of geometrical configurations, contrast, color, or spatial relationships between stimuli. These illusory percepts provide insight on the physiologic processes subserving conscious and unconscious perception. In this exploratory, cross-sectional, controlled study, perceptual performance on illusory figures was assessed on 11 PD patients with hallucinations, 10 non-hallucinating PD patients, and 10 age-matched healthy individuals. In order to characterize potential neural substrates of perceptual performances, patients' brain metabolic patterns on FDG PET were also analyzed. Illusions relying on attentional modulation and global perception were attenuated in PD patients without hallucinations. This pattern was no longer recognizable in hallucinating patients. Conversely, illusory effects normally counteracted by figure to background segregation and overlapping figures recognition were enhanced in PD patients with hallucinations. FDG PET findings further suggest that perceptual differences between PD patients might be linked to abnormal top-down perceptual modulation.

Neurologists in both the inpatient and outpatient settings are increasingly using ultrasound to diagnose and manage common neurological diseases. Advantages include cost-effectiveness, the lack of exposure to ionizing radiation, and the ability to perform at the bedside to provide real-time data. There is a growing body of literature that supports using ultrasonography to improve diagnostic accuracy and aid in performing procedures. Despite the increasing utilization of this imaging modality in medicine, there has been no comprehensive review of the clinical applications of ultrasound in the field of neurology. We discuss the current uses and limitations of ultrasound for various neurological conditions. We review the role for ultrasound in commonly performed neurologic procedures including lumbar puncture, botulinum toxin injections, nerve blocks, and trigger point injections. We specifically discuss the technique for ultrasound-assisted lumbar puncture and occipital nerve block as these are commonly performed. We then focus on the utility of ultrasound in the diagnosis of neurologic conditions. This includes neuromuscular diseases such as motor neuron disorders, focal neuropathies, and muscular dystrophy as well as vascular conditions such as stroke and vasospasm in subarachnoid hemorrhage. We also address ultrasound's use in critically ill patients to aid in identifying increased intracranial pressure, hemodynamics, and arterial and/or venous catheterization. Finally, we address the importance of standardized ultrasound curricula in trainee education and make recommendations for the future directions of research and competency guidelines within our specialty.

The utility of symptom (SVT) and performance (PVT) validity tests has been independently established in neuropsychological evaluations, yet research on the relationship between these two types of validity indices is limited to circumscribed populations and measures. This study examined the relationship between SVTs on the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and PVTs in a mixed neuropsychiatric setting. This cross-sectional study included data from 181 diagnostically and demographically diverse patients with neuropsychiatric conditions referred for outpatient clinical neuropsychological evaluation at an academic medical center. All patients were administered a uniform neuropsychological battery, including the MMPI-2-RF and five PVTs (i.e., Dot Counting Test; Medical Symptom Validity Test; Reliable Digit Span; Test of Memory Malingering-Trial 1; Word Choice Test). Nonsignificant associations emerged between SVT and PVT performance. Although the Response Bias Scale was most predictive of PVT performance, MMPI-2-RF SVTs generally had low classification accuracy for predicting PVT performance. Neuropsychological test performance was related to MMPI-2-RF SVT status only when overreporting elevations were at extreme scores. The current study further supports that SVTs and PVTs measure unique and dissociable constructs among diverse patients with neuropsychiatric conditions, consistent with literature from other clinical contexts. Therefore, objective evidence of symptom overreporting on MMPI-2-RF SVTs cannot be interpreted as definitively indicating invalid performance on tests of neurocognitive abilities. As such, clinicians should include both SVTs and PVTs as part of a comprehensive neuropsychological evaluation as they provide unique information regarding performance and symptom validity.

BACKGROUND:Headache disorders are among the most common and disabling medical conditions worldwide, have a great societal impact and are a common reason to seek medical care. Headache disorders are often misdiagnosed and undertreated, and the number of headache fellowship-trained physicians cannot meet patient demand. Educational initiatives for non-headache-specialist clinicians may be an avenue to increase clinician competency and patient access to appropriate management. OBJECTIVE:To undertake a scoping review of the educational initiatives in headache medicine for medical students, trainees, general practitioners/primary care physicians, and neurologists. METHODS:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews, an author (M.D.), with the help of a medical librarian, conducted a search of the Embase, Ovid Medline, and PsychInfo databases for articles related to medical educational initiatives on headache medicine in medical students, residents, and physicians over the last 20 years. RESULTS:A total of 17 articles met the inclusion criteria for this scoping review. Six articles were identified for medical students, seven for general practitioners/primary care physicians, one for emergency medicine residents, two for neurology residents, and one for neurologists. Certain educational initiatives were headache-focused while others had headaches as one of the educational topics. Educational content was delivered and assessed via diverse and innovative means, such as flipped classroom, simulation, theatrical performance, repeated quizzing and study, and a formalized headache elective. CONCLUSION/CONCLUSIONS:Education initiatives in headache medicine are important to improve competency and patient access to appropriate management of various headache disorders. Future research should focus on using innovative and evidence-based methods of content delivery, knowledge, and procedural assessment, and evaluating changes in practice behaviors.

After discharge from the Neurological Intensive Care Unit (NICU), patients often have new functional limitations and comorbidities requiring ongoing supportive care. In this review, we discuss the current state across the care continuum and identify opportunities for improvement.

BACKGROUND/UNASSIGNED:Patients with postoperative spinal epidural hematomas (pSEH) typically require emergency treatment to avoid paralysis; these hematomas should not be ignored. pSEH patients need to undergo immediate MR studies to document the location/extent of their hematomas, and emergent surgical decompression with/ without fusion if warranted. METHODS/UNASSIGNED:The frequencies of symptomatic pSEH ranged in various series from 0.1%-4.46%. Major predisposing factors included; perioperative/postoperative coagulation abnormalities/disorders, multilevel spine surgeries, previous spine surgery, and intraoperative cerebrospinal fluid (CSF) leaks. For surgery at all spinal levels, one study observed pSEH developed within an average of 2.7 postoperative hours. Another series found 100% of cervical/thoracic, and 50% of lumbar pSEH were symptomatic within 24 postoperative hrs., while a third series noted a 24-48 postoperative window for pSEH to develop. RESULTS/UNASSIGNED:Early recognition of postoperative symptoms/signs of pSEH, warrant immediate MR examinations to diagnose the local/extent of hemorrhages. Subsequent emergent spinal decompressions/fusions are critical to limit/avert permanent postoperative neurological deficits. Additionally, patients undergoing open or minimally invasive spinal procedures where pSEH are suspected, warrant immediate postoperative MR studies. CONCLUSION/UNASSIGNED:Patients undergoing spinal surgery at any level typically become symptomatic from pSEH within 2.7 to 24 postoperative hours. Early recognition of new neurological deficits, immediate MR studies, and emergent surgery (i.e., if indicated) should limit/minimize postoperative neurological sequelae. Thus, pSEH should be treated, not ignored.

BACKGROUND/UNASSIGNED:Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis. METHODS/UNASSIGNED:We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility. RESULTS/UNASSIGNED:Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases. CONCLUSIONS/UNASSIGNED:DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.

INTRODUCTION/UNASSIGNED:Alzheimer's disease (AD) and epilepsy are reciprocally related. Among sporadic AD patients, clinical seizures occur in 10-22% and subclinical epileptiform abnormalities occur in 22-54%. Cognitive deficits, especially short-term memory impairments, occur in most epilepsy patients. Common neurophysiological and molecular mechanisms occur in AD and epilepsy. The choroid plexus undergoes pathological changes in aging, AD, and epilepsy, including decreased CSF turnover, amyloid beta (Aβ), and tau accumulation due to impaired clearance and disrupted CSF amino acid homeostasis. This pathology may contribute to synaptic dysfunction in AD and epilepsy. METHODS/UNASSIGNED:= 12) using laser capture microdissection (LCM) followed by label-free quantitative mass spectrometry on the choroid plexus adjacent to the hippocampus at the lateral geniculate nucleus level. RESULTS/UNASSIGNED: DISCUSSION/UNASSIGNED:We found altered signaling pathways in the choroid plexus of severe AD cases and many correlated changes in the protein expression of cell metabolism pathways in AD and epilepsy cases. The shared molecular mechanisms should be investigated further to distinguish primary pathogenic changes from the secondary ones. These mechanisms could inform novel therapeutic strategies to prevent disease progression or restore normal function. A focus on dual-diagnosed AD/epilepsy cases, specific epilepsy syndromes, such as temporal lobe epilepsy, and changes across different severity levels in AD and epilepsy would add to our understanding.