Faculty Bibliography

OBJECTIVE:This study examined concordance between symptom and performance validity among clinically-referred patients undergoing neuropsychological evaluation for Attention-Deficit/Hyperactivity Disorder (ADHD). METHOD:Data from 203 patients who completed the WAIS-IV Working Memory Index, the Clinical Assessment of Attention Deficit-Adult (CAT-A), and ≥4 criterion performance validity tests (PVTs) were analyzed. RESULTS: CONCLUSION:Symptom and performance invalidity represent dissociable constructs in patients undergoing neuropsychological evaluation of ADHD and should be evaluated independently.

INTRODUCTION: Subarachnoid Hemorrhage (SAH) associated headaches are severe and challenging to manage. The use of sedating, high-dose opioids can cloud neurological assessments, leading to unnecessary testing and potentially increase the risk of dependence. We hypothesized that a tiered opioid sparing pain management protocol favoring NSAIDs and gabapentin for low grade SAH patients would decrease opioid use without adversely affecting headache severity scores.
METHOD(S): We performed a retrospective cohort study pre- and post-implementation of the opioid sparing protocol. Inclusion criteria included admission to NYU Langone-Brooklyn Hospital with Hunt Hess Grade 1 or 2 aneurysmal SAH on Day 3 of hospital admission as most patients received periprocedural sedation and analgesia during the first 2 days. The pre-implementation group (pre) was admitted from 8/2016 to 8/2017 and the post-implementation group (post) was admitted from 4/2019 to 4/2020. The two-year washout period was included because newly hired intensivists integrated elements of opioid-sparing protocols as part of their practice prior to the go-live date. We collected demographics, baseline admission characteristics, hospital complications, and past history of headaches and opioid use. From day 3-7, we tracked total use of morphine milligram equivalents (MME) of all opioids, acetaminophen, NSAIDS, barbiturates, and gabapentin. We recorded the highest (HP) and lowest (LP) visual analogue pain assessment scores in daily quartiles. Data analysis was completed with SPSS.
RESULT(S): 55 patients (n=24 pre and n=31 post) were eligible and enrolled in the study. 85 patients were excluded. Aneurysm location, surgical method, symptomatic vasospasm, and EVD placement were similar between groups. Hydrocephalus was more common in pre; EVD complications were more common in post. There were no documented stress ulcers nor re-hemorrhage attributed to medications. The protocol resulted in a 19% decrease in total average MME compared to baseline use ((21.7 vs 26.9, p=0.77), a 12% decrease in average HP (2.60 vs. 2.96, p=0.41), and a 30% decrease in average LP (0.63 vs. 0.90, p=0.16), although not statistically significant. 14 pre received barbiturates; 0 post.
CONCLUSION(S): Pain control with reduced opioid usage can be achieved with a tiered opioid sparing pain protocol

OBJECTIVE:The number, unpredictability, and severity of seizures experienced by patients with Dravet syndrome (DS) negatively impact quality of life (QOL) for patients, caregivers, and families. Metrics are needed to assess whether patients with residual seizures have moved meaningfully toward seizure freedom after treatment with new antiseizure medications. METHODS:We evaluated the time required postrandomization for each patient to experience the same number of seizures experienced during baseline (i.e., time-to-nth seizure), using a post hoc time-to-event (TTE) analysis of data from two Phase 3 placebo-controlled trials of adjunctive fenfluramine for DS (Study 1, N = 119; Study 2, N = 87). Patients aged 2-19 years were randomized to placebo or adjunctive fenfluramine (Study 1: .7 mg/kg/day or .2 mg/kg/day; Study 2: .4 mg/kg/day with stiripentol). Data were analyzed by Kaplan-Meier TTE curves and waterfall plots. RESULTS:The proportion of patients who never reached baseline seizure frequency was greater with fenfluramine than with placebo (Study 1: fenfluramine .7 mg/kg/day, 60%; fenfluramine .2 mg/kg/day, 31%; placebo, 13%; Study 2: fenfluramine .4 mg/kg/day, 58%; placebo, 2%). Median time-to-nth seizure was longer after fenfluramine than after placebo (Study 1: fenfluramine .7 mg/kg/day, 13 weeks; .2 mg/kg/day, 10 weeks; placebo, 7 weeks; Study 2: fenfluramine .4 mg/kg/day, 13 weeks; placebo, 5 weeks; p < .001). Longest duration of convulsive seizure-free days was increased in active groups versus the placebo group (Study 1: fenfluramine .7 and .2 mg/kg/day, 25.0 and 15.0 days; placebo, 9.5 days [p = .0001; p = .0352]; Study 2: fenfluramine .4 mg/kg/day, 22.0 days; placebo, 13.0 days [p = .004]). The most common adverse events included decreased appetite, pyrexia, upper respiratory tract infection, diarrhea, and fatigue. SIGNIFICANCE/CONCLUSIONS:These data demonstrate that fenfluramine can significantly reduce day-to-day seizure burden in patients with DS, providing prolonged periods of convulsive seizure-free days, which may help reduce the physical and emotional disease toll while improving health-related QOL for patients and caregivers.

Transcranial electrical stimulation (tES) comprises noninvasive neuromodulation techniques that deliver low-amplitude electrical currents to targeted brain regions with the goal of modifying neural activities. Expanding evidence from the past decade, specifically using transcranial direct current simulation and transcranial alternating current stimulation, presents promising applications of tES as a treatment for psychiatric disorders. In this review, the authors discuss the basic technical aspects and mechanisms of action of tES in the context of clinical research and practice and review available evidence for its clinical use, efficacy, and safety. They also review recent advancements in use of tES for the treatment of depressive disorders, schizophrenia, substance use disorders, and obsessive-compulsive disorder. Findings largely support growing evidence for the safety and efficacy of tES in the treatment of patients with resistance to existing treatment options, particularly demonstrating promising treatment outcomes for depressive disorders. Future directions of tES research for optimal application in clinical settings are discussed, including the growing home-based, patient-friendly methods and the potential pairing with existing pharmacological or psychotherapeutic treatments for enhanced outcomes. Finally, neuroimaging advancements may provide more specific mapping of brain networks, aiming at more precise tES therapeutic targeting in the treatment of psychiatric disorders.

Background/UNASSIGNED:wild-type glioblastoma. Methods/UNASSIGNED:wild-type newly diagnosed and recurrent glioblastoma patients who were treated with laser ablation at 14 US centers between January 2016 and May 2019. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable differences in survival, and median survival numbers. Results/UNASSIGNED:promoter methylation, adjuvant chemotherapy within 12 weeks, and tumor volume <3 cc. Conclusions/UNASSIGNED:wild-type newly diagnosed glioblastoma is comparable to outcomes observed in other tumor resection studies when those patients undergo radiation and chemotherapy following LITT.

BACKGROUND:The clinical diagnosis of multiple system atrophy (MSA) is challenged by overlapping features with Parkinson's disease (PD) and late-onset ataxias. Additional biomarkers are needed to confirm MSA and to advance the understanding of pathophysiology. Positron emission tomography (PET) imaging of the translocator protein (TSPO), expressed by glia cells, has shown elevations in MSA. OBJECTIVE:In this multicenter PET study, we assess the performance of TSPO imaging as a diagnostic marker for MSA. METHODS:C]PBR28 binding to TSPO using imaging data of 66 patients with MSA and 24 patients with PD. Group comparisons were based on regional analysis of parametric images. The diagnostic readout included visual reading of PET images against clinical diagnosis and machine learning analyses. Sensitivity, specificity, and receiver operating curves were used to discriminate MSA from PD and cerebellar from parkinsonian variant MSA. RESULTS:C]PBR28 binding to TSPO in MSA as compared with PD, with "hotspots" in the lentiform nucleus and cerebellar white matter. Visual reading discriminated MSA from PD with 100% specificity and 83% sensitivity. The machine learning approach improved sensitivity to 96%. We identified MSA subtype-specific TSPO binding patterns. CONCLUSIONS:We found a pattern of significantly increased regional glial TSPO binding in patients with MSA. Intriguingly, our data are in line with severe neuroinflammation in MSA. Glia imaging may have potential to support clinical MSA diagnosis and patient stratification in clinical trials on novel drug therapies for an α-synucleinopathy that remains strikingly incurable. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PURPOSE OF REVIEW/OBJECTIVE:Seizures, including status epilepticus, have been reported in association with acute COVID-19 infection. People with epilepsy (PWE) have suffered from seizure exacerbations during the pandemic. This article reviews the data for clinical and electrographic seizures associated with COVID-19, technical EEG considerations for reducing risk of transmission, and factors contributing to seizure exacerbations in PWE as well as strategies to address this issue. RECENT FINDINGS/RESULTS:An increasing number of studies of larger cohorts, accounting for a variety of variables and often utilizing EEG with standardized terminology, are assessing the prevalence of seizures in hospitalized patients with acute COVID-19 infections, and gaining insight into the prevalence of seizures and their effect on outcomes. Additionally, recent studies are evaluating the effect of the pandemic on PWE, barriers faced, and the usefulness of telehealth. Although there is still much to learn regarding COVID-19, current studies help in assessing the risk of seizures, guiding EEG utilization, and optimizing the use of telehealth during the pandemic.

Cardiac arrest can cause hypoxic-anoxic ischemic brain injury due to signaling cascades that lead to damaged cell membranes and vital cellular organelles, resulting in cell death in the setting of low or no oxygen. Some brain areas are more prone to damage than others, so patients with hypoxic-anoxic ischemic brain injury present with several outcomes, including reduced level of consciousness or alertness, memory deficits, uncoordinated movements, and seizures. Some patients may have mild deficits, while others may have such severe injury that it can progress to brain death. High-quality cardiopulmonary resuscitation is a proven technique to improve outcome after cardiac arrest, although morbidity and mortality remain high. Induced hypothermia, which involves artificially cooling the body immediately after cardiac arrest, may reduce injury to the brain and improve morbidity and mortality. Neuroprognostication after cardiac arrest is challenging and requires a multimodal approach involving clinical neurologic examinations, brain imaging, electrical studies to assess brain activity, and biomarkers to predict outcome.

OBJECTIVE:We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)-resistant vs ASM-responsive outcome for patients with idiopathic generalized epilepsy (IGE). METHODS:This was a case-control study of ASM-resistant cases and ASM-responsive controls with IGE treated at five epilepsy centers in the United States and Australia between 2002 and 2018. We recorded clinical characteristics and findings from the first available EEG study for each patient. We then compared characteristics of cases vs controls using multivariable logistic regression to develop a predictive model of ASM-resistant IGE. RESULTS:We identified 118 ASM-resistant cases and 114 ASM-responsive controls with IGE. First, we confirmed our recent finding that catamenial epilepsy is associated with ASM-resistant IGE (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.32-10.41, for all study subjects) after covariate adjustment. Other independent factors seen with ASM resistance include certain seizure-type combinations (absence, myoclonic, and generalized tonic-clonic seizures [OR 7.06, 95% CI 2.55-20.96]; absence and generalized tonic-clonic seizures [OR 4.45, 95% CI 1.84-11.34]), as well as EEG markers of increased generalized spike-wave discharges (GSWs) in sleep (OR 3.43, 95% CI 1.12-11.36 for frequent and OR 7.21, 95% CI 1.50-54.07 for abundant discharges in sleep) and the presence of generalized polyspike trains (GPTs; OR 5.49, 95% CI 1.27-38.69). The discriminative ability of our final multivariable model, as measured by area under the receiver-operating characteristic curve, was 0.80. SIGNIFICANCE:Multiple clinical and EEG characteristics independently predict ASM resistance in IGE. To improve understanding of a patient's prognosis, clinicians could consider asking about specific seizure-type combinations and track whether they experience catamenial epilepsy. Obtaining prolonged EEG studies to record the burden of GSWs in sleep and assessing for the presence of GPTs may provide additional predictive value.

Patients admitted to the hospital with neurological problems are sometimes incapacitated and unable to make end-of-life decisions. In these instances, without an advanced directive from the patient, clinicians and family members must make critical medical decisions without input from the patient. This paper looks at two cases - one child and one adult - in which neuroprognosis was uncertain, and physician and family members' beliefs on end-of-life care clash. We provide insight into these disagreements and reflect on how best to manage them. We argue that when considering withdrawing treatment, respecting autonomy is of paramount importance, while decision-making about continuing life-sustaining treatment requires clinicians to ensure surrogates are adequately educated about the principle of beneficence.