Evidentiary Significance of Routine EEG in Refractory Cases: A Paradigm Shift in Psychiatry.

Over the past decade, the Diagnostic and Statistical Manual's method of prescribing medications based on presenting symptoms has been challenged. The shift toward precision medicine began with the National Institute of Mental Health and culminated with the World Psychiatric Association's posit that a paradigm shift is needed. This study supports that shift by providing evidence explaining the high rate of psychiatric medication failure and suggests a possible first step toward precision medicine. A large psychiatric practice began collecting electroencephalograms (EEGs) for this study in 2012. The EEGs were analyzed by the same neurophysiologist (board certified in electroencephalography) on 1,233 patients. This study identified 4 EEG biomarkers accounting for medication failure in refractory patients: focal slowing, spindling excessive beta, encephalopathy, and isolated epileptiform discharges. Each EEG biomarker suggests underlying brain dysregulation, which may explain why prior medication attempts have failed. The EEG biomarkers cannot be identified based on current psychiatric assessment methods, and depending upon the localization, intensity, and duration, can all present as complex behavioral or psychiatric issues. The study highlights that the EEG biomarker identification approach can be a positive step toward personalized medicine in psychiatry, furthering the clinical thinking of "testing the organ we are trying to treat."

Isolated epileptiform activity in children and adolescents: prevalence, relevance, and implications for treatment.

In the field of psychiatry diagnoses are primarily based on the report of symptoms from either the patient, parents, or both, and a psychiatrist's observations. A psychiatric diagnosis is currently the most widely used basis for medication selection and the brain is seldom investigated directly as a source of those symptoms. This study addresses the request from the National Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC) for scientific research into neurological abnormalities that can be linked to psychiatric symptoms for the purpose of predicting medication response. One such neurological abnormality that has been the focus of many studies over the last three decades is isolated epileptiform discharges (IEDs) in children and adolescents without seizures. We conducted a systematic review of the literature to determine prevalence rates of IEDs within diagnostic categories. We then compared the prevalence of IEDs in the selected literature to our IRB-approved data archive. Our study found a consistent high prevalence of IEDs specifically for ADHD (majority > 25%) and ASD (majority > 59%), and consistent low prevalence rates were found for Depression (3%). If children and adolescents have failed multiple medication attempts, and more than one-third of them have IEDs, then an EEG would be justified within the RDoC paradigm.

Treating Severe Traumatic Brain Injury: Combining Neurofeedback and Hyperbaric Oxygen Therapy in a Single Case Study.

In 2014, a 26-year-old male was involved in a motor vehicle accident resulting in a severe traumatic brain injury (TBI). The patient sustained a closed-head left temporal injury with coup contrecoup impact to the frontal region. The patient underwent a left side craniotomy and was comatose for 26 days. After gaining consciousness, he was discharged to a brain injury treatment center that worked with physical, speech, and occupational issues. He was discharged after eight months with significant speech, ambulation, spasticity, and cognitive issues as well as the onset of posttraumatic epilepsy. His parents sought hyperbaric oxygen treatment (HBOT) from a doctor in Louisiana. After 165 dives, the HBOT doctor recommended an addition of neurofeedback (NFB) therapy. In March 2019 the patient started NFB therapy intermixed with HBOT. The combination of NFB and HBOT improved plasticity and functionality in the areas of injury and the correlated symptoms including short-term memory, personality, language, and executive function, as well as significantly reducing the incidence of seizures. Severe brain injuries often leave lasting deficits with little hope for major recovery and there is a need for further research into long-term, effective neurological treatments for severe brain injuries. These results suggest that HBOT combined with NFB may be a viable option in treating severe brain injuries and should be investigated.

Clinical Application of Combined EEG-qEEG Functional Neuroimaging in the Practice of Pediatric Neuroscience: A Personal Perspective.

This brief article is an overview of my personal experience over the past almost 10 years of the clinical use of EEG and quantitative EEG (qEEG) functional neuroimaging in a busy pediatric neurology practice. The concomitant use of surface EEG and functional electromagnetic EEG neuroimaging/qEEG in clinical practice provides significant additional clinical and neurophysiologic information. The qEEG is a noninvasive, inexpensive, portable technique with high temporal resolution (milliseconds) and improving spatial resolution (down to 3 mm3) and is an appropriate and validated tool for investigation of abnormal brain dynamics and connectivity of neuronal networks in clinical disorders of the brain. This article describes the daily applicability and utility of this modality in assisting diagnosis and clinical management of patients with a wide variety of presenting symptoms, including headaches, tics, autism spectrum disorder, inattention, sleep dysregulation, anxiety, and depression. The ease of data acquisition and analysis in clinical practices, coupled with skilled interpretation and clinical application, makes this tool one of the most valuable clinical tools to complement a thorough history and examination process.

Effect of a Faith-Based Education Program on Self-Assessed Physical, Mental and Spiritual (Religious) Health Parameters.

The aim of the study was to determine the effect of attending a faith-based education program (FBEP) on self-assessed physical, mental and spiritual health parameters. The study was designed as a prospective, observational, cohort study of individuals attending a 5-day FBEP. Out of 2650 sequential online registrants, those previously unexposed to the FBEP received automated invitations to complete 5 sequential Self-Assessment Questionnaire's (SAQ's) containing: (1) Duke University Religion Index (DUREL); (2) Negative Religious Coping (N-RCOPE); (3) Perceived Stress Scale (PSS); (4) Center for Epidemiology and Statistics-Depression Scale (CES-D); (5) Brief Illness Perception Questionnaire (BIPQ); and the (6) State Trait Anxiety Inventory (STAI). Pre-attendance SAQ (S1) was repeated immediately post-FBEP (S2), at 30 days (S3), 90 days (S4) and after 1 year (S5). Of 655 invited, 274 (42 %) succeeded, 242 (37 %) failed and 139 (21 %) declined to complete S1. Of the 274, 37 (14 %) were excluded at on-site interview; 26 (9 %) never attended the FBEP (i.e., controls: 5♂; 21♀; 27-76 years); and 211 (77 %) participated (i.e., cases: 105♂; 106♀; 18-84 years) and were analyzed over time: 211 (S1); 192 (S2); 99 (S3); 52 (S4); 51 (S5). IRB approval was via the Human Research Ethics Committee of Stellenbosch University. DUREL showed significant, sustained changes in Intrinsic Religiosity. N-RCOPE showed significant, lasting improvement. In others, median values dropped significantly immediately after the FBEP (S1:S2) for STAI-State p < 0.0001; PSS p < 0.0001; BIPQ p < 0.0001; and CES-D p < 0.0001; and at 1 month (S1:S3) for STAI-Trait p < 0.001; all changes were sustained (S3 through S5). This FBEP produced statistically and clinically significant changes; these lasted in those followed up >1 year.

Integration of EEG Into Psychiatric Practice: A Step Toward Precision Medicine for Autism Spectrum Disorder.

INTRODUCTION: Data from an EEG is not commonly used by psychiatrists to plan treatment and medication. However, EEG abnormalities such as isolated epileptiform discharges are found to be more prevalent in psychiatric patients, particularly those diagnosed with autism spectrum disorder (ASD). Most medications prescribed for ASD lower seizure threshold and increase side effects. Therefore, it may be prudent to order an EEG for ASD cases, especially those categorized as refractory. METHODS: The data set was obtained from a multidisciplinary practice that treats a wide variety of neuroatypical children and adolescent refractory patients. This study investigated 140 nonepileptic subjects diagnosed with ASD, aged 4 to 25 years. Visual inspection of the EEG was performed to search for paroxysmal, focal, or lateralizing patterns. RESULTS: Of the 140 subjects, the EEG data identified 36% with isolated epileptiform discharges. The χ analysis found no significant difference between genders among the three age groups. Findings indicated a high prevalence of isolated epileptiform discharges among individuals with ASD. CONCLUSIONS: Our results find that compared with the healthy population, a large number of patients with ASD have isolated epileptiform discharges despite never having a seizure. Our findings support the use of EEG in children, adolescents, and young adults with ASD, regardless of gender or age. This is particularly true for those who exhibit aggressive behaviors or those who have failed previous medication attempts with stimulants, antidepressants, and/or antipsychotics.

Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis.

OBJECTIVE: To evaluate the clinical safety of antenatal and postnatal N-acetylcysteine (NAC) as a neuroprotective agent in maternal chorioamnionitis in a randomized, controlled, double-blinded trial. STUDY DESIGN: Twenty-two mothers >24 weeks gestation presenting within 4 hours of diagnosis of clinical chorioamnionitis were randomized with their 24 infants to NAC or saline treatment. Antenatal NAC (100 mg/kg/dose) or saline was given intravenously every 6 hours until delivery. Postnatally, NAC (12.5-25 mg/kg/dose, n = 12) or saline (n = 12) was given every 12 hours for 5 doses. Doppler studies of fetal umbilical and fetal and infant cerebral blood flow, cranial ultrasounds, echocardiograms, cerebral oxygenation, electroencephalograms, and serum cytokines were evaluated before and after treatment, and 12, 24, and 48 hours after birth. Magnetic resonance spectroscopy and diffusion imaging were performed at term age equivalent. Development was followed for cerebral palsy or autism to 4 years of age. RESULTS: Cardiovascular measures, cerebral blood flow velocity and vascular resistance, and cerebral oxygenation did not differ between treatment groups. Cerebrovascular coupling was disrupted in infants with chorioamnionitis treated with saline but preserved in infants treated with NAC, suggesting improved vascular regulation in the presence of neuroinflammation. Infants treated with NAC had higher serum anti-inflammatory interleukin-1 receptor antagonist and lower proinflammatory vascular endothelial growth factor over time vs controls. No adverse events related to NAC administration were noted. CONCLUSIONS: In this cohort of newborns exposed to chorioamnionitis, antenatal and postnatal NAC was safe, preserved cerebrovascular regulation, and increased an anti-inflammatory neuroprotective protein. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00724594.

Standardized database development for EEG epileptiform transient detection: EEGnet scoring system and machine learning analysis.

The routine scalp electroencephalogram (rsEEG) is the most common clinical neurophysiology procedure. The most important role of rsEEG is to detect evidence of epilepsy, in the form of epileptiform transients (ETs), also known as spike or sharp wave discharges. Due to the wide variety of morphologies of ETs and their similarity to artifacts and waves that are part of the normal background activity, the task of ET detection is difficult and mistakes are frequently made. The development of reliable computerized detection of ETs in the EEG could assist physicians in interpreting rsEEGs. We report progress in developing a standardized database for testing and training ET detection algorithms. We describe a new version of our EEGnet software system for collecting expert opinion on EEG datasets, a completely web-browser based system. We report results of EEG scoring from a group of 11 board-certified academic clinical neurophysiologists who annotated 30-s excepts from rsEEG recordings from 100 different patients. The scorers had moderate inter-scorer reliability and low to moderate intra-scorer reliability. In order to measure the optimal size of this standardized rsEEG database, we used machine learning models to classify paroxysmal EEG activity in our database into ET and non-ET classes. Based on our results, it appears that our database will need to be larger than its current size. Also, our non-parametric classifier, an artificial neural network, performed better than our parametric Bayesian classifier. Of our feature sets, the wavelet feature set proved most useful for classification.

Reduction of seizure occurrence from exposure to auditory stimulation in individuals with neurological handicaps: a randomized controlled trial.

BACKGROUND: The purpose of this work was to determine in a clinical trial the efficacy of reducing or preventing seizures in patients with neurological handicaps through sustained cortical activation evoked by passive exposure to a specific auditory stimulus (particular music). The specific type of stimulation had been determined in previous studies to evoke anti-epileptiform/anti-seizure brain activity. METHODS: The study was conducted at the Thad E. Saleeby Center in Harstville, South Carolina, which is a permanent residence for individuals with heterogeneous neurological impairments, many with epilepsy. We investigated the ability to reduce or prevent seizures in subjects through cortical stimulation from sustained passive nightly exposure to a specific auditory stimulus (music) in a three-year randomized controlled study. In year 1, baseline seizure rates were established. In year 2, subjects were randomly assigned to treatment and control groups. Treatment group subjects were exposed during sleeping hours to specific music at regular intervals. Control subjects received no music exposure and were maintained on regular anti-seizure medication. In year 3, music treatment was terminated and seizure rates followed. We found a significant treatment effect (p = 0.024) during the treatment phase persisting through the follow-up phase (p = 0.002). Subjects exposed to treatment exhibited a significant 24% decrease in seizures during the treatment phase, and a 33% decrease persisting through the follow-up phase. Twenty-four percent of treatment subjects exhibited a complete absence of seizures during treatment. CONCLUSION/SIGNIFICANCE: Exposure to specific auditory stimuli (i.e. music) can significantly reduce seizures in subjects with a range of epilepsy and seizure types, in some cases achieving a complete cessation of seizures. These results are consistent with previous work showing reductions in epileptiform activity from particular music exposure and offers potential for achieving a non-invasive, non-pharmacologic treatment of epilepsy. TRIAL REGISTRATION: Clinicaltrials.gov NCT01459692.

Web-based collection of expert opinion on routine scalp EEG: software development and interrater reliability.

Computerized detection of epileptiform transients (ETs), characterized by interictal spikes and sharp waves in the EEG, has been a research goal for the last 40 years. A reliable method for detecting ETs would assist physicians in interpretation and improve efficiency in reviewing long-term EEG recordings. Computer algorithms developed thus far for detecting ETs are not as reliable as human experts, primarily due to the large number of false-positive detections. Comparing the performance of different algorithms is difficult because each study uses individual EEG test datasets. In this article, we present EEGnet, a distributed web-based platform for the acquisition and analysis of large-scale training datasets for comparison of different EEG ET detection algorithms. This software allows EEG scorers to log in through the web, mark EEG segments of interest, and categorize segments of interest using a conventional clinical EEG user interface. This software platform was used by seven board-certified academic epileptologists to score 40 short 30-second EEG segments from 40 patients, half containing ETs and half containing artifacts and normal variants. The software performance was adequate. Interrater reliability for marking the location of paroxysmal activity was low. Interrater reliability of marking artifacts and ETs was high and moderate, respectively.

Sudden appearance of new upper extremity motor function while performing neurophysiologic intraoperative monitoring during tethered cord release: a case report.

UNLABELLED: : Tethered cord syndrome occurs when the distal spinal cord or filum adheres to adjacent structures resulting in progressive sensorimotor deficits in the lower extremities, fecal and/or urinary incontinence, and musculoskeletal deformities. Tethering of the distal cord may be idiopathic, may be associated with an intraspinal abnormality such as a lipoma, but most commonly the distal spinal cord remnant is adherent to the area of the original dysraphism repair in patients with myelodysplasia. Surgery to untether the cord is indicated in patients with worsening pain symptoms, progressive limb deformity or spasticity, or before any acute correction of an associated spinal deformity. Neurophysiologic intraoperative monitoring is used to minimize the risk of inadvertent nerve root or spinal cord injury during the untethering procedure and to assess any changes in cord function at the time of an associated spinal deformity correction. We present a patient with a lumbar level myelodysplasia, Chiari II malformation, severe scoliosis, and tethered cord that underwent concurrent scoliosis correction and tethered cord syndrome surgery, who demonstrated immediate intraoperative improvement in neurophysiologic responses in a previously flaccid upper extremity after untethering. These monitoring changes correlated with clinical improvements noted by physicians and family postoperatively. LEVEL OF EVIDENCE: Level IV.

Neurophysiologic intraoperative monitoring during selective dorsal rhizotomy.

Selective dorsal rootlet rhizotomy (SDR) is a neurosurgical procedure designed to reduce spasticity in the legs, although preserving motor and sensory function, of appropriately selected children with spastic quadraparesis. This is accomplished by neurophysiologicially guided (e.g., selective) severing of specific dorsal rootlets in the cauda equina. This decreases facilitatory input to spinal anterior motor neurons, thereby reducing spasticity in the legs. This first portion of this article discusses the neurophysiologic intraoperative monitoring techniques during SDR, with the understanding that there are no universally agreed upon protocols nor standards of care. The second portion of the article reviews supporting data for the utility of SDR and long-term outcomes. With major benefits attributed to the selective nature of the procedure, SDR was increasingly used in the 1980-1990's after its introduction by Fasano et al. (Neurochirurgie. 1976;22:23-34; Acta Neurochir. 1977;suppl 24:53-57; Child's Brain. 1978;4:289-305) and revision by Peacock and colleagues (S Afr Med J. 1981;60:849-850;S Afr Med J. 1982;62:119-124). More extensive SDR discussions of its history, theoretical and physiological bases, patient selection criteria, neurosurgical techniques, and postoperative and long-term management, may be found elsewhere.

Acute disseminated encephalomyelitis following infectious mononucleosis.

Two months following an Epstein-Barr virus infection, a 17-year-old white female presented with seizures, intermittent visual changes, and altered mental status. Magnetic resonance imaging showed white matter changes of acute disseminated encephalomyelitis with a predilection for posterior cerebral artery distributions but without radiological evidence of arteritis. Epstein-Barr virus titers and polymerase chain reaction analysis results for the virus were consistent with postinfectious acute disseminated encephalomyelitis. The symptoms and signs improved following treatment with high-dose corticosteroids and intravenous immunoglobulin. Although Epstein-Barr virus can cause acute viral encephalomyelitis, the authors report a case of acute disseminated encephalomyelitis months after acute Epstein-Barr virus infection.

Childhood paroxysmal kinesigenic dyskinesia: report of seven cases with onset at an early age.

We report on seven children who developed abnormal involuntary movements as early as 1.5 years after unremarkable term births. The paroxysmal episodes of abnormal movements were typically precipitated by sudden, voluntary movements, or a startle. The clinical features in each case were consistent with the diagnosis of paroxysmal kinesigenic dyskinesia (PKD). The episodes of abnormal movements are described. EEG was obtained in all cases, and video/electroencephalography (VEEG) monitoring was performed to exclude the possibility of epilepsy in six patients. VEEG studies revealed multiple events consistent with PKD; no ictal epileptiform discharges were recorded. The apparent benign nature of the disorder, as well as treatment options with antiepileptic drugs, was discussed with the parents, and most chose no pharmacologic treatment. We discuss clinical characteristics of PKD, treatment with anticonvulsant therapy, and recent insights into its possible pathophysiology.

Pediatric tick paralysis: discussion of two cases and literature review.

This report describes two cases of tick paralysis in children diagnosed within a 3-month period (May-July 2002) in rural South Carolina. Differing presenting symptoms consisted of acute onset of ataxia in one patient and acute ascending paralysis in the other. Ticks were present on the scalp of both patients and were removed immediately. Both girls demonstrated improvement of signs and symptoms within hours and complete recovery within 24 hours of tick removal. The diagnosis of tick paralysis must be considered in any patient, particularly children, who present with either acute ataxia or acute ascending paralysis. As in any clinical encounter, careful history and thorough general and neurologic examinations must be performed to exclude the possibility of tick attachment.

The acute effect of music on interictal epileptiform discharges.

This study was a prospective, randomized, single-blinded, crossover, placebo-controlled, pilot clinical trial investigating the effect of Mozart's Sonata for Two Pianos (K448) on the frequency of interictal epileptiform discharges (IEDs) from the EEGs of children with benign childhood epilepsy with centrotemporal spikes, or "rolandic" epilepsy. The goal was to demonstrate decreased frequency of IEDs with exposure to K448. Four subjects were recruited and 4-hour awake EEG recordings performed. IED frequency per minute was averaged over each of three epochs per hour. Mean IED count per epoch, standard deviations, and variance were calculated. Only complete waking epochs were analyzed. Two subjects demonstrated sufficient waking IEDs for statistical analysis, consisting of three epochs of K448-related effects. Significant decreases in IEDs per minute (33.7, 50.6, and 33.9%) were demonstrated comparing baseline with exposure to K448, but not to control music (Beethoven's Für Elise).