Search

The ictal–interictal continuum (IIC) is a concept used for those particular EEG patterns that do not meet the strict criteria for status epilepticus but may be associated with neuronal injury. The aim of this article is to review equivocal periodic patterns and to discuss their clinical significance along the IIC. The risk of seizures increases when the frequency of periodic discharges exceeds 2 Hz and when the pattern has features of superimposed rhythmic, sharp, or fast activity (plus modifier). Lateralized periodic discharges (LPDs) are one of the best examples of the IIC. Criteria have been proposed for identifying patterns along the IIC that we called “peri-ictal” LPDs. There is ongoing debate about when to treat patients with these EEG patterns along this spectrum. The term IIC is only an EEG description, and does not in itself reflect a clinical diagnosis, hence management is based on EEG alone. The decision to intensify treatment is based on the combination of EEG, the underlying etiology, the level of consciousness, comorbidities, imaging, and other surrogates of “damage.”

Electroencephalogram is used for prognostication and diagnosis in critically ill patients and is vital in developing clinical management algorithms. Unique waveforms on EEG may distinguish neurological disorders and define a potential for seizures. To better characterize zeta waves, we sought to define their electroclinical spectrum.We performed a systematic review using MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Review [through Ovid], Scopus, Science Citation Index Expanded and Emerging Sources Citation Index [through the Web of Science], and Epistemonikos. Grey literature resources were searched.Five hundred thirty-seven articles were identified. After excluding duplicates and reviewing titles, abstracts, and bodies and bibliographies of articles, four studies reported 64 cases describing data from patients with zeta waves, with a prevalence of 3 to 4%. Various and often incomplete clinical, neuroimaging, and EEG data were available. 57 patients (89.1%) had a focal cerebral lesion concordant with the location of zeta waves on EEG. 26 patients (40.6%) had clinical seizures, all but one being focal onset. Thirteen patients (20%) had epileptiform activity on EEG. Typically, zeta waves were located in the frontal head regions, often with generalized, frontal, predominant, rhythmic delta activity and associated with focal EEG suppression.Zeta waves frequently represent an underlying focal structural lesion. Their presence suggests a heightened risk for seizures. The small number of retrospective cases series in the literature reporting zeta waves might be an underrepresentation. We suggest a need for prospective studies of cEEG in critically ill patients to determine their clinical significance.

Prognostication following cardiorespiratory arrest relies on the neurological examination, which is supported by neuroimaging and neurophysiological testing. Acute posthypoxic myoclonus (PHM) is a clinical entity that has prognostic significance and historically has been considered an indicator of poor outcome, but this is not invariably the case. "Malignant" and more "benign" forms of acute PHM have been described and differentiating them is key in understanding their meaning in prognosis. Neurophysiological tests, electroencephalogram in particular, and clinical phenotyping are crucial in defining subtypes of acute PHM. This review describes the neurophysiological and phenotypic markers of malignant and benign forms of acute PHM, a clinical approach to evaluating acute PHM following cardiorespiratory arrest in determining prognosis, and gaps in our understanding of acute PHM that require further study.

BACKGROUND AND OBJECTIVES: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as “ictal-interictal-injury continuum” (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns. METHODS: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet, to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes. RESULTS: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and “other” classes, SPaRCNet exceeds the following percentages of 20 experts—ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively. DISCUSSION: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists.

Objective:To compare specific life stressors and domestic abuse that pregnant women with epilepsy (WWE) experience compared to pregnant women without epilepsy (WWoE).Methods:The Pregnancy Risk Assessment Monitoring System (PRAMS) is an annual weighted survey of randomly sampled postpartum women administered by the Centers for Disease Control (CDC). We used data from PRAMS from 2012-2020 in 13 states to assess the life stressors reported by WWE compared to WWoE. We adjusted the data for maternal age, race, ethnicity, marital status, education, and socioeconomic status (SES; using income, WIC, and Medicaid use). We also examined reported abuse in WWE compared to WWoE.Results:This study included data from 64,951 postpartum women, representing 4,072,189 women through weighted sampling. Of these, 1,140 reported having a diagnosis of epilepsy in the 3 months prior to their pregnancies (representing 81,021 WWE). WWE experienced a higher number of stressors compared to WWoE. WWE were more likely to have experienced 9 out of the 14 stressors asked in the PRAMS questionnaire: severe illness of a close family member, separation or divorce, homelessness, loss of a partner’s job, cut in work hours or pay, arguing more than usual with their partner, serving jail time, substance abuse problem in a close contact, and death of a close contact. After adjusting for demographics (age, race, and SES), epilepsy was still associated with a higher number of stressors in pregnant women. Other factors associated with stressors were younger age, Indigenous or mixed race, non-Hispanic ethnicity, lower income, and WIC or Medicaid use. Those who were married were less likely to report stressors. WWE were also more likely to report abuse before or during their pregnancies.Conclusions:While managing stress is important in both epilepsy and pregnancy, WWE experience more stressors than do WWoE. After adjusting for maternal age, race, and SES, this increase in stressors persisted. Women who were younger, with lower income, on WIC or Medicaid, or not married also were more likely to experience life stressors. Alarmingly, reported abuse was also higher in WWE compared to WWoE. Attention from clinicians and support services for WWE is needed to optimize good pregnancy outcomes.

Controlled incorporation of nitrogen into macromolecular skeletons is a long-standing challenge whose resolution would enable the preparation of soft materials with the scalability of man-made plastics and functionality of Nature’s proteins. Nylons and polyurethanes notwithstanding, nitrogen-rich polymer backbones remain scarce, and their synthesis typically lacks precision. Here we report a strategy that begins to address this limitation founded on a mechanistic discovery: ring-opening metathesis polymerization (ROMP) of carbodiimides followed by carbodiimide derivatization. An iridium guanidinate complex was found to initiate and catalyze ROMP of N-aryl and N-alkyl cyclic carbodiimides. Nucleophilic addition to the resulting polycarbodiimides enabled the preparation of polyureas, polythioureas, and polyguanidinates with varied architectures. This work advances the foundations of metathesis chemistry and opens the door to systematic investigations of structure-folding-property relationships in nitrogen-rich macromolecules.

Aims Seizures and status epilepticus (SE) are detected in almost a third of the comatose cardiac arrest survivors. As the literature is quite exhaustive regarding SE with motor symptoms in those patients, little is known about nonconvulsive SE (NCSE). Our aim was to compile the evidence from the literature of the frequency and outcome of NCSE in adult patients remaining in coma after resuscitation. Methods The medical search PubMed was screened for most relevant articles reporting the emergence and outcome of NCSE in comatose post-resuscitated adult patients. Results We identified 11 cohort studies (four prospective observational, seven retrospective) including 1092 patients with SE in 29–96% and NCSE reported in 1–20%. EEG evaluation started at a median of 9.5 h (range 7.5–14.8) after cardiac arrest, during sedation and targeted temperature management (TTM). Favorable outcome after NCSE occurred in 24.5%. We found no study reporting EEG to detect or exclude NCSE in patients remaining in coma prior to the initiation of TTM and without sedation withing the first hours after ROSC. Discussion Studies on NCSE after ROSC are scarce and unsystematic, reporting favorable outcome in every fourth patient experiencing NCSE after ROSC. This suggests that NCSE is often overlooked and outcome after NCSE is not always poor. The low data quality does not allow firm conclusions regarding the effects of NCSE on outcome calling for further investigation. In the meantime, clinicians should avoid equating NCSE after ROSC with poor prognosis.

Background and ObjectiveMedication management in pregnant women with epilepsy (PWWE) poses challenges, and understanding the effects of metabolic changes on antiseizure medications (ASMs) is important in planning care for PWWE. The possible teratogenic effects and risks of poorly controlled seizures have to be weighed. There are data in the literature on clinical management of ASMs including the effects of drug levels on seizures and factors that predict seizure frequency, but timing and frequency of monitoring and dose adjustment paradigms have not been well studied.MethodsThis retrospective study was approved by the Institutional Review Board at Johns Hopkins University. We retrospectively identified adult PWWE evaluated during pregnancy at the Johns Hopkins Bayview Medical Center epilepsy clinic, between January 1, 2007, and January 1, 2021. We reviewed charts for information regarding demographics, medical and epilepsy history, medications, serum drug levels, and dosing paradigms. We assessed risk factors for breakthrough seizures with a focus on frequency and timing of laboratory testing. We calculated the dose-normalized concentration (DNC) for analysis with levetiracetam and lamotrigine, assessing changes in DNC over time by half trimesters, and analyzed DNC and effects on seizures in pregnancy. We also compared preemptive vs clinically based lamotrigine dose adjustments in managing epilepsy in pregnancy.ResultsA total of 45 pregnancies in 39 patients were included in this study, 8 generalized, 28 focal epilepsy, and 3 unclassified. 31 PWWE (36 pregnancies) were on lamotrigine and/or levetiracetam, and 14 of these pregnancies experienced breakthrough seizures, 77% in the first trimester. Seizures led to the diagnosis of pregnancy in 5 patients. The DNC for levetiracetam decreased significantly compared with prepregnancy levels by the second half of the first trimester and demonstrated variable but frequently significant or near significant reduction throughout pregnancy. DNC for lamotrigine decreased significantly in the first half of the first trimester and remained significant throughout pregnancy. Age of mother at conception, week of first ASM serum level and number of levels obtained during pregnancy, and epilepsy type were not associated with breakthrough/increase in seizures. The history of drug resistance (p= 0.038) was associated with a higher odds of seizures. In those on lamotrigine, preemptive dose adjustments demonstrated similar results regarding seizure control when compared with clinical-based or laboratory-based dose management (p= 0.531).DiscussionThis study demonstrates that frequency and timing of ASM level monitoring may not affect overall seizure outcomes during pregnancy in those on lamotrigine or levetiracetam. Furthermore, one can consider preemptive dose adjustments or a laboratory-based/clinical-based approach in managing lamotrigine as both seem safe and feasible. However, in those with drug-resistant epilepsy before pregnancy, earlier and closer monitoring is warranted given the risk of seizures early during pregnancy. Larger prospective studies are needed to confirm these results.

SUMMARY The entity of triphasic waves (TWs) and TW encephalopathy has derived from the subjective art of EEG interpretation. Indeed, there are few if any guidelines regarding many different aspects of TWs. The authors seek to shed light on the nature and the diagnostic characteristics of various types of TWs, differentiating "typical" from "atypical" forms. The authors conclude that morphologies in the form of bursts of well-formed, smoothly contoured, negative-positive-negative, bilateral, symmetrical and synchronous, regular, reactive, periodic or rhythmic, 1.5 to 2.0 Hz, fronto-central, triphasic complexes with fronto-occipital lag meet the criteria for typical TWs and are highly suggestive of toxic-metabolic encephalopathies. These are most frequently hepatic, uremic, or sepsis-associated encephalopathies with multi-organ failure. In such cases, atypical TWs (frontopolar or parieto-occipital maximum, negative-positive or negative-positive-negative, asymmetric and asynchronous, unreactive, irregular, multifocal, continuous with spatiotemporal evolution, sharper and without fronto-occipital/occipito-frontal lag, or triphasic delta waves) are rarely seen. Atypical TWs are encountered in Angelman syndrome, toxic encephalopathies, hyperthyroidism/hypothyroidism, Hashimoto encephalopathy, nonconvulsive status epilepticus, dementia, sepsis-associated encephalopathy, cerebrovascular disorders, and certain boundary syndromes. Investigations describing TWs with uncommon etiologies revealed few with typical TWs, suggesting that the term "TWs" has been overused in the past. Triphasic waves arise from the interaction of multiple factors including toxic, metabolic, infectious, and structural disorders that affect circuits between thalamus and cortex. The patient's metabolic status, presence of potentially neurotoxic drugs, cerebral atrophy, white matter disease, dementia, or seizures help differentiate typical from typical TWs. Future studies will determine whether this dichotomy is heuristically and clinically helpful.

SUMMARY Triphasic waves are a fascinating and mysterious EEG feature. We now have to accept that, at times, epileptiform discharges may have a blunted "triphasic morphology," and that there may be great difficulty in distinguishing between these often similar forms. The aim of this review was to describe the evolution in our understanding of triphasic waves that has occurred regarding the pathophysiology of triphasic waves, their most frequent causes, and the diagnostic difficulties involved in interpretation and differentiation from nonconvulsive status epilepticus.

SUMMARY Generalized periodic discharges with triphasic morphology were previously referred to as triphasic waves but have now been subsumed into the ACNS classification as generalized periodic discharges. Although triphasic waves and generalized spike-wave complexes may resemble each other and hence may be incorrectly identified in comatose critically ill patients, many authors believe that there are different entities, with definable morphologic and clinical differences attributable to each waveform. The occurrence of both patterns in the same patient is extremely rare with only a single prior case report. Here the authors report a patient with typical triphasic waves and generalized spike-wave complexes and highlight the morphologic and EEG differences between the two patterns. The occurrence of both waveforms in the same EEG recording supports the notion of different cerebral generators and pathways, further differentiating rather than merging these morphologies.

Purpose Triphasic waves (TWs) are defined as high-amplitude positive waveforms with preceding and after-going negative waves, typically seen in medically ill patients. TWs manifest in similar clinical presentations as other EEG encephalopathies; however, electrographically, they appear different. To better understand the difference, the authors used two different source localization software programs to find a reproducible and unique signature for TW. Methods EEGs performed at Johns Hopkins Hospital and Duke University Hospital were retrospectively analyzed. EEG samples of TW, Delta, Theta-Delta, and Frontal Intermittent Rhythmic Delta Activity were selected. The authors did source localization via Commercial Curry 8 and open-source Brainstorm software. A minimum of 10 stereotypical waveforms per subject were selected. The authors used the Boundary Element Method for the head model, which was derived from the Montreal Neurological Institute averaged imaging data set. Dipole and current density analyses were performed. Results Twenty-eight patients were selected (10 TW, 4 Frontal Intermittent Rhythmic Delta Activity, 6 Theta-Delta, and 8 Delta). The findings suggest the activation of anterior frontal and midline structures for TW. Frontal Intermittent Rhythmic Delta Activity had a similar localization but without a moving dipole. In comparison, the Delta and Delta-Theta appeared to have a more diffuse origin. Conclusions Source analysis of TW via two different software suggests the anterior midline location of TW with anterior to posterior propagation. These findings correlate with the previous hypotheses of TW origin. Retrospective analysis, low number of recording electrodes, and difficult analysis of slow waves limit the interpretation of these results. Nonetheless, this article opens the prospect of future studies in this field.

Status epilepticus (SE) is the state of continuous or repetitive seizures, which can occur with or without convulsions. Evolving definitions of SE take into account the concept that neuronal injury may occur at different times in different types of SE.SE that does not respond to initial treatment may become refractory or even super-refractory. Nonconvulsive SE is increasingly recognized in comatose patients in critical care units, with the growing use of continuous electroencephalogram monitoring. SE is a neurologic emergency that carries a high risk of mortality and morbidity.

BACKGROUND AND OBJECTIVES: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as “ictal-interictal-injury continuum” (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC. METHODS: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as “seizure (SZ),” “lateralized periodic discharges (LPDs),” “generalized periodic discharges (GPDs),” “lateralized rhythmic delta activity (LRDA),” “generalized rhythmic delta activity (GRDA),” or “other.” EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability. RESULTS: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Image: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Image: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds. DISCUSSION: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus.

SUMMARY Triphasic waves are EEG phenomena typically seen in patients with acute encephalopathy and have importance in diagnosis and prognosis in these cases. The underlying metabolic disturbances associated with their incidence have been described previously, but neuroimaging characteristics are not well delineated. There are a few small studies that define neuroimaging results in patients with triphasic waves. This review highlights the most common neuroimaging findings in these patients, including subcortical white matter disease, which itself may be a risk factor for triphasic waves.

Purpose:The diagnosis of Postural Orthostatic Tachycardia syndrome traditionally involves orthostatic vitals evaluation. The Compensatory Reserve Index is a non-invasive, FDA-cleared algorithm that analyses photoplethysmogram waveforms in real time to trend subtle waveform features associated with varying degrees of central volume loss, from normovolemia to decompensation. We hypothesised that patients who met physiologic criteria for Postural Orthostatic Tachycardia syndrome would have greater changes in Compensatory Reserve Index with orthostatic vitals.Methods:Orthostatic vitals and Compensatory Reserve Index values were assessed in individuals previously diagnosed with Postural Orthostatic Tachycardia syndrome and healthy controls aged 12–21 years. Adolescents were grouped for comparison based on whether they met heart rate criteria for Postural Orthostatic Tachycardia syndrome (physiologic Postural Orthostatic Tachycardia syndrome).Results:Sixty-one patients were included. Eighteen percent of patients with an existing Postural Orthostatic Tachycardia syndrome diagnosis met heart rate criteria, and these patients had significantly greater supine to standing change in Compensatory Reserve Index (0.67 vs. 0.51; p<0.001). The optimal change in Compensatory Reserve Index for physiologic Postural Orthostatic Tachycardia syndrome was 0.60. Patients with physiologic Postural Orthostatic Tachycardia syndrome were more likely to report previous diagnoses of anxiety or depression (p = 0.054, 0.042).Conclusion:An accurate diagnosis of Postural Orthostatic Tachycardia syndrome may be confounded by related comorbidities. Only 18% (8/44) of previously diagnosed Postural Orthostatic Tachycardia syndrome patients met heart rate criteria. Findings support the utility of objective physiologic measures, such as the Compensatory Reserve Index, to more accurately identify patients with true autonomic dysfunction.

Introduction In women with epilepsy, seizure frequency and severity can be affected during pregnancy by factors such as changes in ASD (anti-seizure drug) metabolism, changes in hormone levels, and medication compliance. Some women with epilepsy experience seizure worsening during pregnancy, while others have an improvement. Most epileptic seizures during pregnancy occur in women with pre-existing epilepsy. Rarely, women develop new-onset seizure-like episodes concerning for epileptic seizures during pregnancy, posing a diagnostic and therapeutic challenge for the physician. Methods To determine the frequency of new-onset seizures during pregnancy and the clinical course of those with new seizures, we performed a retrospective study of all women with concomitant diagnoses of pregnancy and seizures (excluding eclampsia) at the Johns Hopkins Medical Institutions over a five-year period. We calculated the frequency of events concerning for seizures during pregnancy, including first-lifetime events, and classified these events as epileptic seizures or as seizure mimics. For those with epileptic seizures, we followed up with the patient to determine whether seizures recurred in or after pregnancy, and whether treatment with anti-seizure medication was initiated. Results Over a five-year period, 41,869 women received care at Johns Hopkins Medical Institutions during pregnancy. 84 women had at least one event concerning for seizure during their pregnancies. Of these, 11 had no prior history of seizures; 5 of these women were found to have first-time unprovoked epileptic seizures supported by epileptiform abnormalities on EEG. All women delivered at term with no major complications. Four of these women continued to have epileptic seizures after delivery. Conclusions New onset seizures during pregnancy were rare. Most women with first-time epileptic seizures during pregnancy also had epileptic seizures after pregnancy, indicating a first presentation of epilepsy.

Objectives To identify early predictors of postictal delirium in adult patients after termination of status epilepticus. Design Retrospective study. Setting ICUs at a Swiss tertiary academic medical center. Patients Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018. Interventions None. Methods Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation). Measurements and main results Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1-3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53-7.33). Conclusions Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2-3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.

Triphasic waves are EEG phenomena typically seen in patients with acute encephalopathy and have importance in diagnosis and prognosis in these cases. The underlying metabolic disturbances associated with their incidence have been described previously, but neuroimaging characteristics are not well delineated. There are a few small studies that define neuroimaging results in patients with triphasic waves. This review highlights the most common neuroimaging findings in these patients, including subcortical white matter disease, which itself may be a risk factor for triphasic waves.

SUMMARY Generalized periodic discharges with triphasic wave (TW) morphology, long referred to as TWs, are typical of many toxic, metabolic, infectious, and cerebral structural problems, often in concert. Identifying TWs has been challenging for the electroencephalographer and clinician, as has been their cause, significance, prognosis, and treatment. This review highlights the many different patterns of TWs with commentary on their various causes and etiologies, characteristics, different morbidities, differentiation from nonconvulsive status epilepticus, and their prognosis. The articles in this Journal of Clinical Neurophysiology special issue on TWs will review the many challenges the clinician face when TWs are sighted.

SUMMARY Despite many decades of research, controversy regarding the utility of quantitative EEG (qEEG) for the accurate diagnosis of mild traumatic brain injury (mTBI) remains. This guideline is meant to assist clinicians by providing an expert review of the clinical usefulness of qEEG techniques for the diagnosis of mTBI. This guideline addresses the following primary aim: For patients with or without posttraumatic symptoms (abnormal cognition or behavior), does qEEG either at the time of injury or remote from the injury, as compared with current clinical diagnostic criteria, accurately identify those patients with mTBI (i.e., concussion)? Secondary aims included differentiating between mTBI and other diagnoses, detecting mTBI in the presence of central nervous system medications, and pertinence of statistical methods for measurements of qEEG components. It was found that for patients with or without symptoms of abnormal cognition or behavior, current evidence does not support the clinical use of qEEG either at the time of the injury or remote from the injury to diagnose mTBI (level U). In addition, the evidence does not support the use of qEEG to differentiate mTBI from other diagnoses or detect mTBI in the presence of central nervous system medications, and suitable statistical methods do not exist when using qEEG to identify patients with mTBI. Based upon the current literature review, qEEG remains an investigational tool for mTBI diagnosis (class III evidence).

Generalized periodic discharges with triphasic morphology (GPDs + TWm) have been reported with multiple metabolic and drug toxicities. Beta-lactam antibiotics in some cases can cause neurotoxicity with GPDs + TWm on EEG. There are no reports in the literature of aztreonam causing neurotoxicity and GPDs + TWm. Here we describe GPDs + TWm and encephalopathy developing in a patient with underlying dementia and acute kidney injury who was started on aztreonam for cystitis. Neurotoxic effects of beta-lactam antibiotics have been well studied at this point, likely related to GABA receptor antagonism by the beta lactam ring. Risk factors for toxicity include, advanced age, prior neurological injury and decreased renal clearance. This patient carried multiple risk factors for beta-lactam neurotoxicity. Discontinuation of aztreonam led to a resolution of GPDs + TWm on EEG, and regression of encephalopathy.

To understand the genetic basis of complex traits, it is important to be able to efficiently phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have been isolated from diverse populations around the globe and whole-genome sequenced. As a result, hundreds of wild strains with known genome sequences can be used for genome-wide association studies (GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans starvation resistance has not been systematically characterized, and precise measurement of the trait is time-intensive. Here, we developed a population-selection-and-sequencing-based approach to phenotype starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing (RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that increased in frequency over time are starvation-resistant relative to strains that decreased in frequency. Further, we found that variation in starvation resistance is significantly associated with variation at a region on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for starvation resistance. This study demonstrates the feasibility of using population selection and sequencing in an animal model for phenotypic analysis of quantitative traits, documents natural variation of starvation resistance in C. elegans, and identifies a genomic region that contributes to such variation.