Distinction between epileptic and non-epileptic arousal by heart rate change.

OBJECTIVE: We investigated the difference in heart rate (HR) change between epileptic and non-epileptic arousals in adult patients with epilepsy (PWE). METHODS: This is a case-control study conducted at the University Hospitals of Cleveland Medical Center. Inclusion criteria are (1) adult (≥18 years old) PWE who had arousal related to a focal aware or impaired awareness automatism seizure with or without focal to bilateral tonic-clonic seizure during an Epilepsy Monitoring Unit (EMU) admission between January 2009 and January 2021 or (2) adult PWE who had a non-epileptic arousal during an EMU admission between July 2020 and January 2021. Outcomes are (1) a percent change in baseline HR within 60 s after arousal and (2) the highest percent change in baseline HR within a 10-s sliding time window within 60 s after arousal. RESULTS: We included 20 non-epileptic arousals from 20 adult PWE and 29 epileptic arousals with seizures from 29 adult PWE. Within 60 s after arousal, HR increased by a median of 86.7% (interquartile range (IQR), 52.7%-121.3%) in the epileptic arousal group compared to a median of 26.1% (12.9%-43.3%) in the non-epileptic arousal group (p < 0.001). The cut-off value was 48.7%. The area under the curve (AUC), sensitivity, and specificity were 0.85, 0.79, and 0.80, respectively. More than 70.1% was only in the epileptic arousals, with 100% specificity. Within 10 s of the greatest change, HR increased by 36.5 (18.7%-48.4%) in the epileptic arousal group compared to 17.7 (10.9%-23.7%) in the non-epileptic arousal group (p < 0.001). The cut-off value was 36.5%. The AUC, sensitivity, and specificity were 0.79, 0.52, and 0.95, respectively. More than 48.1% was only in the epileptic arousals, with 100% specificity. SIGNIFICANCE: Tachycardia during epileptic arousals was significantly higher and more robust compared to tachycardia during non-epileptic arousals.

Critique of the 2017 epileptic seizure and epilepsy classifications.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.

Proposal: different types of alteration and loss of consciousness in epilepsy.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

Mapping of cingulate motor function by cortical stimulation.

An 8-year-old boy with intractable left mesiofrontal lobe epilepsy underwent placement of stereotactic intracerebral depth electrodes to better localise the epileptogenic zone. Co-registration of preoperative MRI and post-electrode implantation CAT allowed for anatomical localisation of electrode contacts. Electrical stimulation of electrodes over the dorsal and ventral banks of the cingulate cortex on the left produced right foot dorsiflexion and right wrist and elbow flexion, respectively, demonstrating detailed representation of cingulate motor function in humans, somatotopically distributed along the banks of the cingulate sulcus, as seen in the non-human primate. [Published with video sequences].

Bilateral tonic seizures vs. bilateral tonic events in critically ill patients: differences in semiology.

PURPOSE: Our primary aim was to analyze bilateral epileptic tonic seizures (ETS) and bilateral non-epileptic tonic events (NTE) in critically ill patients. Our secondary aim was to analyze ETS per their epileptogenic zone. METHODS: We performed a retrospective analysis of clinical signs in patients with bilateral ETS and NTE. Two authors independently reviewed 34 videos of ETS in 34 patients and 15 videos of NTEs in 15 patients. Initial screening and review was performed in an unblinded manner. Subsequently, the semiology was characterized independently and blindly by a co-author. Statistical analysis was conducted using Bonferroni correction and two-tailed Fischer exact test. Positive predictive value (PPV) was calculated for all signs. Cluster analysis of signs with a PPV >80% was performed to evaluate co-occurring semiological features in the two groups. RESULTS: Compared to patients with ETS, those with NTEs more frequently had predominant involvement of proximal upper extremities (UE) (67% vs. 21%), internal rotation of UE (67% vs. 3%), adduction of UE (80% vs. 6%) and bilateral elbow extension (80% vs. 6%). In contrast, those with ETS more frequently had abduction of UE (82% vs 0%), elevation of UE (91% vs. 33%), open eyelids (74% vs. 20%), and involvement of both proximal and distal UE (79% vs. 27%). In addition, seizures that remained symmetrical throughout were more likely to have a generalized onset than focal (38% vs. 6%), p = 0.032, PPV 86%. CONCLUSIONS: A careful analysis of semiology can often help differentiate between ETS and NTE in the ICU. The combination of eyelids open, upper extremity abduction, and elevation reached a PPV of 100% for ETS. The combination of bilateral arms extension, internal rotation, and adduction reached a PPV of 90.9% for NTE.

Racial and Ethnic Differences in Antiseizure Medications Among People With Epilepsy on Medicaid: A Case of Potential Inequities.

Background and Objectives: Being on a newer, second-, and third-generation antiseizure medication (ASM) may represent an important marker of quality of care for people with epilepsy. We sought to examine whether there were racial/ethnic differences in their use. Methods: Using Medicaid claims data, we identified the type and number of ASMs, as well as the adherence, for people with epilepsy over a 5-year period (2010-2014). We used multilevel logistic regression models to examine the association between newer-generation ASMs and adherence. We then examined whether there were racial/ethnic differences in ASM use in models adjusted for demographics, utilization, year, and comorbidities. Results: Among 78,534 adults with epilepsy, 17,729 were Black, and 9,376 were Hispanic. Overall, 25.6% were on older ASMs, and being solely on second-generation ASMs during the study period was associated with better adherence (adjusted odds ratio: 1.17, 95% confidence interval [CI]: 1.11-1.23). Those who saw a neurologist (3.26, 95% CI: 3.13-3.41) or who were newly diagnosed (1.29, 95% CI: 1.16-1.42) had higher odds of being on newer ASMs. Importantly, Black (0.71, 95% CI: 0.68-0.75), Hispanic (0.93, 95% CI: 0.88-0.99), and Native Hawaiian and Other Pacific Island individuals (0.77, 95% CI: 0.67-0.88) had lower odds of being on newer ASMs when compared with White individuals. Discussion: Generally, racial and ethnic minoritized people with epilepsy have lower odds of being on newer-generation ASMs. Greater adherence by people who were only on newer ASMs, their greater use among people seeing a neurologist, and the opportunity of a new diagnosis point to actionable leverage points for reducing inequities in epilepsy care.

Mirth and laughter elicited during brain stimulation.

There are few reports of laughter and/or mirth evoked by electrical stimulation of the brain. In this study, we present a patient with intractable epilepsy in whom mirth and laughter was consistently produced during stimulation of the left inferior frontal gyrus (opercular part) using stereotactically placed depth electrodes. A review of the literature shows that cortical sites that produce mirth when stimulated are located in the dominant hemisphere close to language areas or cortical negative motor areas.

Burden of Chronic and Acute Conditions and Symptoms in People With Epilepsy.

BACKGROUND AND OBJECTIVES: People with epilepsy, one-third of whom in the United States are on Medicaid, experience a wide range of chronic and physical comorbidities that influence their care and outcomes. In this study, we examine the burden and racial/ethnic disparities of chronic and acute conditions, injuries, and symptoms in a large and diverse group of people with epilepsy on Medicaid. METHODS: Using 5 years of Medicaid claims data, we identified adults with epilepsy and used all available claims and diagnoses to identify each person's Clinical Classification Codes groups diagnosed during the study period. Using association rule mining, we identified the top combinations of conditions and stratified these by race/ethnicity to identify potential prevalence disparities. We examined the top combinations of conditions in high utilizers; that is, individuals in the top quartile of hospitalizations and emergency department visits. RESULTS: Among 81,963 patients, the most common conditions were anxiety and mood disorders (46.5%), hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache (29.5%). When examining combinations of conditions, anxiety and mood disorders continued to have an outsized prevalence, appearing in nearly every combination. There were notable disparities in disease burden, with American Indians and Alaskan Natives having a substantially higher prevalence of developmental disorders, while Black individuals had a higher prevalence of hypertension. These disparities persisted to the higher-order combinations that included these conditions. High utilizers had a much higher disease burden, with 75.8% having an anxiety or mood disorder, as well as a higher burden of injuries. DISCUSSION: This study shows a high prevalence of psychiatric and physical conditions and identifies racial and ethnic disparities affecting people with epilepsy. Targeting interventions to consider the comorbidities, race, and ethnicity has potential to improve clinical care and reduce disparities.

Epileptic seizure semiology in infants and children.

Epileptic seizure semiology adds important information to the formulation of the hypothesis of the epileptogenic zone. Seizure semiology in infants and children are simple and elementary, becoming more complex with maturation of brain. Also in this age group, seizure semiology may be generalized in a setting of a focal lesion or may show focal signs with misleading localization values. We review seizure semiology of patients aged one month to ten years with respect to lateralization and localization of the epileptogenic zone.

Autoimmune musicogenic epilepsy associated with anti-glutamic acid decarboxylase antibodies and Stiff-person syndrome.

Epilepsy should be suspected in patients with Stiff-person syndrome and new onset paroxysmal episodes. Musicogenic epilepsy may be a manifestation of anti-GAD-Ab spectrum, supporting an autoimmune workup in these patients. Appropriate treatment is not well established, and immunotherapy should be considered in patients with only partial response to antiepileptic drugs.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Epidemiologist's view: Addressing the epilepsy surgery treatment gap with minimally-invasive techniques.

Despite the fact that epilepsy surgery is both safe and effective, a considerable "surgical treatment gap" remains in that most persons who are eligible for surgery do not receive it. It has been argued that epilepsy surgery is one of the most underutilized of all accepted medical treatments in the world. In this article, we review the epidemiology of the epilepsy surgery treatment gap, and consider the role minimally-invasive epilepsy surgery may play in reducing this gap.

Electrooculogram and submandibular montage to distinguish different eye, eyelid, and tongue movements in electroencephalographic studies.

OBJECTIVE: We propose an electrooculogram and submandibular montage that helps to discriminate eye/eyelid/tongue movements and to differentiate them from epileptiform activity or slowing on electroencephalography (EEG). METHODS: We analyzed different eye/eyelid and tongue movements in 6 and 4 patients, respectively. Six peri-orbitally and one submandibular electrodes were placed. We referred these electrodes to an indifferent reference (Cz/Pz) and we recorded eye/eyelid and tongue movements simultaneously with the 10-20 system EEG. Additionally, we analyzed 2 seizures with the electrooculogram montage. RESULTS: The electrooculogram deflections always showed an opposite phase direction when eye/eyelid movements occurred. Conversely, epileptiform activity produced deflections in the same phase direction in all electrooculogram electrodes. The electrooculogram montage was able to distinguish eye ictal semiology. Vertical tongue movements showed opposite phase deflections between the submandibular and the inferior ocular electrodes. Horizontal tongue movements revealed opposite phase reversal deflections between both inferior ocular electrodes. CONCLUSIONS: The proposed montage accurately defines different eye/eyelid and tongue movements from brainwave activity. Additionally, it is useful to differentiate eye/eyelid movements from epileptiform activity and to characterize ictal ocular semiology, which can help localize or lateralize the epileptogenic zone. SIGNIFICANCE: We propose this new montage to provide added value to prolonged video-EEG studies.

Epileptic seizure semiology in different age groups.

Seizure semiology provides information about the eloquent cortex involved during a seizure and helps to generate a hypothesis regarding the localization of the epileptogenic zone (EZ), a prerequisite for surgical management of epilepsy. We aimed to study the seizure semiology among all different age groups to better characterize semiological changes that occur with age. We performed a retrospective review of video-EEG data in paediatric and adult patients admitted to the Epilepsy Monitoring Unit over a three-year period. Authors independently reviewed and classified the seizure semiology while blinded to clinical, EEG, and neuroimaging data. A total of 270 patients were included in the study. The most frequent EZ in patients who were one month to three years old was undetermined. Focal epilepsy became more frequent in patients older than 10 years. Among patients with focal epilepsy, a posterior quadrant EZ was most frequent in children younger than three years old, a temporal EZ between three and six years old, and a frontal EZ between six and 10 years old. The temporal lobe was the most frequent location for focal EZ in patients older than 18 years. Auras, automotor seizures, and generalized tonic-clonic seizures were extremely infrequent in patients younger than 10 years old. The youngest patient with auras was 5.7 years old. The youngest patient with automotor seizures was 3.7 years old. We identified only three patients with generalized tonic-clonic seizures who were younger than 10 years (aged six months, 6.6 years, and nine years, respectively). Patients younger than three years exhibited mostly generalized simple motor seizures and hypomotor seizures. Generalized epileptic spasms, generalized tonic seizures, and generalized clonic seizures were infrequent in patients older than 10 years. Seizure semiology and electroencephalographic changes most likely reflect the maturation of cortical functions.

Noninvasive Presurgical Data for One-Stage Leucotomy in Catastrophic Epilepsy.

BACKGROUND: Catastrophic epilepsy results in severe neurodevelopmental delay in infants because of frequent and/or long seizures. Therefore, consideration of early epilepsy surgery is essential for neurodevelopmental outcome. Once an infant with catastrophic seizures is identified as a surgical candidate, it is important that the surgical plan be carefully defined based on detailed presurgical evidence to minimize surgical complications in this age group. CASE DESCRIPTION: We present 2 infants with catastrophic epilepsy, epileptic spasms, and bihemispheric electroencephalographic abnormalities who underwent one-stage disconnection surgery based on a sound hypothesis of the epileptogenic zone. Each patient underwent an extensive noninvasive presurgical investigation followed by stereotactic disconnection leucotomy in a single stage. After the 2 children were followed for 24-36 months. A seizure reduction by at least 90% (Engel class I) was achieved in both cases with subsequent improvement in neurodevelopmental progress. There were no perioperative complications. Both patients had widespread cortical dysplasia on pathologic evaluation. CONCLUSIONS: Careful consideration of the noninvasive presurgical workup can identify focal onset even in the presence of catastrophic epilepsy with widespread bilateral abnormalities. Single-stage lobar leucotomy for disconnection of the epileptogenic zone can lead to excellent outcome in these patients.

Generalized Periodic Discharges With and Without Triphasic Morphology.

PURPOSE: Generalized periodic discharges (GPDs) with a triphasic morphology have been associated with nonepileptic encephalopathies. We conducted the study to assess the reliability in which electroencephalographers can differentiate triphasic from nontriphasic periodic discharges and to evaluate for the presence of electroencephalogram and clinical characteristics that are associated with a higher risk of seizures. METHODS: We studied prospectively 92 patients between May 2016 and February 2017. Each pattern was analyzed by two readers, who were blinded to clinical data. RESULTS: The interrater agreement was "substantial" (Kappa 0.67). The following features significantly increased the risk of developing seizures: the absence of triphasic morphology, focality on electroencephalogram, interburst suppression, a history of epilepsy, and an abnormal scan. The "GPD score" includes a history of epilepsy, focality on electroencephalogram, and the absence of triphasic morphology. A GPD score of 0 has 13% risk of seizures, whereas a score of 5 to 6 has a 94% risk. CONCLUSIONS: Triphasic morphology GPDs confer less risk of seizures when compared with patients with GPDs without triphasic morphology. Features with a higher risk of seizures include focality on electroencephalogram, interburst suppression, a history of epilepsy, and an abnormal scan. The GPD score can be used to assess the risk of developing seizures in patients with GPDs.

Hippocampal transection for stereo-electroencephalography-proven dominant mesial temporal lobe epilepsy in a child: a detailed case report and critical review.

Resection of the hippocampus ipsilateral to the verbal memory-dominant hemisphere frequently results in severe memory deficits. In adults with epilepsy, multiple hippocampal transections (MHTs) have resulted in excellent seizure outcome with preservation of verbal memory. The authors report the first detailed case of a child undergoing MHTs for mesial temporal lobe epilepsy. A 13-year-old right-handed boy had intractable seizures characterized by epigastric discomfort evolving to unresponsiveness and chewing automatisms, lasting 1 minute and occurring 2-3 times weekly, sometimes ending in a generalized tonic-clonic seizure. He had no seizure risk factors and nonfocal examination results. Interictal electroencephalography (EEG) showed frequent left temporal epileptiform discharges (maximum FT9) and intermittent slowing. Video EEG, FDG-PET, and 1.5-T MRI were nonlocalizing. Neuropsychological evaluation suggested left temporal lobe dysfunction. A stereo-EEG investigation using 8 electrodes localized the seizure onset zone to the anterior mesial temporal region, immediately involving the hippocampus. The temporal pole and amygdala were resected en bloc with 3 MHTs. Comparison of neuropsychological tests 4 months before and 6 months after the surgery showed a significant decline only in confrontational naming and no significant change in verbal memory. Six and a half years later, the patient remains seizure free with no antiepileptic drugs. In children with established hemispheric dominance suffering from mesial temporal lobe epilepsy, MHTs may be an option.

A white matter tract mediating awareness of speech.

OBJECTIVE: To investigate the effects of extraoperative electrical stimulation of fiber tracts connecting the language territories. METHODS: We describe results of extraoperative electrical stimulation of stereotactic electrodes in 3 patients with epilepsy who underwent presurgical evaluation for epilepsy surgery. Contacts of these electrodes sampled, among other structures, the suprainsular white matter of the left hemisphere. RESULTS: Aside from speech disturbance and speech arrest, subcortical electrical stimulation of white matter tracts directly superior to the insula representing the anterior part of the arcuate fascicle, reproducibly induced complex verbal auditory phenomena including (1) hearing one's own voice in the absence of overt speech, and (2) lack of perception of arrest or alteration in ongoing repetition of words. CONCLUSION: These results represent direct evidence that the anterior part of the arcuate fascicle is part of a network that is important in the mediation of speech planning and awareness likely by linking the language areas of the inferior parietal and posterior inferior frontal cortices. More specifically, our observations suggest that this structure may be relevant to the pathophysiology of thought disorders and auditory verbal hallucinations.