Semiology and Neurophysiology of Clonic Seizures: A Report of 39 Patients.

Background and Objectives: Clonic seizures are currently defined as repetitive and rhythmic myoclonic contractions of a specific body part, producing twitching movements at a frequency of 0.2-5 Hz. There are few studies in the literature that have reported a detailed analysis of the semiology, neurophysiology, and lateralizing value of clonic seizures. In this article, we aim to report our findings from a retrospective review of 39 patients. Methods: We identified 39 patients (48 seizures) from our center who had been admitted with clonic seizures between 2016 and 2022. We performed a retrospective review of their video-EEG recordings for semiology and ictal EEG findings. Seventeen patients also had simultaneous surface-EMG (sEMG) electrodes placed on affected body parts, which were analyzed as well. Results: The most common initial affected body parts were face, arm, and hand. In most of the cases, seizures propagated from lower face to upper face and distal hand to proximal arm. The most common seizure-onset zone was the perirolandic region, and the most common EEG seizure pattern was paroxysmal rhythmic monomorphic activity. The lateralizing value for EEG seizure onset to contralateral hemisphere in unilateral clonic seizures (n = 39) was 100%. All seizures recorded with sEMG electrodes demonstrated synchronous brief tetanic contractions of agonists and antagonists, alternating with synchronous silent periods. Arrhythmic clonic seizures were associated with periodic epileptiform discharges on the EEG, whereas rhythmic clonic seizures were associated with paroxysmal rhythmic monomorphic activity. Overall, the most common etiology was cerebrovascular injuries, followed by tumors. Discussion: Clonic seizures are characterized by synchronized brief tetanic contractions of agonist and antagonistic muscles alternating with synchronized silent periods, giving rise to the visible twitching. The most common seizure onset zone is in the perirolandic region, which is consistent with the symptomatogenic zone being in the primary motor area. The lateralizing value of unilateral clonic seizures for seizure onset in the contralateral hemisphere is 100%.

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.

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.

Spectrum of motor responses elicited by electrical stimulation of primary motor cortex: A polygraphic study in patients with epilepsy.

OBJECTIVE: To study the neurophysiology of motor responses elicited by electrical stimulation of the primary motor cortex. METHODS: We studied motor responses in four patients undergoing invasive epilepsy monitoring and functional cortical mapping via electrical cortical stimulation using surface EMG electrodes. In addition, polygraphic analysis of intracranial EEG and EMG during bilateral tonic-clonic seizures, induced by cortical stimulation, was performed in two patients. RESULTS: (a) Electrical cortical stimulation: The motor responses were classified as clonic, jittery, and tonic. The clonic responses were characterized by synchronous EMG bursts of agonist and antagonistic muscles, alternating with silent periods. At stimulation frequencies of <20 Hz, EMG bursts were of ≤50 ms duration (Type I clonic). At stimulation frequencies of 20-50 Hz, EMG bursts were of >50 ms duration and had a complex morphology (Type II clonic). Increasing the current intensity at a constant frequency converted clonic responses into jittery and tonic contractions. (b) Bilateral tonic-clonic seizures: The intracranial EEG showed continuous fast spiking activity during the tonic phase along with interference pattern on surface EMG. The clonic phase was characterized by a polyspike-and-slow wave pattern. The polyspikes were time-locked with the synchronous EMG bursts of agonists and antagonists and the slow waves were time-locked with silent periods. INTERPRETATION: These results suggest that epileptic activity involving the primary motor cortex can produce a continuum of motor responses ranging from type I clonic, type II clonic, and tonic responses to bilateral tonic-clonic seizures. This continuum is related to the frequency and intensity of the epileptiform discharges with tonic seizures representing the highest end of the spectrum.

A descriptive study of eye and head movements in versive seizures.

BACKGROUND: Versive seizures, consisting of forced, involuntary, sustained and unnatural turning of eyes and head toward one side, lateralize to the hemisphere contralateral to the direction of the eye and head turn. The characteristics of eye and head movements in version have been rarely and incompletely studied in spontaneous epileptic seizures as opposed to direct cortical stimulation studies. METHODS: We performed a single center retrospective analysis of a cohort of 28 patients with 43 seizures, who had been admitted to the adult epilepsy monitoring unit at University Hospitals Cleveland Medical Center between January 2009 and August 2020. We only included patients with clear, high-resolution seizure videos and interpretable EEG. RESULTS: The eye movements were conjugate and contralateral to the hemisphere of seizure onset in 100% of the focal-onset seizures. The eye movements were saccadic in 89.3% with a predominant vector in oblique upward direction in 86.8% of the seizures. Head deviation was present in 100% of the seizures and the eyes and head deviated in the same direction in 97.6% of the seizures. In addition to deviation along the horizontal meridian, there was a vertical component to the head deviation as well, as evidenced by movement of the chin upward along the vertical axis in 93% of the seizures, thus indicating strong activation of the sternocleidomastoid muscle ipsilateral to the hemisphere of seizure onset. Concomitant facial motor activity ipsilateral to the direction of version was seen in 93% of the seizures. The most common pattern was a clonic superimposed on tonic facial contraction. DISCUSSION: Version remains a reliable and highly lateralizing sign. The majority of the eye movements during version occur in a saccadic fashion rather than one smooth movement, mostly in an oblique upward direction. Head deviation is very closely associated with eye deviation, thus indicating a common symptomatogenic zone for both, which is most likely the frontal eye field. A high concurrence of ipsilateral facial motor activity with version is likely because of close proximity of the frontal eye field to the face area in the primary motor cortex.

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.

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.

Ictal motor sequences: Lateralization and localization values.

OBJECTIVE: To determine the lateralization and localization values of ictal motor sequences in the setting of focal epilepsy ending with a secondarily generalized motor seizure. METHODS: Retrospectively, the ictal motor sequences were analyzed in patients with focal epilepsy ending with a secondarily generalized motor seizure by three readers blinded to all clinical and electrographic data. One representative seizure per patient was selected. Prevalence, positive predictive value (PPV), and Fleiss Kappa for the following motor signs were calculated: version, unilateral limb tonic posturing, unilateral limb clonic seizure, figure-of-4, M2e, hand dystonia, clonic asymmetric ending, and Todd's paralysis. Sequences of signs with a PPV ≥ 80% were then analyzed to determine their lateralization and localization values. RESULTS: A total of 47 seizures were studied. The "reliable" motor signs with a robust lateralizing value (PPV > 80%) were version, unilateral tonic posturing, M2e, unilateral clonic seizure, asymmetric clonic ending, and Todd's paralysis. Figure-of-4 and hand dystonia had a relatively low PPV, and therefore were not included in the following sequence analysis, which included only 38 patients with two or more motor signs of high PPV. Multiple combinations of temporal progression of motor signs were seen in these 38 patients, with version being the most common initial motor sign (29 of 38 patients) usually followed by M2e (15 of 29 patients), and/or a focal tonic seizure (7 of 29 patients). Accurate lateralization of the epileptogenic zone (EZ) with a PPV of 100% can be predicted when two or more reliable motor signs point to the same side. However, the various sequences of reliable motor signs did not differentiate between temporal and extratemporal epilepsy. SIGNIFICANCE: The presence of reliable ictal motor signs in focal epilepsy is extremely valuable in lateralizing the EZ, but not in determining the localization of the EZ. This is especially useful when epilepsy surgery is indicated.

Homotopic reciprocal functional connectivity between anterior human insulae.

The aim of this study was to investigate functional connectivity between right and left insulae in the human brain. We studied a patient with implanted depth electrodes for epilepsy surgery evaluation with stereotactically placed symmetric depth electrodes in both insulae. Bipolar 1 Hz electrical stimulation of the right and left posterior short gyri in the anterior insula evoked responses in the contralateral insular structures. These responses showed a latency of 8-24 ms. This report demonstrates for the first time bi-directional homotopic and heterotopic functional connectivity between right and left anterior insulae. The short latency of the evoked responses suggests mono- or oligo-synaptic connections, most likely via the corpus callosum.

Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases.

Memory loss after brain injury can be a source of considerable morbidity, but there are presently few therapeutic options for restoring memory function. We have previously demonstrated that burst stimulation of the fornix is able to significantly improve memory in a rodent model of traumatic brain injury. The present study is a preliminary investigation with a small group of cases to explore whether theta burst stimulation of the fornix might improve memory in humans. Four individuals undergoing stereo-electroencephalography evaluation for drug-resistant epilepsy were enrolled. All participants were implanted with an electrode into the proximal fornix and dorsal hippocampal commissure on the language dominant (n = 3) or language non-dominant (n = 1) side, and stimulation of this electrode reliably produced a diffuse evoked potential in the head and body of the ipsilateral hippocampus. Each participant underwent testing of verbal memory (Rey Auditory-Verbal Learning Test), visual-spatial memory (Medical College of Georgia Complex Figure Test), and visual confrontational naming (Boston Naming Test Short Form) once per day over at least two consecutive days using novel test forms each day. For 50% of the trials, the fornix electrode was continuously stimulated using a burst pattern (200 Hz in 100 ms trains, five trains per second, 100 µs, 7 mA) and was compared with sham stimulation. Participants and examiners were blinded to whether stimulation was active or not, and the order of stimulation was randomized. The small sample size precluded use of inferential statistics; therefore, data were analysed using descriptive statistics and graphic analysis. Burst stimulation of the fornix was not perceived by any of the participants but was associated with a robust reversible improvement in immediate and delayed performance on the Medical College of Georgia Complex Figure Test. There were no apparent differences on either Rey Auditory-Verbal Learning Test or Boston Naming Test. There was no apparent relationship between performance and side of stimulation (language dominant or non-dominant). There were no complications. Preliminary evidence in this small sample of patients with drug-resistant epilepsy suggests that theta burst stimulation of the fornix may be associated with improvement in visual-spatial memory.

Paroxysmal non-epileptic events in infants and toddlers: A phenomenologic analysis.

AIM: The aim of this study was to analyze in detail the clinical phenomenology of paroxysmal non-epileptic events (PNEE) in infants and toddlers. METHODS: We studied all children aged ≤2 years who were diagnosed with PNEE based on video-electroencephalographic (VEEG) recordings. We analyzed the following four clinical domains of each clinical event: (i) motor manifestations (body/limb jerking, complex motor, and asymmetric limb posturing); (ii) oral/vocal (crying, vocalization, sighing); (iii) behavioral change (arrest of activity, staring); (iv) and autonomic (facial flushing, breath holding). RESULTS: Thirty-one of 81 (38.3%) infants and toddlers had 38 PNEE recorded during the study period (12 girls and 19 boys, mean age 10.5 months). The predominant clinical features were as follows: motor in 26/38 events, oral/verbal in 14/38 events, behavioral in 11/38 events, and autonomic in 8/38 events. Epileptic seizures and PNEE coexisted in four children (12.9%). Seventeen children (54.8%) had one or more risk factors suggestive of epilepsy. Twelve children (38.7%) had a normal neurologic examination, 10 (32.3%) had developmental delay, and eight (25.8%) had a family history of epilepsy or seizures. CONCLUSION: VEEG recorded PNEE in nearly 40% of 81 infants and toddlers referred for unclear paroxysmal events in our cohort. Non-epileptic staring spells and benign sleep myoclonus were the most common events recorded, followed by shuddering attacks and infantile masturbation. In addition, greater than one-half of the infants and toddlers had risk factors, raising a concern for epilepsy in the family and prompting the VEEG evaluation, suggesting that paroxysmal non-epileptic seizures may frequently coexist in young children with epilepsy.

Functional connectivity between right and left mesial temporal structures.

The aim of this study is to investigate functional connectivity between right and left mesial temporal structures using cerebrocerebral evoked potentials. We studied seven patients with drug-resistant focal epilepsy who were explored with stereotactically implanted depth electrodes in bilateral hippocampi. In all patients cerebrocerebral evoked potentials evoked by stimulation of the fornix were evaluated as part of a research project assessing fornix stimulation for control of hippocampal seizures. Stimulation of the fornix elicited responses in the ipsilateral hippocampus in all patients with a mean latency of 4.6 ms (range 2-7 ms). Two patients (29 %) also had contralateral hippocampus responses with a mean latency of 7.5 ms (range 5-12 ms) and without involvement of the contralateral temporal neocortex or amygdala. This study confirms the existence of connections between bilateral mesial temporal structures in some patients and explains seizure discharge spreading between homotopic mesial temporal structures without neocortical involvement.

Treatment of Focal Status Epilepticus plus Epileptic Spasms with Leukotomy in an Infant with TSC 1 Mutation: A Case Study.

BACKGROUND: Focal status epilepticus and catastrophic epilepsy are not rare in infants. Epilepsy surgery can be safely done in selected infants to cure epilepsy. PATIENT DESCRIPTION: We report on an infant who began having drug-resistant status epilepticus at 2 weeks of age and developed epileptic spasms. We discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives. METHOD: Presurgical evaluation consisted of 32-channel scalp video EEG using the standard 10-20 system of electrodes, 3-Tesla brain magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. The surgery consisted of resection of the extensive epileptogenic lesion, in addition to disconnection of the left frontal lobe anterior to the motor strip. RESULT: The infant underwent epilepsy surgery at three months of age. At two-year follow up, she remained seizure free, with no focal motor deficit and the epileptic encephalopathy resolved. The disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue. CONCLUSION: We highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy. In the process, we demonstrate how epileptic spasms, although clinically and electrographically generalized, resolved after disconnecting the epileptogenic zone.

A method for the inclusion of sphenoidal electrodes in realistic EEG source imaging.

SUMMARY: Although EEG source imaging (ESI) has become more popular over the last few years, sphenoidal electrodes (SPE) have never been incorporated in ESI using realistic head models. This is in part because of the true locations of these electrodes are not exactly known. In this study, we demonstrate the feasibility of determining the true locations of SPE and incorporating this information into realistic ESI. The impact of including these electrodes in ESI in mesial temporal lobe epilepsy is also discussed. Seventeen patients were retrospectively selected for this study. To determine the positions of SPE in each case, two orthogonal x-rays (sagittal and coronal) of the SPE needle stilette were taken in the presence of previously digitized scalp electrodes. An in-house computer program was then used to find the locations of the tip of the needle stilette relative to the surface electrodes. These locations were then incorporated in a realistic head model based on the finite element method. EEG source imaging was then performed using averaged spikes for included patients suspected of having mesial temporal lobe epilepsy. Including SPE significantly shifted the ESI result even in the presence of subtemporal electrodes, resulting in an inferior and mesial displacement.

Role of ictal baseline shifts and ictal high-frequency oscillations in stereo-electroencephalography analysis of mesial temporal lobe seizures.

OBJECTIVE: To assess the role of ictal baseline shifts (IBS) and ictal high-frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS). METHODS: We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy-five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs. RESULTS: IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty-seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive pole at the posterior/lateral part of the A-H complex. SIGNIFICANCE: The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics.