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.

Ictal blinking triggered by isolated spikes as the only manifestation of seizures.

OBJECTIVE: To describe blinking as the only manifestation of seizures from isolated focal and generalized cortical spikes and investigate the relationship between blinks and epileptic discharges. METHODS: We measured the latency from the onset of spikes to the onset of blinks in two patients using electroencephalogram (EEG) and an electrooculogram (EOG), and calculated the median latency in both cases. We analyzed the latency from spike onset to the onset of additional specific eye movements, seen only in the second case. To determine the frequency of spontaneous blinks (not triggered by spikes), we defined a "control point" at 45 s following a random spike for the first case. We tested for statistically significant associations between latencies of blinks (Case 1) as well as between latencies of blinks and specific eye movements (Case 2). RESULTS: A total of 174 generalized spike-waves followed by a blink were analyzed in the first patient. Approximately 61% of the blinks occurred within 150-450 ms after the onset of the spike. Median latency for blinks following a spike was 294 ms compared to 541 ms for control blinks (p = .02). For the second patient, a total of 160 eye movements following a right occipito-parietal spike were analyzed. The median spike-blink latency in the second case was 497 milliseconds. Median latencies of spike onset to contralateral oblique eye movements with blink and left lateral eye movements were 648 and 655 milliseconds, respectively. CONCLUSIONS: Our study shows that isolated cortical spikes can induce epileptic seizures consisting exclusively of blinks. These findings emphasize the importance of careful EEG and EOG analysis to determine blinking as the only ictal phenomenon. We additionally describe a new technique to prove the temporal relationship between cortical discharges and a specific movement when, in addition to the movements triggered by a spike, the same movement is also spontaneously performed by the patient (in this case, blinking).

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.

Stereotactic-EEG-guided radiofrequency multiple hippocampal transection (SEEG-guided-RF-MHT) for the treatment of mesial temporal lobe epilepsy: a minimally invasive method for diagnosis and treatment.

For the treatment of mesial temporal lobe epilepsy on the language-dominant side in patients at high risk of memory decline, we propose a minimally invasive diagnostic and treatment technique, adopting the principles of multiple hippocampal transections (MHT) using stereo-electroencephalography-guided radiofrequency (SEEG-guided-RF-MHT). This new technique allows targeting of the longitudinal fibers in the hippocampus critical for seizure spreading, while sparing the transverse circuits which are considered important for memory processing and avoiding discomfort and longer post-operatory recovery time associated with craniotomies. We report the efficacy and safety of this procedure in a preliminary observational study of cases. Five patients at high risk of memory decline, including three with non-lesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. A new strategy of SEEG electrode placement was used to mimic MHT. After confirming hippocampal seizure onset, all the patients had three linear ablations perpendicular to the amigdalohippocampal complex. The procedure was performed at the patient's bedside with the patient awake during the full length of the procedure. Four out of five patients were seizure-free (average follow up: 14-18 months). There were no associated complications. Visual inspection of brain MRI of patients at six months following SEEG-guided RF-MHT showed significant hippocampal volume preservation. Subjects who received the procedure in the dominant side reported no subjective memory complaints in the follow-up clinic assessments at six months. Our preliminary seizure outcome seems very promising since the majority of our patients (four out of five patients) were seizure-free. Since no lesions are made outside the amygdalo-hippocampal complex using this technique and the temporal stem remains intact, more favorable memory and language outcome is expected in patients at high risk of memory decline.

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".

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.

Classification of paroxysmal events and the four-dimensional epilepsy classification system.

This educational review describes the classification of paroxysmal events and a four-dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non-epileptic paroxysmal events. Non-epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to classify epileptic paroxysmal events: ictal semiology, the epileptogenic zone, etiology, and comorbidities. Efforts are made to keep these four dimensions as independent as possible. The review also includes 12 educational vignettes and three more detailed case reports classified using the 2017 classification of the ILAE and the four-dimensional epilepsy classification. In addition, a case is described which is classified using the four-dimensional epilepsy classification with different degrees of precision by an emergency department physician, a neurologist, and an epileptologist. [Published with video sequences on www.epilepticdisorders.com].

Recurrent focal seizures as a feature of status epilepticus presenting as a peri-ictal water drinking.

We report a case of focal status epilepticus (SE) associated with peri-ictal water drinking (PIWD) behavior in a nine-year-old left-handed boy with epilepsy. We reviewed prior cases of epileptic peri-ictal water drinking. Only one adult patient with status epilepticus and PIWD has been reported previously. This is the first reported case of PIWD SE in a pediatric patient with frontal lobe epilepsy. We found PIWD to have no lateralizing value.

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.

Resection of Temporal Neocortex During Multiple Hippocampal Transections for Mesial Temporal Lobe Epilepsy Does not Affect Seizure or Memory Outcome.

BACKGROUND: Multiple hippocampal transection (MHT) is a surgical treatment for mesial temporal lobe epilepsy associated with improved postoperative neuropsychological outcomes compared with lobectomy. OBJECTIVE: To determine whether resection of the amygdala and anterior temporal neocortex during MHT affects postoperative seizure/memory outcome. METHODS: Seventeen patients with normal magnetic resonance imaging and stereo-electroencephalogram-proven drug-resistant dominant mesial temporal lobe epilepsy were treated with MHT. Nine patients underwent MHT alone (MHT-) and 8 patients underwent MHT plus removal of the amygdala and anterior 4.5 cm of temporal neocortex lateral to the fusiform gyrus (MHT+). Verbal and visual-spatial memory were assessed in all patients preoperatively and in 14 patients postoperatively using the Wechsler Memory Scale. Postoperative seizure control was assessed at 12 months for all patients. RESULTS: Overall, 11 of 17 patients (64.7%) were Engel class 1 at 1 year (6/9 MHT-, 5/8 MHT+, P = .38), and 10 of 14 patients (71.4%) had no significant postoperative decline in either verbal or visual memory (6/8 MHT-, 4/6 MHT+, P = .42). Verbal memory declined in 2 of 8 MHT- and 1 of 6 MHT+ patients, and visual memory declined in 1 of 8 MHT- and 2 of 6 MHT+ patients. Two patients had improved visual memory postoperatively, both in the MHT+ group. CONCLUSION: MHT on the dominant side is associated with high rates of seizure freedom and favorable memory preservation outcomes regardless of the extent of neocortical resection. Preservation of the temporal neocortex and amygdala during MHT does not appear to decrease the risk of postoperative memory decline, nor does it alter seizure outcome.

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

PURPOSE: The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. METHODS: Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. RESULTS: Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). CONCLUSIONS: Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy.