Nocturnal paroxysmal dystonia to sleep-related hypermotor epilepsy: A critical review.

Sleep-related paroxysmal motor episodes (SPMEs) have been described by various names, including nocturnal paroxysmal dystonia, nocturnal frontal lobe epilepsy (NFLE), and sleep-related hypermotor epilepsy. The underlying pathophysiology has been debated over the years, with these episodes assumed to be a form of paroxysmal dystonia or parasomnia versus a form of epilepsy. In most studies published on SPMEs and their variants (paroxysmal arousals, nocturnal paroxysmal dystonia, and episodic nocturnal wanderings) in the early 1990s, the authors speculated on the pathophysiology but did not commit to one idea. It was not until the mid-1990s that epilepsy became the leading prospect. We performed a narrative review of the major articles that have described this syndrome in a chronological fashion. We identified three eras, 1972-1993, 1994-1998, and 1999 to the present, each era marked by a landmark study. Our critical review of these early studies shows that the neurophysiological data supporting epilepsy as the sole basis for all SPME cases is very weak. In 1994-1995, a familial pattern of this syndrome was described and the term autosomal dominant NFLE was coined, with the authors claiming that all their patients had a form of frontal lobe epilepsy. With the exception of a few reference cases, the neurophysiological evidence that all patients had frontal lobe epilepsy was very weak. Compared to articles published on surgical series of frontal lobe epilepsy, the percentage of SPME cases with positive interictal/ictal electroencephalograms remained very low, seriously questioning the epileptic basis of the syndrome. Our critical review and analysis of the published literature shows that the evidence presented in favor of SPMEs being a homogenous focal epilepsy syndrome is very weak. Neurologists must recognize that SPMEs could be a form of movement disorder, parasomnia, or epilepsy. We recommend a pragmatic semiology-based classification of these episodes using the four-dimensional classification system.

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.

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 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.

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.

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.

Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.

The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the alpha subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a three- to fivefold increase in Ca(2+) sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease.

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%.

Cavernoma-related epilepsy: review and recommendations for management--report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies.

Cerebral cavernous malformations (CCMs) are well-defined, mostly singular lesions present in 0.4-0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM-related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology-specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Accuracy of frame-based stereotactic depth electrode implantation during craniotomy for subdural grid placement.

BACKGROUND: Frame-based stereotaxy and open craniotomy may seem mutually exclusive, but invasive electrophysiological monitoring can require broad sampling of the cortex and precise targeting of deeper structures. OBJECTIVES: The purpose of this study is to describe simultaneous frame-based insertion of depth electrodes and craniotomy for placement of subdural grids through a single surgical field and to determine the accuracy of depth electrodes placed using this technique. METHODS: A total of 6 patients with intractable epilepsy underwent placement of a stereotactic frame with the center of the planned cranial flap equidistant from the fixation posts. After volumetric imaging, craniotomy for placement of subdural grids was performed. Depth electrodes were placed using frame-based stereotaxy. Postoperative CT determined the accuracy of electrode placement. RESULTS: A total of 31 depth electrodes were placed. Mean distance of distal electrode contact from the target was 1.0 ± 0.15 mm. Error was correlated to distance to target, with an additional 0.35 mm error for each centimeter (r = 0.635, p < 0.001); when corrected, there was no difference in accuracy based on target structure or method of placement (prior to craniotomy vs. through grid, p = 0.23). CONCLUSION: The described technique for craniotomy through a stereotactic frame allows placement of subdural grids and depth electrodes without sacrificing the accuracy of a frame or requiring staged procedures.

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.

Parieto-frontal network in humans studied by cortico-cortical evoked potential.

Parieto-frontal network is essential for sensorimotor integration in various complex behaviors, and its disruption is associated with pathophysiology of apraxia and visuo-spatial disorders. Despite advances in knowledge regarding specialized cortical areas for various sensorimotor transformations, little is known about the underlying cortico-cortical connectivity in humans. We investigated inter-areal connections of the lateral parieto-frontal network in vivo by means of cortico-cortical evoked potentials (CCEPs). Six patients with epilepsy and one with brain tumor were studied. With the use of subdural electrodes implanted for presurgical evaluation, network configuration was investigated by tracking the connections from the parietal stimulus site to the frontal site where the maximum CCEP was recorded. It was characterized by (i) a near-to-near and distant-to-distant, mirror symmetric configuration across the central sulcus, (ii) preserved dorso-ventral organization (the inferior parietal lobule to the ventral premotor area and the superior parietal lobule to the dorsal premotor area), and (iii) projections to more than one frontal cortical sites in 56% of explored connections. These findings were also confirmed by the standardized parieto-frontal CCEP connectivity map constructed in reference to the Jülich cytoarchitectonic atlas in the MNI standard space. The present CCEP study provided an anatomical blueprint underlying the lateral parieto-frontal network and demonstrated a connectivity pattern similar to non-human primates in the newly developed inferior parietal lobule in humans.

Modern technology calls for a modern approach to classification of epileptic seizures and the epilepsies.

In the last 10-15 years the ILAE Commission on Classification and Terminology has been presenting proposals to modernize the current ILAE Classification of Epileptic Seizures and Epilepsies. These proposals were discussed extensively in a series of articles published recently in Epilepsia and Epilepsy Currents. There is almost universal consensus that the availability of new diagnostic techniques as also of a modern understanding of epilepsy calls for a complete revision of the Classification of Epileptic Seizures and Epilepsies. Unfortunately, however, the Commission is still not prepared to take a bold step ahead and completely revisit our approach to classification of epileptic seizures and epilepsies. In this manuscript we critically analyze the current proposals of the Commission and make suggestions for a classification system that reflects modern diagnostic techniques and our current understanding of epilepsy.

Upward gaze and head deviation with frontal eye field stimulation.

Using electrical stimulation to the deep, most caudal part of the right frontal eye field (FEF), we demonstrate a novel pattern of vertical (upward) eye movement that was previously only thought possible by stimulating both frontal eye fields simultaneously. If stimulation was started when the subject looked laterally, the initial eye movement was back to the midline, followed by upward deviation. Our finding challenges current view of topological organisation in the human FEF and may have general implications for concepts of topological organisation of the motor cortex, since sustained stimulation also induced upward head movements as a component of the vertical gaze shift. [Published with video sequences].

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.

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.

Hypnopompic seizures.

The relationship between epilepsy and sleep is complex and bidirectional. Ictal awakening is probably a common and well-described phenomenon. In this small observational study we describe arousal from sleep as the only, or at least main, manifestation of some epileptic seizures. We coin the term "hypnopompic seizures" to describe this entity. Five patients with intractable epilepsy were monitored by continuous video-electroencephalogram. Four of them had left temporal lobe epilepsy and one patient had generalised epilepsy. Hypnopompic seizures accounted for 30-100% of their seizure types captured during monitoring. All the seizures occurred during stage II sleep and were brief. Hypnopompic seizures are extremely subtle and may be underdiagnosed and underreported. Future larger studies are needed to shed some light on this unique entity and its neuropathophysiology. Epileptologists should be aware of this type of seizure and careful review of electroencephalograms during the transition from sleep to arousal is imperative to capture these seizures. Physicians, patients and families also need to be aware of such a subtle manifestation of seizures. Improved awareness of hypnopompic seizures and subtle seizures, in general, help guide accurate and early diagnosis, thorough monitoring and appropriate management.