Masud Seyal

Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units (MORTEMUS): A Retrospective Study.

BACKGROUND Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING Commission of European Affairs of the International League Against Epilepsy.

Ictal hypoxemia in localization-related epilepsy: analysis of incidence, severity and risk factors

Ictal hypoxemia has been reported in small series of cases and may contribute to sudden unexpected death in epilepsy (SUDEP). We sought to determine the incidence and severity of ictal hypoxemia in patients with localization-related epilepsy undergoing in-patient video-EEG telemetry. We examined whether seizure-associated oxygen desaturation was a consequence of hypoventilation and whether factors such as seizure localization and lateralization, seizure duration, contralateral spread of seizures, patient position at seizure onset and body mass index influenced ictal-related hypoxemia. A total of 304 seizures with accompanying oxygen saturation data were recorded in 56 consecutive patients with intractable localization-related epilepsy; 51 of 304 seizures progressed to generalized convulsions. Pulse oximetry showed oxygen desaturations below 90% in 101 (33.2%) of all seizures with or without secondary generalization, with 31 (10.2%) seizures accompanied by desaturations below 80% and 11 (3.6%) seizures below 70%. The mean duration of desaturation below 90% was 69.2 +/- 65.2 s (47; 6-327). The mean oxygen saturation nadir following secondary generalization was 75.4% +/- 11.4% (77%; 42-100%). Desaturations below 90% were significantly correlated with seizure localization [P = 0.005; odds ratio (OR) of temporal versus extratemporal = 5.202; 95% CI = (1.665, 16.257)], seizure lateralization [P = 0.001; OR of right versus left = 2.098; 95% CI = (1.078, 4.085)], contralateral spread of seizures [P = 0.028; OR of contralateral spread versus no spread = 2.591; 95% CI = (1.112, 6.039)] and gender [P = 0.048; OR of female versus male = 0.422; 95% CI = (0.179, 0.994)]. In the subset of 253 partial seizures without secondary generalized convulsions, 34.8% of seizures had desaturations below 90%, 31.8% had desaturations below 80% and 12.5% had desaturations below 70%. The degree of desaturation was significantly correlated with seizure duration (P = 0.001) and with electrographic evidence of seizure spread to the contralateral hemisphere (P = 0.003). Central apnoeas or hypopnoeas occurred with 50% of 100 seizures. Mixed or obstructive apnoeas occurred with 9% of these seizures. End-tidal carbon dioxide (ETCO2) was recorded in seven patients (19 seizures). The mean increase in ETCO2 from preictal baseline was 18.6 +/- 17.7 mm Hg (13.2; 2.8-77.8). In these 19 seizures, all oxygen desaturations below 85% were accompanied by an increase in ETCO2. Ictal hypoxemia occurs often in patients with localization-related epilepsy and may be pronounced and prolonged; even with seizures that do not progress to generalized convulsions. Oxygen desaturations are accompanied by increases in ETCO2, supporting the assumption that ictal oxygen desaturation is a consequence of hypoventilation. Ictal hypoxemia and hypercapnia may contribute to SUDEP.

Transcranial magnetic stimulation of left prefrontal cortex impairs working memory

OBJECTIVES Several lines of evidence suggest that the prefrontal cortex is involved in working memory. Our goal was to determine whether transient functional disruption of the dorsolateral prefrontal cortex (DLPFC) would impair performance in a sequential-letter working memory task. METHODS Subjects were shown sequences of letters and asked to state whether the letter just displayed was the same as the one presented 3-back. Single-pulse transcranial magnetic stimulation (TMS) was applied over the DLPFC between letter presentations. RESULTS TMS applied over the left DLPFC resulted in increased errors relative to no TMS controls. TMS over the right DLPFC did not alter working memory performance. CONCLUSION Our results indicate that the left prefrontal cortex has a crucial role in at least one type of working memory.

Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: report on two deaths in video-EEG-monitored patients.

Sudden unexplained death in epilepsy (SUDEP) is a common cause of death in patients with epilepsy, with cardiorespiratory dysfunction and a primary cessation of cerebral function proposed as causes. We report two cases of SUDEP in patients with intractable temporal lobe epilepsy undergoing video‐EEG (electroencephalography) telemetry at two centers. Both had secondarily generalized convulsions. EEG, electrocardiography (ECG), and respiratory changes in these two patients are reported herein. Ictal/postictal hypoventilation may contribute to SUDEP with the resulting hypoxemia and acidosis leading to failure of recovery of cortical function and eventual cardiac failure.

Respiratory changes with seizures in localization‐related epilepsy: Analysis of periictal hypercapnia and airflow patterns

Purpose:  The rate of sudden unexpected death in epilepsy (SUDEP) approaches 9 per 1,000 patient‐years in patients with refractory epilepsy. Respiratory causes are implicated in SUDEP. We reported that ictal hypoxemia occurs in one‐third of seizures in localization‐related epilepsy. We now report on respiratory changes in the ictal/postictal period including changes in end‐tidal CO2 (ETCO2) that correlate directly with alveolar CO2, allowing a precise evaluation of seizure‐related respiratory disturbances.

Mechanisms of signal change during intraoperative somatosensory evoked potential monitoring of the spinal cord.

Summary In scoliosis surgery, intraoperative somatosensory evoked potential (SSEP) monitoring has reduced the incidence of postoperative neurologic deficits. Many factors affect the amplitude and latency of SSEP waveforms during surgery. Somatosensory evoked potential amplitude decreases with ischemia and anoxia because of temporal dispersion of the afferent volley and conduction block in damaged axons. In conjunction with surgical manipulations, minor drops in blood pressure may result in substantial SSEP changes that reverse when perfusion pressure is increased. Irreversible anoxic injury to central nervous system white matter with loss of SSEP waveforms is dependent on calcium influx into the intracellular space. Somatosensory evoked potential monitoring may be less sensitive for detecting acute insults in the presence of preexisting white matter lesions. Increased extracellular potassium from acute baro-trauma can block axonal conduction transiently even when there is no axonal disruption. Marked temperature-related drops in SSEP amplitude may occur after exposure of the spine but before instrumentation and deformity correction. Hypothermia may increase false-negative outcomes. Short-interval double-pulse stimulation may improve the sensitivity of the SSEP in detecting early ischemic changes. For neurosurgical procedures on the spinal cord the use of SSEP monitoring in improving postoperative outcome is less well established.

Impact of periictal interventions on respiratory dysfunction, postictal EEG suppression, and postictal immobility

Purpose:  Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy‐related mortality. Seizure‐related respiratory dysfunction (RD), the duration of postictal generalized electroencephalography (EEG) suppression (PGES), and duration of postictal immobility (PI) may be important in the pathophysiology of SUDEP. Periictal interventions may reduce the risk of SUDEP.

Ictal apnea linked to contralateral spread of temporal lobe seizures: Intracranial EEG recordings in refractory temporal lobe epilepsy

Purpose:  Respiratory mechanisms are implicated in sudden unexpected death in epilepsy (SUDEP). We previously demonstrated a high incidence of ictal hypoxemia in temporal lobe seizures. We now report on the temporal relationship between ictal apnea and seizure onset and spread in patients undergoing video‐EEG (electroencephalography) telemetry (VET) with intracranial electrodes.

Suppression of cutaneous perception by magnetic pulse stimulation of the human brain

We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex.

Postictal generalized EEG suppression is linked to seizure‐associated respiratory dysfunction but not postictal apnea

Purpose:  The relationship of postictal generalized electroencephalography (EEG) suppression (PGES) with sudden unexpected death in epilepsy (SUDEP) is controversial. It has been suggested that PGES is associated with respiratory inhibition leading to SUDEP, but the relationship between PGES and respiratory depression is unknown. Respiratory rate and amplitude of airflow increase following seizures but there is persistent hypercapnia and hypoxemia.