Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy.

OBJECTIVE: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy. METHOD: We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of ≥ 1 neural autoantibody (n = 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6- to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency. RESULTS: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p = 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%). CONCLUSIONS: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control.

From the American Epilepsy Society 2009 Annual Course. Non-substrate-directed epilepsy and surgery: PRO and CON.

The surgical treatment of epilepsy is the most efficacious therapeutic modality for patients with a medically refractory partial seizure disorder. Epilepsy surgery has been demonstrated to be both effective and well tolerated in individuals with medial temporal lobe epilepsy associated with mesial temporal sclerosis. The identification of an MRI pathological substrate may be useful in identifying the epileptogenic zone and the appropriate operative strategy, and is predictive of the long-term seizure outcome. Patients with a non-substrate-directed partial epilepsy often require a more rigorous presurgical evaluation because of issues regarding the lateralization and localization of the epileptic brain tissue. The surgical outcome may be most disappointing in individuals with localization-related epilepsy of extratemporal origin associated with a normal MRI study. The present discussion focuses on the selection of patients with extratemporal non-substrate-directed epilepsy for a presurgical evaluation. The important factors associated with an improved quality of life subsequent to epilepsy surgery include seizure remission and avoidance of operation-induced adverse effects.

Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy.

BACKGROUND: Long QT syndrome (LQTS) typically presents with syncope, seizures, or sudden death. Patients with LQTS have been misdiagnosed with a seizure disorder or epilepsy and treated with antiepileptic drug (AED) medication. The gene, KCNH2, responsible for type 2 LQTS (LQT2), was cloned originally from the hippocampus and encodes a potassium channel active in hippocampal astrocytes. We sought to test the hypothesis that a "seizure phenotype" was ascribed more commonly to patients with LQT2. METHODS: Charts were reviewed for 343 consecutive, unrelated patients (232 females, average age at diagnosis 27 +/- 18 years, QTc 471 +/- 57 msec) clinically evaluated and genetically tested for LQTS from 1998 to 2006 at two large LQTS referral centers. A positive seizure phenotype was defined as the presence of either a personal or family history of seizures or history of AED therapy. RESULTS: A seizure phenotype was recorded in 98/343 (29%) probands. A seizure phenotype was more common in LQT2 (36/77, 47%) than LQT1 (16/72, 22%, p < 0.002) and LQT3 (7/28, 25%, p < 0.05, NS). LQT1 and LQT3 combined cohorts did not differ significantly from expected, background rates of a seizure phenotype. A personal history of seizures was more common in LQT2 (30/77, 39%) than all other subtypes of LQTS (11/106, 10%, p < 0.001). CONCLUSIONS: A diagnostic consideration of epilepsy and treatment with antiepileptic drug medications was more common in patients with LQT2. Like noncardiac organ phenotypes observed in other LQTS-susceptibility genes such as KCNQ1/deafness and SCN5A/gastrointestinal symptoms, this novel LQT2-epilepsy association raises the possibility that LQT2-causing perturbations in the KCNH2-encoded potassium channel may confer susceptibility for recurrent seizure activity.

Psychiatric co-morbidity in 75 patients undergoing epilepsy surgery: lack of correlation with pathological findings.

BACKGROUND: Psychiatric disorders may occur in patients with intractable partial epilepsy after surgical treatment. Previous reports attributed the presence of psychological adverse events to specific pathological entities such as dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas. The rationale for the present study is to evaluate the importance of the surgical pathology in individuals undergoing epilepsy surgery. METHODS: The patients were separated into three groups based on the surgical pathology: group I ganglioglioma (N=25), group II DNETs (N=25), and group III mesial temporal sclerosis (N=25). Thirteen of the 75 patients (17.3%) had a preexisting psychiatric disorder. The most common preoperative psychiatric diagnosis was depression (N=4). Sixty-three of the lesions (84%) were restricted to the temporal lobe. The operative strategy included resection of the lesion and epileptogenic cortex. Sixty-two of the 75 patients (83%) were rendered seizure-free. RESULTS: Eight of the 75 patients (10.7%) had an acquired psychiatric illness following surgical treatment. A mood disorder developed in three patients after surgery. No statistical difference emerged in preoperative psychiatric co-morbidity (no group difference; p=1.0) or in newly diagnosed postoperative psychiatric disease (group I vs. II, p=0.67; group I vs. III, p=1.0; and group II vs. III, p=0.67) within the three surgical pathology groups. CONCLUSION: This study indicates that the presence of psychiatric disease before and after surgery for intractable partial epilepsy, predominantly of temporal lobe origin, was independent of the pathological findings.

Recurrence of afebrile status epilepticus in a population-based study in Rochester, Minnesota.

OBJECTIVE: To determine the risk of recurrence of status epilepticus (SE) in a population-based sample and to identify risk factors for recurrence. METHODS: We ascertained all first episodes of afebrile SE in residents of Rochester, MN, through the Rochester Epidemiology Project's records-linkage system between January 1, 1965, and December 31, 1984. Information was collected on age, gender, duration, seizure type, etiology, therapeutic response to initial antiepileptic drug medication, and subsequent episodes of SE. RESULTS: Among the 183 episodes of first afebrile SE, the risk of recurrent SE was 31.7% over a 10-year follow-up period. The risk of recurrence was about 25% for those with acute symptomatic SE, remote symptomatic SE, and idiopathic cryptogenic SE. Recurrence was 100% for those with progressive symptomatic SE. Female gender (rate ratio [RR] = 2.3, 95% CI = 1.1 to 5.0) and progressive symptomatic etiology (RR = 2.4, 95% CI = 0.6 to 8.9) increased the risk for recurrent SE. Both partial SE (RR = 0.5, 95% CI = 0.2 to 1.1) and good therapeutic response to the initial antiepileptic drug therapy (RR = 0.3, 95% CI = 0.1 to 0.7) were associated with a decreased risk of recurrent SE. CONCLUSIONS: Status epilepticus (SE) recurs in about one-third of individuals with a first episode of SE. Except for SE occurring in the setting a progressive brain disorder, the risk of recurrence is about 25%, regardless of the underlying etiology. Female gender and lack of response to the first antiepileptic drug medication after the initial episode of SE identify those individuals at greatest risk for recurrence.

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia.

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.

Adult-onset epilepsy in focal cortical dysplasia of Taylor type.

Focal cortical dysplasia of Taylor type (FCDT) usually presents with seizures at an early age, whereas adult onset of epilepsy is uncommon. We reviewed the medical records of 213 patients with FCDT. In 21 patients (10%), age at seizure onset ranged from 18 to 55 years (mean 25.3). The outcome of seizures in patients with FCDT and adult-onset epilepsy seems favorable vs childhood-onset seizures.

Resective reoperation for failed epilepsy surgery: seizure outcome in 64 patients.

OBJECTIVE: To determine the surgical outcome and factors of predictive value in patients undergoing reoperation for intractable partial epilepsy. METHODS: The authors retrospectively studied the operative outcome in 64 consecutive patients who underwent reoperation for intractable partial epilepsy. Demographic data, results of comprehensive preoperative evaluations, and the seizure and neurologic outcome after reoperation were determined. All patients were followed a minimum of 1 year subsequent to their last operative procedure. RESULTS: Fifty-three patients had two surgeries, and 11 patients had three or more operations. The first surgery involved a lesionectomy (n = 33), "nonlesional" temporal lobe resection (n = 28), and a "nonlesional" extratemporal resection (n = 3). The mean duration between the first and second procedure was 5.5 years. Fifty-five patients underwent an intralobar reoperation, whereas nine had a resection of a different lobe. After reoperation, 25 patients (39%) were free of seizure, 6 patients (9%) had rare seizures, 12 patients (19%) had a worthwhile improvement, and 21 patients (33%) failed to respond to surgery. Predictors of seizure-free outcome were age at seizure onset >15 years (p = 0.01), duration of epilepsy < or =5 years at the time of initial surgery (p = 0.03), and focal interictal discharges in scalp EEG (p = 0.03). Using a logistic regression model, two significant predictors emerged: duration of epilepsy < or =5 years (odds ratio, 3.18; p = 0.04) and preoperative focal interictal discharge (odds ratio, 4.45; p = 0.02). Complications of reoperation included visual field deficits (n = 9), wound infection (n = 2), subdural hematoma (n = 1), and hemiparesis (n = 1). CONCLUSION: Reoperation may be an appropriate alternative form of treatment for selected patients with intractable partial epilepsy who fail to respond to initial surgery.

Peri-ictal SPECT and surgical treatment for intractable epilepsy related to schizencephaly.

The authors evaluated four patients with schizencephaly who underwent subtraction ictal SPECT coregistered to MRI (SISCOM) prior to epilepsy surgery. Three patients had a SISCOM alteration that was concordant with the epileptic brain tissue. Two of these patients were rendered seizure-free and one individual experienced a significant reduction in seizures. The patient with an indeterminate SISCOM had an unfavorable outcome. SISCOM is useful in evaluating patients with schizencephaly for epilepsy surgery.

Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations.

OBJECTIVES: To determine the effect of stereotactic radiosurgery on seizure outcomes for patients with intracerebral arteriovenous malformations (AVM). METHODS: Between May 1990 and December 1998, 65 patients with a history of single or recurrent seizures underwent AVM radiosurgery, had more than 1 year of follow-up, and sufficient data to record an Engel seizure frequency score. The authors reviewed their records and updated clinical information when necessary with direct patient contact. Follow-up ranged from 12 to 144 months (median, 48 months). Seizure frequency was compared before and after radiosurgery with the Engel Seizure Frequency Scoring System. RESULTS: Overall, 26 patients (51%) were seizure-free (aura-free) after radiosurgery at 3-year follow-up; 40 patients (78%) had an excellent outcome (non-disabling simple partial seizures only) at 3-year follow-up. Factors associated with seizure-free or excellent outcomes include a low seizure frequency score (<4) before radiosurgery and smaller size and diameter AVM. Twenty-three patients had intractable partial epilepsy prior to treatment. Twelve (52%) of 23 and 11 of 18 (61%) patients with medically intractable partial epilepsy had excellent outcomes at years 1 and 3. CONCLUSION: Overall, stereotactic radiosurgery improves seizure outcomes in the majority of patients and more than half of the patients with medically intractable partial epilepsy had an excellent seizure outcome after radiosurgery.

Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation.

BACKGROUND: Syndromes of bilateral symmetric polymicrogyria include an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), in which the malformation is most severe rostrally. The authors describe a new syndrome they have termed "bilateral generalized polymicrogyria" (BGP), in which the malformation occurs in a generalized distribution but is often most severe in the perisylvian regions. METHODS: Patients with bilateral polymicrogyria were identified from multiple medical centers worldwide. The diagnosis of BGP was based on findings from conventional spin echo MRI and, in one case, postmortem neuropathologic findings. Genetic analysis was performed for those patients from consanguineous pedigrees and those with multiple affected siblings to rule out linkage to the BFPP locus on chromosome 16q. RESULTS: Twelve patients were identified with BGP. Clinical features included cognitive and motor delay as well as seizures. Some specific features characteristic of other known bilateral polymicrogyria syndromes, such as pseudobulbar palsy and dysconjugate gaze, were not commonly seen in these patients. Radiologically, polymicrogyria appeared widespread but was often most severe in the perisylvian regions. Pathologic examination in one case revealed a diffusely thin and excessively folded cerebral cortex lacking normal six-layered architecture. Seven patients subjected to genetic analysis did not demonstrate linkage to the BFPP locus. CONCLUSIONS: BGP is a distinct syndrome of cortical malformation. Several features allow BGP to be distinguished from other disorders on the growing list of bilateral symmetric polymicrogyria syndromes.

Cardiac troponin levels following monitored epileptic seizures.

Cardiac arrhythmia associated with myocardial injury is a proposed mechanism for sudden unexplained death in epilepsy. The authors measured serial cardiac troponin levels in 11 patients after monitored seizures. Using highly sensitive assays and criteria, no troponin elevations were seen, indicating that myocardial injury does not occur during uncomplicated seizures. An elevation in postictal troponin elevations should suggest the presence of cardiac injury secondary to neurocardiogenic mechanisms or primary cardiac factors, prompting further evaluation.

Comparative diagnostic utility of 1H MRS and DWI in evaluation of temporal lobe epilepsy.

OBJECTIVE: To compare the ability of diffusion-weighted MRI (DWI) and (1)H MRS to lateralize to the temporal lobe of seizure onset and to predict postoperative seizure control in patients with temporal lobe epilepsy (TLE). METHODS: Forty TLE patients who subsequently underwent epilepsy surgery and 20 normal subjects were studied with (1)H MRS and DWI. Medial parietal and temporal lobe N-acetylaspartate (NAA)/creatine (Cr) ratios and hippocampal and temporal stem apparent diffusion coefficients (ADC) were obtained. Lateralization to either temporal lobe with each MR measurement was based on the threshold values derived from +/-1-SD right/left ratios of normal subjects. RESULTS: Temporal lobe NAA/Cr lateralized to the operated temporal lobe in 18 of 40 (45%), hippocampal ADC in 32 of 40 (80%), and temporal stem ADC in 26 of 40 (65%) patients. Almost all of the cases that lateralized to the surgical side with NAA/Cr ratios (94%) had an excellent postoperative seizure control (p = 0.01). Lateralization to the side of surgery was not associated with surgical outcome with hippocampal and temporal stem ADC (p > 0.05). CONCLUSION: (1)H MRS and DWI complement each other in the clinical setting. DWI more frequently lateralized to the operated side, and (1)HMRS was a better predictor of postoperative seizure control.

Long-term mortality after a first episode of status epilepticus.

OBJECTIVE: To evaluate long-term mortality among people with status epilepticus (SE). METHODS: The authors performed a population-based retrospective cohort study to determine long-term mortality after SE. Between January 1, 1965, and December 31, 1984, all first episodes of SE receiving medical attention were ascertained through the Rochester Epidemiology Project Records-Linkage System. Cases surviving the first 30 days (n = 145) were followed until death or study termination (February 1996). RESULTS: At 10 years, cumulative mortality among 30-day survivors was 43%. The standardized mortality ratio (SMR) at 10 years was 2.8 (95% CI, 2.1-3.5). The mortality rate of those with idiopathic/cryptogenic SE was not increased (SMR = 1.1; 95% CI, 0.5-2.3). The following characteristics of SE increased long-term risk for mortality: SE > or = 24 hours in duration vs. SE < 2 hours (relative risk [RR] = 2.3; 95% CI, 1.1-5.1); acute symptomatic etiology vs idiopathic/cryptogenic etiology (RR = 2.2; 95% CI, 1.0-5.1) SE; myoclonic SE vs generalized convulsive SE (RR = 4.0; 95% CI, 1.3-13). CONCLUSION: Forty percent of subjects who survived the first 30 days after an incident episode of SE die within the next 10 years. The long-term mortality rate was threefold that of the general population over the same time period. The long-term mortality rate at 10 years was worse for those with myoclonic SE, for those who presented with SE lasting more than 24 hours, and for those with acute symptomatic SE. The long-term mortality rate was not altered in those with idiopathic/cryptogenic SE. We conclude that SE alone does not modify long-term mortality.

The effects of remifentanil on epileptiform discharges during intraoperative electrocorticography in patients undergoing epilepsy surgery.

PURPOSE: High-dose i.v. opioids (e.g., alfentanil, 50 microg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra-short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES. METHODS: After Institutional Review Board approval, 25 adult patients undergoing elective ECoG-guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane < or =0.1% (end-tidal) in 50% N2O, and i.v. fentanyl, 2 microg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 microg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one-sided sign test; p values < or =0.05 were considered statistically significant. RESULTS: When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain. CONCLUSIONS: During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half-life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG-guided ES.

Seizures in patients with multiple sclerosis seen at Mayo Clinic, Rochester, Minn, 1990-1998.

OBJECTIVE: To evaluate seizure type, electroencephalographic findings, and response to antiepileptic drug (AED) treatment in patients with multiple sclerosis (MS) and coexistent seizure activity. PATIENTS AND METHODS: We reviewed the medical records of all patients seen at the Mayo Clinic in Rochester, Minn, with the diagnosis of MS and seizures between 1990 and 1998. RESULTS: During the study period, 5715 patients with MS were identified. Of these 5715 patients, 51 (0.89%) experienced seizure activity. The most common ictal behavior was a generalized tonic-clonic seizure in 35 patients (68.6%). Simple or complex partial seizures occurred in 11 patients (21.6%), and 18 patients (35.3%) had only 1 seizure episode. Focal motor status epilepticus, ie, epilepsia partialis continua, occurred in 3 patients (5.9%) and was associated with cognitive impairment. In 37 patients (72.5%), the initial seizure presentation was after the diagnosis of MS. A seizure resulted in the diagnosis of MS or occurred before the diagnosis of MS but after other symptoms or signs of demyelinating disease in 14 patients (27.4%). Electroencephalography was performed in 43 patients. Electroencephalographic findings included diffuse or localized nonspecific background slowing in 19 patients (44.2%), unilateral or bilateral frontotemporal spike discharges in 9 (20.9%), generalized atypical spike-and-wave or multifocal independent epileptiform alterations in 6 (14.0%), and normal results in 11 (25.6%). Of the 45 patients who received AED therapy, 35 (77.8%) had an excellent response, ie, they were seizure free. Five treated patients (11.1%) had an intractable seizure disorder. CONCLUSION: Most of the patients with MS who experienced seizure activity had a benign and transient disorder that was responsive to AED treatment or required no therapy.

The relationship between quantitative T2 relaxometry and memory in nonlesional temporal lobe epilepsy.

PURPOSE: We investigated the relationship between preoperative quantitative magnetic resonance imaging (MRI) T2 relaxometry and volumetry of the hippocampi and pre- and postoperative verbal memory in temporal lobectomy patients who had nonlesional temporal lobe epilepsy. METHODS: Pre- and postoperative memory data based on the Logical Memory (LM) subtest of the Wechsler Memory Scale-Revised (WMS-R) and the 30-min delayed recall trial of the Rey Auditory Verbal Learning Test (AVLT) were obtained from 26 left and 15 right temporal lobectomy patients. Coronal MRI T2 maps were generated for these 41 temporal lobectomy patients as well as 61 control patients. Hippocampal T2 relaxation times and hippocampal volumes, converted to z scores using control group data, were correlated with neuropsychological performance in the patients. RESULTS: In left temporal lobe-onset patients, high T2 in the left hippocampal body predicted higher LM performance after surgery. Asymmetrically high T2 in the left hippocampal body (i.e., the right-minus-left difference), compared with the right hippocampal body, also predicted higher LM performance after surgery. In right temporal lobe-onset patients, high T2 in the left hippocampal body predicted relatively lower AVLT performance after surgery. Multiple regression analysis in left temporal-onset patients revealed that high T2 in the left hippocampal body together with higher preoperative LM performance predict higher postoperative LM performance. CONCLUSIONS: Our findings suggest that elevated (i.e., abnormal) hippocampal T2 signal is associated with memory ability (or hippocampal functional capacity) independent of MRI-determined hippocampal atrophy. Therefore, our findings support the use of quantitative T2 relaxometry as an independent predictor of verbal memory outcome in both left and right TLE patients who are candidates for temporal lobectomy.

Video-EEG monitoring in patients with hippocampal atrophy.

OBJECTIVES: To analyze the value of ictal EEG recordings in patients with unilateral magnetic resonance imaging (MRI)-identified hippocampal atrophy and concordant interictal epileptiform discharges (IEDs). MATERIAL AND METHODS: The ictal EEG patterns in 84 patients with pharmaco resistant epilepsy undergoing an anterior temporal lobectomy between 1992 and 1995 were reviewed. The concordance between the ictal EEG and MRI and the IEDs was examined. RESULTS: Two-hundred-and-thirty seizures (76.4%) were concordant and 11 seizures (3.7%) were discordant with the atrophic temporal lobe. Sixty seizures (19.9%) were indeterminate in localization. Sixty-three of the 69 patients (91.3%) with confirmatory and 14 of the 15 patients (93%) with non-confirmatory ictal EEG recordings, respectively, experienced an excellent operative outcome (P=0.629, Fisher's exact test). CONCLUSIONS: Patients with unilateral hippocampal atrophy and concordant IEDs are excellent surgical candidates even when video-EEG monitoring shows discordant or non-localizing seizures.

Use of routine and video electroencephalography.

The routine EEG continues to be a pivotal diagnostic study in the evaluation of patients with suspected seizure disorders. The identification of potentially epileptiform alterations is important in the classification of the epilepsy and in determining the presence of an epileptic syndrome. The electroclinical correlation observed during long-term EEG monitoring may be used for diagnostic classification and surgical localization. Confirmation of a seizure disorder may be a priority before initiating antiepileptic drug therapy in selected patients. Finally, recognition of the ictal EEG pattern is necessary in evaluating patients with intractable seizure disorders for surgical treatment.

Incidence and risk factors in sudden unexpected death in epilepsy: a prospective cohort study.

OBJECTIVE: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP). METHODS: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center. RESULTS: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP. CONCLUSIONS: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.