Thaddeus S. Walczak

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.

Predicting long-term seizure outcome after resective epilepsy surgery The Multicenter Study

Background: In a seven-center prospective observational study of resective epilepsy surgery, the authors examined probability and predictors of entering 2-year remission and the risk of subsequent relapse. Methods: Patients aged 12 years and over were enrolled at time of referral for epilepsy surgery, and underwent standardized evaluation, treatment, and follow-up procedures. The authors defined seizure remission as 2 years completely seizure-free after hospital discharge with or without auras, and relapse as any seizures after 2-year remission. The authors examined type of surgery, seizure, clinical and demographic variables, and localization study results with respect to prediction of seizure remission or relapse, using χ2 and proportional hazards analysis. Results: Of 396 operated patients, 339 were followed over 2 years, and 223 (66%) experienced 2-year remission, not significantly different between medial temporal (68%) and neocortical (50%) resections. In multivariable models, only absence of generalized tonic-clonic seizures and presence of hippocampal atrophy were significantly and independently associated with remission, and only in the medial temporal resection group. Fifty-five patients relapsed after 2-year remission, again not significantly different between medial temporal (25%) and neocortical (19%) resections. Only delay to remission predicted relapse, and only in medial temporal patients. Conclusion: Hippocampal atrophy and a history of absence of generalized tonic clonic seizures were the sole predictors of 2-year remission, and only for medial temporal resections.

Distribution of partial seizures during the sleep–wake cycle Differences by seizure onset site

Objective: To evaluate the effects of sleep on partial seizures arising from various brain regions. Methods: The authors prospectively studied 133 patients with localization-related epilepsy undergoing video-EEG monitoring over a 2-year period. Seizure type, site of onset, sleep/wake state at onset, duration, and epilepsy syndrome diagnosis were recorded. Periorbital, chin EMG, and scalp/sphenoidal electrodes were used. A subset of 34 patients underwent all-night polysomnography with scoring of sleep stages. Results: The authors analyzed 613 seizures in 133 patients. Forty-three percent (264 of 613) of all partial seizures began during sleep. Sleep seizures began during stages 1 (23%) and 2 (68%) but were rare in slow-wave sleep; no seizures occurred during REM sleep. Temporal lobe complex partial seizures were more likely to secondarily generalize during sleep (31%) than during wakefulness (15%), but frontal lobe seizures were less likely to secondarily generalize during sleep (10% versus 26%; p < 0.005). Conclusions: Partial-onset seizures occur frequently during NREM sleep, especially stage 2 sleep. Frontal lobe seizures are most likely to occur during sleep. Patients with temporal lobe seizures have intermediate sleep seizure rates, and patients with seizures arising from the occipital or parietal lobes have rare sleep-onset seizures. Sleep, particularly stage 2 sleep, promotes secondary generalization of temporal and occipitoparietal, but not frontal, seizures. These findings suggest that the hypersynchrony of sleep facilitates both initiation and propagation of partial seizures, and that effects of sleep depend in part on the location of the epileptic focus.

Effects of Sleep and Sleep Stage on Epileptic and Nonepileptic Seizures

Summary: Purpose: Previous studies of patients with epilepsy and animal models of epilepsy suggest that sleep increases the frequency, duration, and secondary generalization of seizures. This information is, however, incomplete.

Combined analysis of risk factors for SUDEP

Purpose:  To pool data from four published case–control studies of sudden unexpected death in epilepsy (SUDEP) with live controls, to increase the power to determine risk factors.

How long does it take for partial epilepsy to become intractable

Background: Much remains unknown about the natural history of intractable localization-related epilepsy, including how long it typically takes before intractability becomes evident. This information could guide the design of future studies, resolve certain discrepancies in the literature, and provide more accurate information about long-term prognosis. Methods: Individuals evaluated for resective surgery for refractory localization-related epilepsy were prospectively identified at the time of initial surgical evaluation at seven surgical centers (between 1996 and 2001). The latency time between onset of epilepsy and failure of second medication and history of remission (≥1 year seizure-free) before surgical evaluation were examined with respect to age at onset, hippocampal atrophy, febrile seizures, and surgical site. Results: In the 333 patients included in the analysis, latency time was 9.1 years (range 0 to 48) and 26% reported a prior remission before surgery. A prior remission of ≥5 years was reported by 8.5% of study participants. Younger age at onset was strongly associated with longer latency time (p < 0.0001) and higher probability of past remission (p < 0.0001). In multivariable analyses, age at onset remained as the most important explanatory variable of both latency time and prior remission. Conclusions: A substantial proportion of localization-related epilepsy may not become clearly intractable for many years after onset. This is especially true of epilepsy of childhood and early adolescent onset. If prospective studies confirm these findings and the underlying mechanisms behind these associations become understood, this raises the possibility of considering interventions that might interrupt such a process and some day prevent some forms of epilepsy from becoming intractable.

Initial outcomes in the Multicenter Study of Epilepsy Surgery

Objective: To obtain prospective data regarding seizures, anxiety, depression, and quality of life (QOL) outcomes after resective epilepsy surgery. Methods: The authors characterized resective epilepsy surgery patients prospectively at yearly intervals for seizure outcome, QOL, anxiety, and depression, using standardized instruments and patient interviews. Results: Of 396 patients who underwent resective surgical procedures, 355 were followed for at least 1 year. Of these, 75% achieved a 1-year remission at some time during follow-up; patients with medial temporal (77%) were more likely than neocortical resections (56%) to achieve remission (p = 0.01). Relapse occurred in 59 (22%) patients who remitted, more often in medial temporal (24%) than neocortical (4%) resected patients (p = 0.02). QOL, anxiety, and depression all improved dramatically within 3 months after surgery (p < 0.0001), with no significant difference based on seizure outcome. After 3 months, QOL in seizure-free patients further improved gradually, and patients with seizures showed gradual declines. By 12 and 24 months, overall QOL and its epilepsy-targeted and physical health domains were significantly different in the two outcome groups. (Anxiety and depression scores also gradually diverged, with improvements in seizure-free and declines in continued seizure groups, but differences were not significant.) Conclusion: Resective surgery for treatment of epilepsy significantly reduces seizures, most strikingly after medial temporal resection (77% 1 year remission) compared to neocortical resection (56% 1 year remission). Resective epilepsy surgery has a gradual but lasting effect on QOL, but minimal effects on anxiety and depression. Longer follow-up will be essential to determine ultimate seizure, QOL, and psychiatric outcomes of epilepsy surgery.

Changes in depression and anxiety after resective surgery for epilepsy

Objective: To determine changes in depression and anxiety after resective surgery. Methods: Data from subjects enrolled in a prospective multicenter study of resective epilepsy surgery were reviewed with the Beck Psychiatric Symptoms Scales (Beck Depression Inventory [BDI] and Beck Anxiety Inventory [BAI]) and Composite International Diagnostic Interview (CIDI) up to a 24-month period. χ2 analyses were used to correlate proportions. Results: A total of 358 presurgical BDI and 360 BAI results were reviewed. Moderate and severe levels of depression were reported in 22.1% of patients, and similar levels of anxiety were reported by 24.7%. Postoperative rates of depression and anxiety declined at the 3-, 12-, and 24-month follow-up periods. At the 24-month follow-up, moderate to severe levels of depression symptoms were reported in 17.6 and 14.7% of the patients who continued to have postoperative seizures. Moderate to severe depression and anxiety were found in 8.2% of those who were seizure-free. There was no relationship, prior to surgery, between the presence or absence of depression and anxiety and the laterality or location of the seizure onset. There were no significant relationships between depression or anxiety at 24-month follow-up and the laterality or location of the surgery. Conclusions: Depression and anxiety in patients with refractory epilepsy significantly improve after epilepsy surgery, especially in those who are seizure-free. Neither the lateralization nor the localization of the seizure focus or surgery was associated with the risk of affective symptoms at baseline or after surgery.

The Multicenter Study of Epilepsy Surgery : Recruitment and Selection for Surgery

Summary:  Purpose: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single‐center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries.

Outcome After Diagnosis of Psychogenic Nonepileptic Seizures

Summary: Information regarding outcome in patients with psychogenic nonepileptic seizures (PNES) is limited. We attempted to contact 72 consecutive patients with PNES confirmed by video‐EEG monitoring: 51 of 72 (71%) were reached a mean of 15 months (range 12–27 months) after diagnosis and agreed to answer a structured telephone questionnaire. The questionnaire assessed the number of PNES in the last 6 months, antiepileptic drug (AED) use, occupational status, global self‐rating, and extent of psychotherapeutic treatments. PNES had ceased in 18 of 51 (35%), decreased >80% in 21 of 51 (41%), and decreased <80% in 12 of 51 (24%). Thirtythree of 51 (65%) were not taking AEDs. Occupational stotus improved in 20% and did not change in 75%. Overall, 29 of 51 (57%) rated themselves markedly improved and 15 of 51 (29%) rated themselves unchanged or worse. Persisting PNES were associated with longer duration of PNES before diagnosis (p < 0.02) and presence of additional psychiatric disease (p < 0.01). Persisting PNES were not associated with gender, presence of epileptic seizures, or extent of psychotherapeutic treatments after diagnosis. Placebo saline infusion had been administered in some patients to help precipitate PNES. This did not affect the number of psychotherapy visits or outcome. We conclude that PNES cease or significantly decrease in most patients, but occupational status does not improve as often. Earlier diagnosis may improve outcome.