Steven V. Pacia

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.

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.

Localization of Temporal Lobe Foci by Ictal EEG Patterns

Identifying patients whose complex partial seizures originate in temporal neocortex rather than in hippocampus is important because such patients have less favorable outcomes with standard anteromesial temporal resections. We reviewed scalp‐recorded ictal EEGs of 93 epilepsy surgery candidates who either underwent intracranial EEG monitoring (n= 58) or who were referred directly for temporal lobectomy (n= 35). We defined seven patterns of early seizure discharges, grouped patients according to their seizure pattern, and correlated these with the site of seizure onset determined by intracranial EEG. Categorization by seizure pattern was also compared with brain magnetic resonance imaging (MRI) findings and intracarotid amobarbital (Wada) testing. An initial, regular 5‐ to 9‐Hz inferotemporal rhythm (type 1A) was most specific for hippocampal‐onset seizures. Less commonly, a similar vertex/parasagittal positive rhythm (type 1B) or a combination of types 1B and 1A rhythms (type 1C) was recorded. Seizures originating in temporal neocortex were most often associated with irregular, polymorphic, 2‐ to 5‐Hz lateralized activity (type 2A). This pattern was commonly followed by a type 1A theta rhythm (type 2B) or was preceded by repetitive, sometimes periodic, sharp waves (type 2C). Seizures without a clear lateralized EEG discharge (type 3) were most commonly of temporal neocortical origin. These associations between type of seizure pattern and probable site of cerebral origin were statistically significant. MRI and Wada testing did not have as much specificity as ictal patterns in differentiating among seizure origins. We conclude that the initial pattern of ictal discharge on scalp EEG can assist in distinguishing seizures of temporal neocortical onset from those of hippocampal onset. This information can be used to identify patients for invasive monitoring.

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.

Intracranial EEG substrates of scalp ictal patterns from temporal lobe foci

Summary: Purpose: To determine the intracranial EEG features responsible for producing the various ictal scalp rhythms, which we previously identified in a new EEG classification for temporal lobe seizures.

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.

Clozapine‐related seizures Experience with 5,629 patients

We reviewed the incidence, clinical features, and management of all clozapine-related seizures in 5,629 patients monitored by the Clozaril Patient Management System, during the first 6 months after marketing. Seventy-one patients had generalized tonic-clonic seizures yielding a frequency of 1.3%. One patient had myoclonic seizures prior to generalization. Seizures tended to occur at low doses (< 300 mg/d) during the titration phase, and at high doses (≥ 600 mg/d) during the maintenance phase. Patients with a history of seizures or epilepsy were more likely to have seizures soon after initiation of therapy, on low doses. Twenty-nine of 37 patients (78%) who had seizures and were rechallenged with clozapine were able to continue the medication with dose reduction and more-gradual dose titration, or with the addition of an antiepileptic medication.

Relationships Between Seizure Severity and Health‐Related Quality of Life in Refractory Localization‐Related Epilepsy

Summary: Purpose: To evaluate relationships between self‐report measures of seizure severity and health‐related quality of life (HRQOL) in people with refractory localization‐related epilepsy.

Bradycardia and asystole induced by partial seizures A case report and literature review

Article abstract Bradyarrhythmias associated with partial seizures are uncommon, with most reported patients having temporal lobe seizure foci on scalp EEG recordings. We report a patient with bradycardia and sinus arrest during a complex partial seizure documented during bilateral subdural EEG and EEG and simultaneous video and EEG recordings. The seizure began in the left temporal lobe and spread to the right temporal region, with bradycardia occurring 55 seconds after ictal onset and asystole after 60 seconds.