Influence of head trauma on outcome following anterior temporal lobectomy.

BACKGROUND: There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy. Some of the existing studies may be biased because of patient selection and limitations in determining predisposition. OBJECTIVE: To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy. PATIENTS AND METHODS: We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were determined prospectively on at least 3 occasions before anterior temporal lobectomy. Risk factors investigated were a history of febrile convulsions, family history of epilepsy, significant head trauma, history of meningitis, history of encephalitis, or significant perinatal insult. Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings (hippocampus and lesion). Outcome was determined using Engel's classification. For statistical analysis we used successive logistic regression analysis, chi(2) test, Fisher exact test, and t test. RESULTS: Of the 102 patients, 13 had no identified risk factor for epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22 with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2 history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult. Seventy-one (70%) were classified as Engel's class I, with 56 patients continuously free of seizures at follow-up. Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor (P = .27). No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy, but the presence of head trauma, alone or in combination, was correlated with continued seizures following anterior temporal lobectomy (P = .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma before the age of 5 years (P = .57). These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis. Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others (P = .82). CONCLUSIONS: Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy. No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures. This information may be used in preoperative counseling of patients.

Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease.

We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa. Dose response to ramped intravenous levodopa infusion was measured after overnight drug withdrawal on two occasions: first after chronic, intermittent oral levodopa/carbidopa, and second after 3 to 5 days of continuous intravenous levodopa. Continuous intravenous levodopa shifted the dyskinesia dose-response curve to the right, reduced maximum dyskinesia activity, but did not significantly alter dose response for relief of parkinsonism. Improvement in dyskinesia was apparent by the second day of continuous levodopa, during which ratios of plasma dopa/3-O-methyldopa remained constant. Our results support the hypothesis that relief of parkinsonism and production of dyskinesia by levodopa occur by separate mechanisms.

Increased secondary generalization of partial seizures after temporal lobectomy.

OBJECTIVE: This study tests the primary hypothesis that secondary generalization of partial seizures is more likely after anterior temporal lobectomy (ATL) than before ATL, and the secondary hypothesis that antiepileptic drug withdrawal accounts for increased generalization of seizures postoperatively. BACKGROUND: The authors observed that some patients had generalized tonic-clonic (GTC) seizures after but not before ATL, by using a new classification of outcome that compares preoperative and postoperative seizure frequencies by seizure type. METHODS: Twenty patients with refractory temporal lobe epilepsy had postoperative GTC seizures or nongeneralizing complex partial (CP) seizures in a consecutive ATL series. All had reduced seizure frequency postoperatively and more than 2 years of follow-up on antiepileptic drugs. The authors calculated a generalization fraction, as (number of GTC seizures)/(number of CP and GTC seizures), for 2 years before and 2 years after surgery. RESULTS: Postoperative generalization fractions were greater than preoperative generalization fractions (Wilcoxon signed-rank test, p < 0.01). Most postoperative GTC seizures were not associated with antiepileptic drug withdrawal, and postoperative GTC seizures were not more associated with drug withdrawal than were postoperative CP seizures. Patients with more than two GTC seizures per year preoperatively were more likely than other patients to have postoperative GTC seizures. CONCLUSIONS: Patients with reduced seizure frequency after ATL have a greater tendency for partial seizures to secondarily generalize postoperatively. This phenomenon is not explained by antiepileptic drug withdrawal.

Suppression of dyskinesias in advanced Parkinson's disease. II. Increasing daily clozapine doses suppress dyskinesias and improve parkinsonism symptoms.

We gave increasing daily doses of clozapine to six patients with advanced Parkinson's disease (PD) and levodopa-induced dyskinesias. Clozapine reduced the daily dyskinesia time five-fold, increased "on" time eight-fold, and doubled the serum [DOPA] producing half-maximal dyskinesia. Parkinsonism scores after overnight DOPA withdrawal improved with increasing daily clozapine intake, and there was no clozapine dose-related shift in levodopa dose response for relief of parkinsonism. Patients experienced sedation, sialorrhea, and orthostatic hypotension. Clozapine appears to be an effective agent for suppression of levodopa-induced dyskinesias in PD.

Spatiotemporal patterns of beta desynchronization and gamma synchronization in corticographic data during self-paced movement.

OBJECTIVE: To study the spatiotemporal pattern of event-related desynchronization (ERD) and event-related synchronization (ERS) in electrocorticographic (ECoG) data with closely spaced electrodes. METHODS: Four patients with epilepsy performed self-paced hand movements. The ERD/ERS was quantified and displayed in the form of time-frequency maps. RESULTS: In all subjects, a significant beta ERD with embedded gamma ERS was found. CONCLUSIONS: Self-paced movement is accompanied not only by a relatively widespread mu and beta ERD, but also by a more focused gamma ERS in the 60-90 Hz frequency band.

Indications and outcome of ictal recording with intracerebral and subdural electrodes in refractory complex partial seizures.

Intracranial electrophysiologic recording has often been used to localize ictal onset zones in presurgical evaluation of refractory complex partial seizures. Specific indications for intracranial ictal monitoring have not been analyzed in detail, however. The authors designed this study to test the utility of intracranial monitoring in specific indications and considered six specific indications for intracranial monitoring. They compared prospectively determined indications and outcomes of chronic intracerebral and subdural electrophysiologic recording in 50 consecutive patients whose ictal onset zones had been inadequately localized with interictal and ictal EEG using extracranial electrodes, magnetic resonance imaging, interictal[18F]fluorodeoxyglucose positron emission tomography, and neuropsychological testing. In 47 patients ictal onset zones were localized with intracranial recordings, leading to resections in 38 patients. Each indication for intracranial monitoring selected a group in which the majority went on to have efficacious epilepsy surgery (5-year follow-up). Definitive diagnosis of bilateral independent ictal onset zones in temporal lobe epilepsy required intracranial ictal EEG. Intracranial EEG localization supported efficacious resection in most patients, despite contradictory or nonlocalizing extracranial ictal EEG and neuroimaging abnormalities. Critical analysis of these specific indications for intracranial monitoring may be useful in multicenter evaluation of these techniques.

Identification of electrocorticogram patterns as the basis for a direct brain interface.

This study reports on the first step in the development of a direct brain interface based on the identification of event-related potentials (ERPs) from an electrocorticogram obtained from the surface of the cortex. Ten epilepsy surgery patients, undergoing monitoring with subdural electrode strips and grid arrays, participated in this study. Electrocorticograms were continuously recorded while subjects performed multiple repetitions for each of several motor actions. ERP templates were identified from action-triggered electrocorticogram averages using an amplitude criterion. At least one ERP template was identified for all 10 subjects and in 56% of all electrode-recording sets resulting from a subject performing an action. These results were obtained with electrodes placed solely for clinical purposes and not for research needs. Eighty-two percent of the identified ERPs began before the trigger, indicating the presence of premovement ERP components. The regions yielding the highest probability of valid ERP identification were the sensorimotor cortex (precentral and postcentral gyri) and anterior frontal lobe, although a number were recorded from other areas as well. The recording locations for multiple ERPs arising from the performance of a specific action were usually found on close-by electrodes. ERPs associated with different actions were occasionally identified from the same recording site but often had noticeably different characteristics. The results of this study support the use of ERPs recorded from the cortical surface as a basis for a direct brain interface.

Detection of event-related potentials for development of a direct brain interface.

The study presented here is part of an ongoing effort to develop a direct brain interface based on detection of event-related potentials (ERPs). In a study presented in a companion article, averaged ERP templates were identified from electrocorticograms recorded during repetition of voluntary motor actions. Here the authors report on the detection of individual motor ERPs within the electrocorticogram using cross-correlation. An averaged ERP template was created from the first half of each electrocorticogram and then cross-correlated with the continuous electrocorticogram from the second half. Points where the cross-correlation value exceeded an experimentally determined detection threshold were considered to be detection points. A detection point was considered to be a valid "hit" if it occurred between 1 second before and 0.25 second after the recorded time of a voluntary action. The difference between the hit and false-positive percentages (HF-difference) was used as a metric of detection accuracy. HF-differences greater than 90 were found for 5 of 15 subjects, HF-differences greater than 75 were found for 8 of 15 subjects, and HF-differences greater than 50 were found for 12 of 15 subjects. The three other subjects with HF-differences less than 50 had electrode locations not well suited for recording movement-related ERPs. Recordings from sensorimotor and supplementary motor areas produced the highest yield of channels with HF-difference greater than 50; however, a number of channels with good performance were found in other areas as well. The results demonstrate the likely prospect of using ERP detection as the basis of a single-switch direct brain interface and that furthermore, there is a good possibility of obtaining multiple control channels using this approach.

A randomized trial of decision-making in asymptomatic carotid stenosis.

OBJECTIVE: We sought to evaluate whether different presentation formats, presenter characteristics, and patient characteristics affect decision-making in asymptomatic carotid stenosis. METHODS: Subjects included individuals presenting to a neurology clinic. Participants included those over age 18 without known carotid stenosis. Subjects were randomized to a 30-second video with 1 of 5 presentation formats (absolute risk, absolute event-free survival, annualized absolute risk, relative risk, and a qualitative description) delivered by 1 of 4 presenter physicians (black woman, white woman, black man, white man). Subjects then completed a one-page form regarding background demographics and their decision regarding treatment choice. RESULTS: A total of 409 subjects watched the video and completed the survey. Overall, 48.4% of subjects chose surgery. Presentation format strongly predicted choice of surgery (qualitative [64%], relative risk [63%], absolute risk [43%], absolute event-free survival [37%], and annualized absolute risk [35%], p < 0.001). There was a trend for younger age (mean age 52 vs 55, p = 0.054), male gender (53% vs 45%, p = 0.08), and advanced education (42% for high school education or less vs 52% for more than high school education, p = 0.052) to predict surgery choice. Gender and race of presenter, and race of subject, had no influence on the choice of treatment. CONCLUSIONS: Presentation format (information framing) strongly determines patient decision-making in asymptomatic carotid stenosis. Subject age, gender, and education level may also influence the decision. Clinicians should consider the influence of these variables when counseling patients.

Pilot trial of IOM duty hour recommendations in neurology residency programs: unintended consequences.

OBJECTIVE: To study the potential effect of the 2008 Institute of Medicine (IOM) work duty hour (WDH) recommendations on neurology residency programs. METHODS: This study evaluated resident sleepiness, personal study hours, quality of life, and satisfaction and faculty satisfaction during a control month using the Accreditation Council for Graduate Medical Education WDH requirements and during an intervention month using the IOM WDH recommendations. Resident participation in both schedules was mandatory, but both resident and faculty participation in the outcome measures was voluntary. RESULTS: Thirty-four residents (11 postgraduate year [PGY]-4, 9 PGY-3, and 14 PGY-2) participated. End-of-work shift sleepiness, mean weekly sleep hours, personal study hours, and hours spent in lectures did not differ between the control and intervention months. Resident quality of life measured by the Maslach Burnout Inventory declined for 1 subscore in the intervention month (p = 0.03). Resident education satisfaction declined during the intervention month for issues related to continuity of care, patient hand-offs, and knowledge of their patients. Faculty satisfaction declined during the intervention month, without a decline in quality of life. CONCLUSIONS: The results from 3 residency programs suggest that the IOM WDH recommendations may negatively affect neurology resident education. This study was limited by the short duration of implementation, negative bias against the IOM recommendations, and inability to blind faculty. Additional study of the IOM WDH recommendations is warranted before widespread implementation.

Education research: neurology residency training in the new millennium.

OBJECTIVE: To survey adult neurology program directors (ANPD) to identify their most pressing needs at a time of dramatic change in neurology resident education. METHODS: All US ANPD were surveyed in 2007 using an instrument adjusted from a 1999 survey instrument. The goal was to characterize current program content, the institution and evaluation of the core competencies, program director characteristics, program director support, the institution of work duty hour requirements, resident support, and the curriculum needs of program directors and programs. RESULTS: A response rate of 82.9% was obtained. There is a significant disconnect between administration time spent by ANPD and departmental/institutional support of this, with ANPD spending approximately 35% of a 50-hour week on administration with only 16.7% salary support. Rearrangement of rotations or services has been the most common mode for ANPD to deal with work duty hour requirements, with few programs employing mid level providers. Most ANPD do not feel work duty hour reform has improved resident education. More residents are entering fellowships following graduation than documented in the past. Curriculum deficiencies still exist for ANPD to meet all Neurology Program Requirements, especially for nontraditional neurology topics outside the conventional bounds of clinical neurology (e.g., practice management). Nearly one quarter of neurology residency programs do not have a meeting or book fund for every resident in the program. CONCLUSIONS: Adult neurology program directors (ANPDs) face multiple important financial and organizational hurdles. At a time of increasing complexity in medical education, ANPDs need more institutional support.

Education research: Bias and poor interrater reliability in evaluating the neurology clinical skills examination.

OBJECTIVE: The American Board of Psychiatry and Neurology (ABPN) has recently replaced the traditional, centralized oral examination with the locally administered Neurology Clinical Skills Examination (NEX). The ABPN postulated the experience with the NEX would be similar to the Mini-Clinical Evaluation Exercise, a reliable and valid assessment tool. The reliability and validity of the NEX has not been established. METHODS: NEX encounters were videotaped at 4 neurology programs. Local faculty and ABPN examiners graded the encounters using 2 different evaluation forms: an ABPN form and one with a contracted rating scale. Some NEX encounters were purposely failed by residents. Cohen's kappa and intraclass correlation coefficients (ICC) were calculated for local vs ABPN examiners. RESULTS: Ninety-eight videotaped NEX encounters of 32 residents were evaluated by 20 local faculty evaluators and 18 ABPN examiners. The interrater reliability for a determination of pass vs fail for each encounter was poor (kappa 0.32; 95% confidence interval [CI] = 0.11, 0.53). ICC between local faculty and ABPN examiners for each performance rating on the ABPN NEX form was poor to moderate (ICC range 0.14-0.44), and did not improve with the contracted rating form (ICC range 0.09-0.36). ABPN examiners were more likely than local examiners to fail residents. CONCLUSIONS: There is poor interrater reliability between local faculty and American Board of Psychiatry and Neurology examiners. A bias was detected for favorable assessment locally, which is concerning for the validity of the examination. Further study is needed to assess whether training can improve interrater reliability and offset bias.

Suppression of dyskinesias in advanced Parkinson's disease: moderate daily clozapine doses provide long-term dyskinesia reduction.

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns. Clozapine exerts a dose-related suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.

Nonepileptic seizure outcome varies by type of spell and duration of illness.

PURPOSE: To determine whether differences in clinical manifestations of psychogenic nonepileptic events are associated with differences in outcome and whether the length of illness before diagnosis correlates with outcome. METHODS: We reviewed ictal videotapes and EEGs in 85 patients diagnosed with exclusively nonepileptic psychogenic seizures during inpatient CCTV-EEG monitoring at the University of Michigan between June 1994 and December 1996. They were classified into groups of similar ictal behaviors. Fifty-seven of these patients were available to respond to a follow-up telephone survey about their condition 2-4 years after discharge. We examined demographics, baseline EEG abnormalities, and outcome of treatment interventions. We also evaluated whether interventions were more likely to succeed if patients were diagnosed early in the course of the illness. RESULTS: We found that the largest groups consisted of patients with motionless unresponsiveness ("catatonic," n = 19) and asynchronous motor movements with impaired responsiveness ("thrashing," n = 19). Infrequent signs included tremor, automatisms, subjective events with amnesia, and intermittent behaviors. There was a higher incidence of baseline EEG abnormalities in the thrashing group (31%) than in the catatonic group (0%). There was a higher incidence of complete remission of spells in the catatonic group (53%) than in the thrashing group (21%). Patients who had a more recent onset of seizures (most often within 1 year) were much more likely to have remission of spells after diagnosis. CONCLUSIONS: Classification of nonepileptic seizures is useful in predicting outcome and may be valuable in further investigation of this complex set of disorders.

Ictal spiking patterns recorded from temporal depth electrodes predict good outcome after anterior temporal lobectomy.

PURPOSE: Investigators have shown that the presence of ictal spiking (IS) recorded from temporal depth electrodes is associated with mesial temporal sclerosis (MTS). We investigated the relation of IS to seizure control and pathology after anterior temporal lobectomy (ATL). METHODS: All patients undergoing intracranial ictal monitoring from a single institution since 1989 were identified. Those who did not undergo ATL or had postoperative follow-up of <1 year were excluded. All received at a minimum bilateral temporal depth electrodes. Ictal recordings were reviewed for the presence of IS, and the proportion of seizures with IS was determined for each patient. Outcome was determined by using Engel's classification. Surgical specimens were reviewed for pathology. Statistics used were chi2, Fisher exact test, and Wilcoxon rank sum. RESULTS: Forty patients with 571 seizures were reviewed. In 292 seizures from 32 patients, IS was seen. Outcomes were 24 class I (22 with IS), five class II (four with IS), three class III (one with IS), seven class IV (four with IS), and one lost to follow-up (with IS). Pathologic review revealed 25 with MTS, 22 of whom had IS. The presence of IS was associated with class I outcomes (p = 0.04), but not MTS (p = 0.06). Patients with class I outcomes had a significantly greater proportion of seizures with IS (mean, 0.58 +/- 0.3) compared with other outcomes (mean, 0.30 +/- 0.3, p = 0.02). CONCLUSIONS: The presence of IS and higher proportion of seizures with IS correlated with good seizure outcome after ATL. This information may be used in preoperative counseling.

Value of inpatient diagnostic CCTV-EEG monitoring in the elderly.

PURPOSE: To examine the outcome of inpatient diagnostic closed circuit TV-EEG (CCTV-EEG) monitoring in a consecutive series of elderly patients admitted to an adult epilepsy-monitoring unit (EMU) over a continuous 6-year period. METHODS: Retrospective review of all admissions to a university hospital adult EMU. Those older than 60 years were identified. Patients who were monitored for status epilepticus were excluded. Data on duration of events, frequency of events, physical examination, medications, preadmission EEG, brain imaging, length of stay, and interictal and ictal EEG were obtained. RESULTS: Of the 18 patients admitted for monitoring only, mean age was 69.5 years (range, 60-90 years). Mean length of stay was 4.3 days (range, 2-9 days). Five patients had complex partial seizures recorded. Three patients, all treated with anti-epileptic drugs (AEDs), had no spells recorded, and no additional diagnostic information was gained from the admission. The other 10 patients, eight of whom had been treated with AEDs, were symptomatic during their admission, leading to a variety of neurologic but not epileptic, psychiatric, or other medical disorders, and allowing tapering of AEDs. CONCLUSIONS: In elderly patients with suspected epilepsy, CCTV-EEG is a very useful diagnostic tool. In this series of 18, 10 patients were diagnosed with potentially treatable medical illnesses not responsive to AEDs.

A direct brain interface based on event-related potentials.

Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERP's. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.