Faculty Bibliography

We developed an instrument to measure health-related quality of life (HRQOL) in epilepsy. A 99-item inventory was constructed from the RAND 36-Item Health Survey (generic core), with 9 additional generic items, 48 epilepsy-targeted items, and 6 other items concerning attitudes toward epilepsy and self-esteem. We administered the 99-item inventory to 304 adults with epilepsy at 25 epilepsy centers. Patients and patient-designated proxies completed the inventory and were retested 1-91 days later. A multitrait scaling analysis of these data led to retention of 86 items distributed in 17 multiitem scales (Cronbach's alpha ranged from 0.78 to 0.92). Factor analysis of the 17 multiitem scales yielded four underlying dimensions of health: an epilepsy-targeted dimension, a cognitive factor, mental health, and physical health. Construct validity was supported by significant patient-proxy correlations for all scales and correlations between neuropsychologic tests and self-reported emotional and cognitive function (all p values < 0.05). There were significant negative correlations between the four factor scores derived from the HRQOL scales and neurotoxicity, systemic toxicity, and health care utilization (except for the correlation between mental health factor and health care utilization; all p values < 0.05). Patients who were seizure-free in the preceding year reported better HRQOL for the overall score, three of the four factor scores, and 8 of the 17 scale scores than did patients with a high frequency of seizures. Relative validity analysis showed that the epilepsy-targeted factor and three of its four component scales were more sensitive to categorization of patients by severity of seizure frequency and type than scales tapping physical health, mental health, or cognitive function. These cross-sectional data support the reliability and validity of this measure of HRQOL in epilepsy. The addition of an epilepsy-targeted supplement to the generic core improved the sensitivity to severity of epilepsy. The 86 items included in the field testing were supplemented by three additional items to form the Quality of Life in Epilepsy (QOLIE-89) inventory

OBJECTIVE: To examine the relationship of objectively assessed cognitive functioning to self-reported quality of life. DESIGN: Correlational, multiple regression, and factor analytic comparisons of a new self-report quality of life inventory with neuropsychological tests of cognition and mood. SUBJECTS: Two hundred fifty-seven patients with epilepsy. SETTING: Twenty-five epilepsy centers and neurology clinics across the United States. MEASURES: A recently developed self-report (ie, Quality of Life in Epilepsy-89 inventory) and objective tests of memory, verbal abilities, spatial functions, psychomotor and cognitive processing speed, cognitive flexibility, and mood. RESULTS: Factors that assessed mood, psychomotor speed, verbal memory, and language correlated significantly with selected scales of the Quality of Life in Epilepsy-89 inventory (P < .0001) and were predictive of overall quality of life (P < .002 to P < .0001). The mood factor showed the highest correlations (r = -.20 to r = -.73) and was the strongest predictor of quality of life in regression analyses (46.7% explained variance, P < .0001). CONCLUSIONS: Mood may be adversely affected by diminished quality of life, or perceived quality of life may be affected by mood disturbance. Quantitative quality of life assessments can be used in conjunction with formal neuropsychological testing of mood and cognition when evaluating patients with epilepsy

OBJECTIVE: To determine behavioral correlates of anterior cerebral artery (ACA) and posterior cerebral artery (PCA) perfusion patterns in the intracarotid amobarbital sodium procedure. DESIGN: Multivariate analysis of covariance and partial correlations of behavioral measures to ACA crossflow and PCA filling. SETTING: Angiography and the intracarotid amobarbital procedure at a comprehensive epilepsy center. SUBJECTS: Forty-two patients with intractable epilepsy (right-hemisphere seizure focus [n-23]; left-hemisphere seizure focus [n = 19]). MEASUREMENTS: Internal carotid angiography was performed both at a standard injection rate (8 mL of contrast per second) and at 1 mL/s, which matched the rate of the subsequent amobarbital injection. The degree of ipsilateral PCA and contralateral ACA filling were graded on a seven-point scale and compared with postinjection behavior, language, and memory measures. RESULTS: The ACA crossflow did not correlate significantly with that of any measure. The degree of PCA-filling pattern correlated significantly only with the level of consciousness (r = .31, P < .004), but it was not significant after accounting for the effects of seizure laterality, injection side, and amobarbital dosage. Neither ACA crossflow nor PCA filling correlated significantly with memory. The degree of ACA and PCA filling was overestimated at standard angiography (8 mL of contrast medium per second) injection rates. CONCLUSIONS: Although the degree of PCA filling correlates mildly with the level of consciousness postinjection, possibly by perfusion of thalamic or mesencephalic branches, it is not reliably predictive and is less contributory than the injection side and seizure laterality. The PCA filling is not required to produce valid memory assessment in the intracarotid amobarbital procedure, and ACA crossflow is not predictive of behavioral responses

We report two cases of ictal vomiting in patients who had left temporal lobe epilepsy. In one patient, vomiting developed when the discharge spread to the right temporal lobe as seen during depth electrode recording. In the second patient, ictal vomiting occurred with a restricted left temporal discharge, but the patient was left-handed and had right-hemisphere language dominance. These cases provide additional evidence of the involvement of the nondominant temporal lobe in ictus emeticus

The widespread use of video-electroencephalogram monitoring has dramatically increased our recognition of the high prevalence and diversity of nonepileptic seizures. Nonepileptic seizures stand squarely in the interface between psychiatry and neurology, an area that has been both claimed and denied by both sides. Collaborative exploration of this border zone has provided new insights into a disorder that may be as ancient as epilepsy

Eighteen patients with medically intractable Parkinson's disease that was characterized by bradykinesia, rigidity, and marked 'on-off' fluctuations underwent stereotactic ventral pallidotomy under local anesthesia. Targeting was aided by anatomic coordinates derived from the MRI, intraoperative cell recordings, and electrical stimulation prior to lesioning. A nonsurgically treated group of seven similarly affected individuals was also followed. Assessment of motor function was made at baseline and at 3-month intervals for 1 year. Following the lesioning, patients improved in bradykinesia, rigidity, resting tremor, and balance with resolution of medication-induced contralateral dyskinesia. When compared with preoperative baseline, all quantifiable test scores after surgery improved significantly with the patients off medications for 12 hours: UPDRS by 65%, and CAPIT subtest scores on the contralateral limb by 38.2% and the ipsilateral limb by 24.2%. Walk scores improved by 45%. Medication requirements were unchanged, but the patients who had had surgery were able to tolerate larger doses because of reduced dyskinesia. Ventral pallidotomy produces statistically significant reduction in parkinsonism and contralateral 'on' dyskinesia without morbidity or mortality and with a short hospitalization in Parkinson's disease patients for whom medical therapy has failed

Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)

OBJECTIVE: To determine the frequency and type of non-conversion nonepileptic seizures (NES). BACKGROUND: Although conversion disorder is the most common psychiatric disorder among patients with NES, many patients with nonepileptic paroxysmal behavioral events have other psychiatric disorders, with natural histories and treatments different from those of conversion disorder. DESIGN: Retrospective review of a series of consecutive admissions for video-electroencephalography monitoring. All patients identified with NES were interviewed by a psychiatrist. Patients with conversion and other psychiatric disorders were divided into separate groups. SETTING: A comprehensive epilepsy center. RESULTS: Twenty-one patients evaluated for possible epileptic seizures had a psychiatric disorder other than conversion that accounted for their events. Among these patients, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) anxiety disorders (n = 9) were the most common diagnosed category, followed by all forms of psychotic disorders (n = 7) and impulse control problems in the setting of attention deficit disorder residual type (n = 2). In contrast to 71 patients with conversion NES seen over the same period of time, the non-conversion group showed no female predominance and the nonconversion patients were significantly less likely than the conversion patients to have been physically or sexually abused in childhood or adolescence. CONCLUSIONS: These results support the validity of the nosologic distinction of nonconversion from conversion NES and suggest that DSM-III-R anxiety disorders are an important diagnostic confound in clinical epilepsy

Antidepressants or stimulants are commonly used to treat attention deficit disorder (ADD). We report the results of an open-label trial of the recently marketed antidepressant venlafaxine in 16 adult patients with ADD. Patients were treated with venlafaxine (25 to 225 mg/day) for 8 weeks. Four patients discontinued treatment within the first week because of sedation, agitation, or nausea. In the remaining 12 patients, venlafaxine treatment decreased ADD ratings by almost half

All antiepileptic drugs (AEDs) have the potential for adverse effects on cognition and behavior. Most of the major AEDs, administered in therapeutic doses, cause little or no cognitive or behavioral impairment in group studies. However, individual variability is considerable, and some patients do not tolerate low serum levels, whereas others tolerate high levels without subjective or objective effects. In the past, carbamazepine (CBZ) and valproate (VPA) have been reported to have the fewest adverse cognitive and behavioral effects in children and adults. However, several recent, well-controlled studies have not found significant differences between the effects of phenytoin (PHT) and those of CBZ or VPA. Greater adverse effects have been found for phenobarbital (PB). However, we must use environmentally relevant measures of cognitive and behavioral functioning to measure effects on daily functioning. Future studies must define cognitive and behavioral toxicity in subpopulations (e.g., post-traumatic epilepsy, mental retardation, depression) and with the new AEDs