Faculty Bibliography

OBJECTIVE: To measure the volume of basal forebrain septal nuclei in patients with temporal lobe epilepsy (TLE) as compared to patients with extratemporal epilepsy and controls. In animal models of TLE, septal lesions facilitate epileptogenesis, while septal stimulation is antiepileptic. METHOD: Subjects were recruited from 2 sites and consisted of patients with pharmacoresistant focal epilepsy (20 with TLE and mesial temporal sclerosis [MTS], 24 with TLE without MTS, 23 with extratemporal epilepsy) and 114 controls. Septal volume was measured using high-resolution MRI in association with newly developed probabilistic septal nuclei maps. Septal volume was compared between subject groups while controlling for relevant factors. RESULTS: Patients with TLE without MTS had significantly larger septal nuclei than patients with extratemporal epilepsy and controls. This was not true for patients with MTS. These results are interpreted with reference to prior studies demonstrating expansion of the septo-hippocampal cholinergic system in animal models of TLE and human TLE surgical specimens. CONCLUSION: Septal nuclei are enlarged in patients with TLE without MTS. Further investigation of septal nuclei and antiepileptic septo-hippocampal neurocircuitry could be relevant to development of new therapeutic interventions such as septal stimulation for refractory TLE.

Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury.

In the largest sample studied to date, we measured cognitive functioning in children and adolescents with pediatric multiple sclerosis (n = 187) as well as those with clinically isolated syndrome (n = 44). Participants were consecutively enrolled from six United States Pediatric Multiple Sclerosis Centers of Excellence. Participants had a mean of 14.8 +/- 2.6 years of age and an average disease duration of 1.9 +/- 2.2 years. A total of 65 (35%) children with multiple sclerosis and 8 (18%) with clinically isolated syndrome met criteria for cognitive impairment. The most frequent areas involved were fine motor coordination (54%), visuomotor integration (50%), and speeded information processing (35%). A diagnosis of multiple sclerosis (odds ratio = 3.60, confidence interval = 1.07, 12.36, P = .04) and overall neurologic disability (odds ratio = 1.47, confidence interval = 1.10, 2.10, P = .03) were the only independent predictors of cognitive impairment. Cognitive impairment may occur early in these patients, and prompt recognition is critical for their care.

The degree to which psychological factors are believed to influence the experience of pain has evolved significantly through history. Over the past 100 years, the trend has shifted from a focus on the study of sensory aspects of pain perception to one where psychological factors play a prominent role. Pain is now viewed as a complex subjective experience consisting of sensory, affective, and cognitive components. Psychological presentations of pain are commonly reduced to a differential among Pain Disorder, Somatization Disorder, and Malingering. Limitations in the use of the current DSM-IV-TR diagnostic classifications for pain will lead to changes in the upcoming DSM-V. Psychological testing is becoming increasingly recognized as a valuable evidence-based method for making diagnoses of psychological factors influencing pain presentations. There is a shift from the use of brief measures of pain intensity to multidimensional scales including assessment of affect and perceived functional disability. There is also increased attention to the use of validity scales for assessing symptom exaggeration and other types of response bias. Neuropsychologists, with specialized knowledge and background in evidence based assessment methods, are particularly well equipped to provide valuable input regarding psychological presentations of pain in forensic contexts and in consultation to multidisciplinary treatment teams.

The current study examined whether mood-congruent biases in emotion processing extend to epilepsy patients with depressive symptoms and the potentially moderating effects of age of seizure onset on these biases. In addition, we examined associations between depression (Beck Depression Inventory - 2nd Edition; BDI-II) and quality of life (Quality of Life in Epilepsy - 10-item questionnaire; QOLIE-10). Data from 101 epilepsy patients were analyzed, including 61 females and 40 males. Measures included the Comprehensive Affect Testing System - Abbreviated (CATS-A), from which indices of mood-congruent bias were derived. A significant interaction between BDI-II raw scores and age of seizure onset was found for mood-congruent bias scores in the facial affect modality (beta=-0.24, p<.03). Beck Depression Inventory - 2nd Edition raw scores were significantly and positively correlated with quality of life (QOLIE-10; r=.69, p<.01). Results of the current study show that epilepsy patients with an early age of seizure onset may be most at risk for mood-congruent biases when experiencing depressive symptoms and that such symptoms have real-world implications for quality of life for persons living with epilepsy.

BACKGROUND: Numerous anticonvulsant agents are now available for treating status epilepticus (SE). However, a paucity of data is available to guide clinicians in the initial treatment of seizures or SE. This study describes the current strategies being employed to treat SE in the USA. METHODS: Fifteen American academic medical centers completed a retrospective, multicenter, observational study by reviewing 10-20 of the most recent cases of SE at their institution prior to December 31, 2009. A multivariate analysis was performed to determine factors associated with cessation of seizures. RESULTS: A total of 150 patients were included. Most patients with SE had a seizure disorder (58 %). SE patients required a median of 3 AEDs for treatment. Three quarters of patients received a benzodiazepine as first-line therapy (74.7 %). Phenytoin (33.3 %) and levetiracetam (10 %) were commonly used as the second AED. Continuous infusions of propofol, barbiturate, or benzodiazepine were used in 36 % of patients. Median time to resolution of SE was 1 day and was positively associated with presence of a complex partial seizure, AED non-compliance prior to admission, and lorazepam plus another AED as initial therapy. Prolonged ICU length of stay and topiramate therapy prior to admission were negatively associated with SE resolution. Mortality was higher in patients without a history of seizure (22.2 vs 6.9 %, p = 0.006). CONCLUSIONS: The use of a benzodiazepine followed by an AED, such as phenytoin or levetiracetam, is common as first and second-line therapy for SE and appears to be associated with a shorter time to SE resolution. AED selection thereafter is highly variable. Patients without a history of seizure who develop SE had a higher mortality rate.