Faculty Bibliography

Psychiatric disorders frequently occur in patients with epilepsy but the diagnosis is frequently missed and therapeutic opportunities are often lost. These comorbidities assume greater importance as epidemiological data show their frequent association with impaired function and quality of life, and advances in neurobiology better define their pathophysiological relationship and therapies. Epilepsy presents a model for understanding psychiatric illness. Deciphering the role of different biological and environmental risk factors may help identify high-risk patients and allow for early intervention. Antiepileptic drugs are frequently used to manage psychiatric syndromes although the mechanisms of their psychotropic action remain uncertain. As recognition and treatment of comorbid psychiatric disorders in epilepsy remain suboptimal, we need to increase the awareness of physicians, patients, their caregivers, and the health care system. Better recognition will help to develop and implement appropriate diagnostic and treatment programs, and improve functional outcomes and quality of life in people with epilepsy

We report two patients whose eating disorder resolved after right temporal lobe lesions. The first case report involves a woman with a history of bulimia nervosa and partial seizures arising from the occipital and right temporal regions. The second case is a woman with a history of anorexia nervosa that resolved after a head injury that resulted in right-sided inferofrontal and temporal encephalomalacia. Not only did both patients' eating disorders resolve, but their moods and libidos improved

Acute pathologic neurologic laughter has been described as an ictal phenomenon in epilepsy, as a result of electrical brain stimulation to the cortex and to deep brain structures, in brain tumors, and in stroke. We report what is, to our knowledge, the first report of a case of postictal pathologic laughter. Previously diagnosed with medically refractory complex partial seizures, our patient was admitted to the hospital with phenytoin toxicity. During video-EEG monitoring she experienced multiple brief absence seizures as well as a prolonged episode of absence status epilepticus. Immediately following cessation of the seizure she began to laugh. Her laughter was mirthful and infectious. This lasted several minutes and was followed immediately by several minutes of crying and then a return to normal. We propose that diffuse cortical inhibition led to release of subcortical structures involved in emotional expression. Possible neural substrates of laughter are discussed

Callosotomy has played a unique role in the treatment of epilepsy and in the understanding of human brain function. The pioneering work of Dejerine and Liepmann presenting the first findings of callosal lesion pathology at the turn of the 20th century was accepted but then quickly forgotten. Two schools resurrected the phoenix of callosal syndromes: Roger Sperry and Michael Gazzaniga leading in experimental neuroscience, and Norman Geschwind leading in clinical neurology. Callosotomy remains an effective technique to treat atonic, tonic, and tonic-clonic seizures, especially in patients with symptomatic generalized epilepsies such as Lennox-Gastaut syndrome. Neurologic, cognitive, and behavioral complications limit its use given that precise characterization of these complications as well as their frequency is difficult. The high frequencies of developmental delays, severe seizures, head injuries, antiepileptic drug burden, and other factors limit the ability to attribute a specific change to surgical intervention, since surgery can change multiple factors. For example, subtle behavioral changes in executive function and personality are difficult to delineate in a population with preexisting neurologic and psychiatric disorders. Despite this, a clearer picture of the effects of callosotomy, as defined by clinical neurology and neuropsychology as well as cognitive neuroscience, is emerging

Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha1 subunit (NaV1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. One previously reported GEFS+ mutation (I1656M) and an additional novel allele (R1657C), both affecting residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift in the voltage dependence of activation. Additionally, R1657C showed a 50% reduction in current density and accelerated recovery from slow inactivation. Unlike three other GEFS+ alleles that we recently characterized, neither R1657C nor I1656M gave rise to a persistent, noninactivating current. In contrast, two other GEFS+ mutations (A1685V and V1353L) and L986F, an SMEI-associated allele, exhibited complete loss of function. In conclusion, our data provide evidence for a wide spectrum of sodium channel dysfunction in familial epilepsy and demonstrate that both GEFS+ and SMEI can be associated with nonfunctional SCN1A alleles

PURPOSE: Women in the United States who have epilepsy give birth to about 20000 newborns every year. Because seizures during late gestation and delivery may seriously affect the fetus, and because primary generalized tonic-clonic (GTC) seizures may occur during labor and delivery in 1-2% of women with epilepsy, we attempted to define the rate, risks, and causes of seizures during labor and delivery. METHODS: To characterize seizures during labor and delivery, we retrospectively analyzed 89 consecutive pregnancies of women with epilepsy on antiepileptic drugs (AEDs). Six epileptologists in our group had treated these patients. We confirmed data and acquired new information by telephone for 83.1% of the pregnancies, and categorized the women as having primary generalized or partial epilepsy. Most of the patients (78%) were on monotherapy during pregnancy; 20% took two AEDs, and 3% took three AEDs during that period. RESULTS: Seizures during labor and delivery occurred in 4/32 (12.5%) patients with primary generalized epilepsy, but in none of the 57 women with partial epilepsy (P<0.05). None of the 38 patients with therapeutic AED levels before labor and delivery had seizures, compared to 3/37 (8.1%) of the subtherapeutic group. However, drug levels were taken at variable times in relation to delivery, limiting their value. Also, the levels sampled were both total and free levels; the latter would be more helpful to determine the adequacy of AED drug coverage. CONCLUSIONS: Maintaining therapeutic AED levels during the last trimester may help prevent seizures during labor and delivery, especially in women with generalized epilepsy. Women with epilepsy who had subtherapeutic AED levels and had been seizure-free may be at-risk for seizures during labor and delivery. Our sample was small, and a random sampling bias may have affected the results

PURPOSE: This report describes our long-term follow-up for combined resective surgery and multiple subpial transections (MSTs) in patients with refractory epilepsy involving eloquent and noneloquent cortex in multiple lobes. Multiple independent seizure foci made these patients poor candidates for conventional surgery. METHODS: MST and resective surgery were used in 13 patients to treat localization-related refractory epilepsy involving eloquent and noneloquent cortex of two or more lobes. Preoperative investigation was followed by invasive monitoring. RESULTS: Eleven patients had MST plus resection involving two different lobes, and two patients had MST plus resection involving three different lobes. MSTs were performed on the primary sensorimotor cortex (eight patients), temporal language area (two patients), Broca's area (one patient), and on both frontal motor and temporal language areas (two patients). Nine patients had a two-stage procedure, and four patients had a three-stage procedure (two consecutive subdural grid studies followed by resections). Average follow-up was 59.2 months (range, 42-98 months). With a modified Engel Outcome Scale, four patients (31%) had a class I outcome; three (23%), class II; three (23%), class III; and three (23%), class IV. Ten (77%) patients had a >50% reduction of seizure burden. CONCLUSIONS: Combined MST and resection can meaningfully improve seizure control in patients with multifocal epilepsy involving eloquent cortex. Prospective randomized studies are needed