Faculty Bibliography

Neurobehavioral disorders commonly affect patients with epilepsy. In addition to the behavioral changes during and immediately after seizures, the epileptogenic disorder of function often extends further into the postictal and interictal period. Cognitive impairments commonly affect attention, memory, mental speed, and language, as well as executive and social functions. Reducing seizure frequency and the antiepileptic drug burden can reduce these problems. Attentional deficits may respond to therapies for attention-deficit/hyperactivity disorder, but apart from patients with this comorbid disorder, their efficacy is unproven in other epilepsy patients. No effective therapies are established for other cognitive problems, but pragmatic, compensatory strategies can be helpful. Behavioral disorders include fatigue, depression, anxiety, and psychosis. Many of these disorders usually respond well to pharmacotherapy, which can be supplemented by psychotherapy. Cognitive and behavioral disorders can be the greatest cause of morbidity and impaired quality of life, often overshadowing seizures. Yet these problems often go unrecognized and, even when identified, are often undertreated or untreated

Nonepileptic seizures (NES) are neuropsychiatric disorders presenting with a combination of neurologic signs and underlying psychological conflicts. For more than a century, the medical community has accumulated data and insights about the phenomenology, epidemiology, risks, comorbidities, and prognosis of NES. However, we have not progressed much beyond anecdotal reports of treatments for NES, and no randomized, controlled trials of treatment for the disorder have been conducted. We review the diagnosis and treatment of NES and suggest directions for future research in these areas

Of the 1,200,000 Americans with partial epilepsy, temporal lobe epilepsy (TLE) occurs in more than 400,000. Temporal lobe seizures are usually stereotypic in their symptoms and duration. A typical sequence is an aura followed by arrest of motor behavior, blank stare, and automatisms. Patients with TLE often show impairments in attention, memory, mental processing speed, executive functions, mood, personality, and drive-related behaviors. Interictal depression occurs in approximately one third of TLE patients. TLE is diagnosed by a history of characteristic partial seizure symptoms. The diagnosis is confirmed by the capture of a typical episode during an electroencephalogram (EEG) or video-EEG, with epileptiform activity over one or both temporal regions. Video-EEG monitoring has revolutionized diagnosis and should be considered in patients in whom diagnosis is uncertain. TLE is treated with medications, resective surgery, and vagus nerve stimulation. Epilepsy surgery should be considered in all patients with refractory partial epilepsy

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

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