Faculty Bibliography

OBJECTIVE: This study was designed to further define the electroencephalographic abnormalities seen in the Landau-Kleffner syndrome variants and the associated clinical features. BACKGROUND: Landau-Kleffner syndrome is rare, but its putative variants are more common. METHOD: We report two patients with centro-temporal spikes, autistic epileptiform regression, and variably prominent oro-motor symptoms. RESULTS: The epileptic aphasia pattern found among patients with prominent Rolandic spikes may more frequently involve expressive language than is seen in the typical Landau-Kleffner syndrome, where verbal auditory agnosia is the rule. CONCLUSIONS: This clinical difference likely reflects the location of the epileptiform activity (centrotemporal as opposed to anterior or mid-temporal) on buccal-lingual function, vocalization, and language production

Repetitive vagal nerve stimulation (VNS) is a new, FDA-approved treatment for medically refractory epilepsy. The device is implanted subcutaneously in the left chest and sends intermittent impulses to the left vagus nerve through communicating leads. Twelve patients have been implanted to date. The ages of the patients range from 8 to 36 years and the average followup at this point is five months. Five patients have achieved a greater than 50 percent reduction in seizure frequency with no serious adverse effects

PURPOSE: To examine potential risk factors for poor health-related quality of life (HRQOL) among adolescents with epilepsy by using the newly developed QOLIE-AD-48. Risk factors were derived from sociodemographic, social, academic, and epilepsy- and health-related domains. METHODS: The QOLIE-AD-48 was administered to 197 English-speaking adolescents (age 11-17 years from >20 sites in the United States and in Canada). The self-report instrument yields an overall HRQOL score and eight subscale scores. Other data were obtained from family interviews, physician reports, and health records. Multiple regression analyses were conducted to study risk factors for impairment of HRQOL. RESULTS: Older adolescents (age 14-17 years), those with more severe epilepsy and more symptoms of neurotoxicity, and those living in households with lower socioeconomic status were more likely to report poor overall HRQOL. Risk factors in the eight HRQOL domains were found as follows: (a) Epilepsy Impact: older age in adolescence, more severe epilepsy and neurotoxicity, more hospitalizations during the past year, and fewer hours of extracurricular activities; (b) Memory and Concentration: longer duration of epilepsy, special education classes, and history of repeating a grade in school; (c) Attitude Toward Illness: older age, female gender, and more severe epilepsy and neurotoxicity; (d) Social Support: younger age, male gender, and fewer hospitalizations in the last year; (e) Stigma: lower socioeconomic status and special-education classes; and (f) Health Perceptions: older age, female gender, and lower socioeconomic status. None of the factors examined was significantly associated with HRQOL in (g) Physical Functioning or (h) School Behavior subscales. CONCLUSIONS: We identified several risk factors for poor HRQOL outcomes in adolescents with epilepsy. Age, increased seizure severity, and neurotoxicity were most consistently associated with poor HRQOL across domains. Older adolescents, independent of epilepsy severity, reported worse overall HRQOL than did their younger counterparts. Older adolescents also were more likely to perceive a greater negative impact on life and general health, and had more negative attitudes toward epilepsy. Adolescent boys and girls may show different sensitivities to various quality-of-life domains

The existence and specificity of a characteristic behavioral syndrome among patients with temporal lobe epilepsy (TLE) remains controversial. The behavioral pattern of many epilepsy patients differs from that of age-, sex-, and socioeconomic-matched control subjects. Patients with TLE and other forms of epilepsy can experience changes in cognitive function, personality, affect, and drive-related behavior (e.g., libido, aggression). Biologic factors (e.g., underlying brain pathology, epileptogenic process, localization and lateralization, recurrent seizures, family history), antiepileptic drugs, and psychosocial factors interact pathogenically. Their roles vary among patients and among different neurobehavioral disorders. Behavioral changes occur in some epilepsy patients. However, the question of whether specific behavioral changes occur with different seizure types or epilepsy syndromes remains unanswered. For example, behavioral changes can occur in patients with absence epilepsy, juvenile myoclonic epilepsy, frontal lobe epilepsy, and tonic-clonic seizures. Many of these behavioral changes overlap with features of the purported TLE syndrome. We lack a clear delineation of the spectrum, frequency, and severity of changes in well-characterized partial and primary generalized epilepsy syndromes. Furthermore, the relative roles and the interplay among pathogenic factors remain poorly defined

Studies of patients with psychogenic non-epileptic seizures (NES) typically focus upon the phenomenology and outcome of NES episodes. Little is known, however, about the frequency and nature of other somatic symptoms such as pain, in this population. To assess the frequency, location and severity of symptoms of pain among NES patients, we administered structured interviews to 56 patients, 6 or more months following the diagnosis of psychogenic non-epileptic seizures (NES). Patients were recruited from a tertiary hospital-based epilepsy monitoring unit. Seventy-seven percent of patients suffered from moderate to severe pain, most commonly headache (61%), while neck pain and backache were also common. Twenty-six of 27 patients with persistent NES vs. 17 of 29 patients whose NES resolved experienced moderate to severe pain (P < 0.001). Pain is an under-recognized problem that occurs frequently and with significant severity among NES patients. Pain symptoms are more common among patients with persistent NES than those whose NES resolve

The aim of this study was to assess prognosis among adult patients with nonepileptic seizures (NES) and to determine predictor variables for resolution of NES after diagnosis. Six to 9 months after receiving a video-EEG-documented diagnosis of NES, 43 adults responded by telephone interview to a detailed, structured questionnaire probing history of the episodes, psychiatric factors, socioeconomic variables, relationships, reactions to receiving the diagnosis, and potential history of litigation. At follow-up, only 18.6% were episode-free, 55.8% had improved, 16.3% reported no change, and 9.3% reported greater frequency of episodes. Patients who reported having many friends currently or having good relationships with friends as a child were significantly more likely to be episode-free. Subjects with pending litigation were significantly less likely to experience a reduction in episodes

OBJECTIVE: To determine the incidence of psychiatric adverse events associated with vigabatrin therapy, we reviewed data from US and non-US double-blind, placebo-controlled trials of vigabatrin as add-on therapy for treatment-refractory partial epilepsy. METHODS: 'Verbatim' terms from investigators' reports had been translated into standard 'preferred' terms using an adverse event dictionary. Terms for psychiatric events were then combined into categories for analysis of rates during vigabatrin versus placebo treatment. RESULTS: Compared with placebo, vigabatrin subjects had a higher incidence of events coded as depression (12.1% versus 3.5%, p < 0.001) and psychosis (2.5% versus 0.3%, p = 0.028); there were no significant differences between treatment groups for aggressive reaction, manic symptoms, agitation, emotional lability, anxiety, or suicide attempt. Although depression and psychosis were typically observed during the first 3 months, most studies were 12 to 18 weeks long, so that definitive conclusions could not be reached about timing of events. Psychosis was generally transient and reported to be responsive to reduction or discontinuation of vigabatrin or to neuroleptic treatment. Depression was typically mild. Serious depression, defined as discontinued from the study, hospitalized, or suicide attempt, or coded as psychotic depression, occurred in only 9 of the 49 vigabatrin-treated patients with depression. CONCLUSIONS: Vigabatrin use in treatment-refractory partial epilepsy is associated with increased occurrence of depression and of psychosis, although the frequency of psychosis is apparently lower than previously reported. Clinical experience suggests that these adverse events respond to reduction of vigabatrin dose or to counteractive psychotropic treatment

PURPOSE: To attain a comprehensive profile of clinical, psychiatric and psychosocial characteristics of patients with psychogenic nonepileptic seizures (NESs), and to assess the relation of these factors to NES outcome. METHODS: We administered a telephone-based structured questionnaire to 56 patients with NESs (16 male and 40 female patients; mean age, 35 years) at a mean follow-up time of 18 months after making the diagnosis of NES. RESULTS: Mean age of NES onset was 28 years with a mean duration of 8 years. Episodes resolved in 29 (51.8%) cases, decreased in 24 (42.9%), persisted unchanged in two (3.6%), and increased in frequency in one (1.8%). Thirty (53.6%) patients, including 13 (44.8%) of patients whose NESs resolved, were rehospitalized for NESs or for other symptoms. Twenty-nine (51.8%) had significant depressive symptoms, 22 (39.3%) had suicidal ideation, and 11 (19.6%) attempted suicide [including 6 (21%) of the patients whose NESs resolved]. Believing the NES diagnosis was associated with resolution or improvement of NES frequency (p<0.029), whereas anger in response to receiving the diagnosis did not predict a poorer outcome. Patients' perceptions of having good health (p<0.02) and good occupational functioning (p<0.04) were highly correlated with NES resolution. Only patients whose episodes resolved were employed at the time of follow-up. CONCLUSIONS: At a mean of 1.5 years, NES outcome was poor, with resolution in only half the group and with frequent rehospitalizations after NES diagnosis, even among patients whose NES resolved. Depressive symptoms, suicidal ideation, and suicide attempts were common. Believing the NES diagnosis and patient perceptions of having good health and good occupational functioning correlated well with NES resolution