Jeffrey B. Titus

Depression and anxiety in children and adolescents with epilepsy: prevalence, risk factors, and treatment.

Among the psychiatric comorbid conditions in children and adolescents with epilepsy, depression and anxiety disorders require further attention because they carry the risk of reduced quality of life and life-threatening complications (e.g., suicide). Research in recent years has shed light on both the prevalence of emotional problems in youth with epilepsy and the safety and efficacy of treatment options. A number of challenges exist in treating patients with epilepsy. This is particularly true when seizures are difficult to control and medication regimens are more complex. Some pharmaceutical options may provide assistance with both seizures and emotional distress, but care is needed when considering such treatment approaches. In addition, integration of mental health professionals into the care of patients is necessary when cases are complicated and risk factors are high. Thorough methods to accurately diagnose emotional conditions and regular monitoring of symptoms can help prevent serious problems that can negatively affect the success of children and adolescents in everyday life. Collaboration between disciplines offers the best hope for early identification and treatment of these conditions.

Examining health-related quality of life, adaptive skills, and psychological functioning in children and adolescents with epilepsy presenting for a neuropsychological evaluation

The purpose of this study was to characterize 132 children and adolescents (mean age = 10 years, 11 months) with epilepsy in terms of psychosocial functioning and to determine the extent to which adaptive skills and psychological functioning predict health-related quality of life (HRQOL), above and beyond demographic and epilepsy-specific characteristics. A chart review was conducted to obtain demographic and epilepsy-specific information as well as caregiver responses on the Behavior Assessment System for Children, Second Edition (BASC-2) Parent Report and the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). In addition to Full Scale IQ and age at seizure onset, the BASC-2 Clinical and Adaptive Skills subscales also predicted HRQOL, indicating that this measure may be particularly helpful in predicting HRQOL above and beyond information routinely collected in a medical setting. It is imperative to evaluate children with epilepsy for psychosocial difficulties and diminished HRQOL to ensure the provision of comprehensive quality care and intervention services.

Attention Skills in Children With Neurofibromatosis Type 1

Children with neurofibromatosis type 1 are at increased risk for the development of attention problems relative to their unaffected peers. Previous studies have reported deficits in sustained auditory attention, but other aspects of attention, including sustained visual attention, divided attention, response inhibition, and selective attention, have not been consistently documented. In the present study, we specifically investigated attention skills in children with neurofibromatosis type 1 using measures of visual and sustained auditory attention, divided attention, selective attention, and response inhibition. Consistent with previous reports, we confirmed the presence of deficits in sustained visual and auditory attention in children with neurofibromatosis type 1 but also identified deficits in divided attention and response inhibition. Based on the high frequency and wide spectrum of attention system impairments in this at-risk population, we advocate screening children with neurofibromatosis type 1 for attention problems and providing appropriate interventions that address all aspects of their executive functioning.

Extratemporal, nonlesional epilepsy in children: postsurgical clinical and neurocognitive outcomes

OBJECT Patients undergoing epilepsy surgery without evidence of a lesion on MR imaging and without a temporal source for seizure onset generally have less favorable outcomes than patients with structural lesions or temporal onset. However, many of these patients are viable candidates for invasive monitoring and subsequent resection or multiple subpial transections (MSTs). The purpose of this study was to evaluate the surgical treatment of pediatric patients with extratemporal, nonlesional epilepsy in order to better understand the clinical and neuropsychological outcomes expected in this patient group. METHODS Forty-three pediatric patients with negative results on MR imaging and lateralized, extratemporal findings on electroencephalography underwent invasive monitoring with grid and/or strip electrodes. Thirty-three subsequently had resection of an epileptogenic focus and/or MSTs. RESULTS Outcome was classified as Engel class I or II in 54.5% of the patients who underwent resection/MSTs and Engel class III or IV in 45.5%. Use of MSTs was associated with poor outcome. Neuropsychological evaluation showed significant improvement in immediate auditory attention following surgery and revealed several significant results on subgroup analysis. Complications occurred in 14% of patients (a 7% rate per procedure). Ten patients (23%) underwent invasive monitoring without proceeding to therapeutic surgery because no epileptogenic region was amenable to resection. Neuropsychological outcomes were generally stable. CONCLUSIONS Patients with extratemporal, nonlesional seizures are viable candidates for invasive monitoring with grid/strip electrodes, and good outcomes can be obtained with resective surgery. The use of MSTs may correlate with worse outcome. This study also provides additional data to assist in counseling patients on the risks of negative invasive monitoring, deficits resulting from resection/MSTs, and possible operative complications.

Health-related quality of life before and after pediatric epilepsy surgery: The influence of seizure outcome on changes in physical functioning and social functioning

Health-related quality of life (HRQOL) is an important outcome in pediatric epilepsy surgery, but there are few studies that utilize presurgical ratings to assess the effect of surgery on HRQOL. We collected parental ratings on the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 28 children who participated in neuropsychological assessment before and after epilepsy surgery. Our results revealed significant improvements in overall HRQOL after surgery, especially in physical and social activities. These changes were apparent despite generally unchanged intellectual and psychological functioning. Children with better seizure outcome had more improvement in HRQOL; however, improvements were not statistically different among children with Engel class I, II, and III outcomes. Our results suggest that children can experience significant improvements in HRQOL following epilepsy surgery even when neuropsychological functioning remains unchanged. Moreover, improvements in HRQOL appear evident in children who experience any worthwhile improvement in seizure control (Engel class III or better).

Palliative hemispherotomy in children with bilateral seizure onset.

OBJECT Intractable epilepsy is a significant burden on families and on the cognitive development and quality of life (QOL) of patients. Periinsular hemispherotomy (PIH) for medically intractable epilepsy can benefit patients who qualify for this procedure. The ideal hemispherotomy candidate has ipsilateral ictal and interictal epileptiform activity, unilateral MR imaging abnormalities, contralateral hemiplegia, and a normal contralateral hemisphere. However, certain patients present with a mixed picture of bilateral electroencephalography (EEG) findings and severe intractable epilepsy, prompting consideration of a more aggressive treatment approach. This report introduces the possibility of surgery for patients who normally would not meet criteria for this treatment modality. METHODS In this retrospective chart review, the authors report on 7 patients with bilateral seizure onset noted on routine or video-EEG monitoring. A QOL phone questionnaire, based on the Quality of Life in Childhood Epilepsy tool, was administered to a parent. The authors reviewed each patients chart for surgical complications, changes in examination, QOL, limited neuropsychological outcomes, and seizure outcomes. They also investigated each chart for MR imaging and EEG findings as well as the patients epilepsy clinic notes for seizure semiology and frequency. RESULTS All patients enjoyed a decrease in seizure frequency and a subjective increase in QOL after PIH. Five patients (71%) achieved Engel Class I or II seizure control. The mean follow-up was 3.64 years (2-5.3 years). One patient is now off all antiseizure medication. No patient had a decrement in Full Scale IQ on postsurgical testing, and 2 (28.5%) of 7 individuals had increased adaptive and social functioning. Postsurgical examination changes included hemiplegia and homonymous hemianopia. CONCLUSIONS Hemispherotomy in patients with intractable epilepsy is generally reserved for individuals with unilateral epileptiform abnormalities or lesions on MR imaging. Seven patients in this study benefited from surgery despite bilateral seizure onset with improvement in seizure control and overall QOL. Thus, bilateral ictal onset does not necessarily preclude consideration for hemispherotomy in selected patients with severe medically refractory epilepsy.

A Neuropsychological Perspective on Attention Problems in Neurofibromatosis Type 1

Cognitive problems are common in children with neurofibromatosis type 1 and they can often complicate treatment. The current literature review examines cognitive functioning in neurofibromatosis type 1, with a specific focus on executive functioning. This includes exploration of how deficits in executive functioning are expressed in children with neurofibromatosis type 1 and how these deficits contrast with ADHD. The value of investigating subcomponents of executive functioning is discussed, as are implications for effective treatment and future research.

Executive function and health-related quality of life in pediatric epilepsy.

Children and adolescents with epilepsy often show higher rates of executive functioning deficits and are at an increased risk of diminished health-related quality of life (HRQOL). The purpose of the current study was to determine the extent to which executive dysfunction predicts HRQOL in youth with epilepsy. Data included parental ratings on the Behavior Rating Inventory of Executive Function (BRIEF) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 130 children and adolescents with epilepsy (mean age=11years, 6months; SD=3years, 6months). Our results identified executive dysfunction in nearly half of the sample (49%). Moderate-to-large correlations were identified between the BRIEF and the QOLCE subscales of well-being, cognition, and behavior. The working memory subscale on the BRIEF emerged as the sole significant predictor of HRQOL. These results underscore the significant role of executive function in pediatric epilepsy. Proactive screening for executive dysfunction to identify those at risk of poor HRQOL is merited, and these results bring to question the potential role of behavioral interventions to improve HRQOL in pediatric epilepsy by specifically treating and/or accommodating for executive deficits.

The relationship of seizure focus with depression, anxiety, and health-related quality of life in children and adolescents with epilepsy

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age=11.34, SD=3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy.

The influence of endophenotypic, disease-specific, and environmental variables on the expression of anxiety in pediatric epilepsy

Children and adolescents with epilepsy often show higher rates of anxiety, which carries an increased risk for reduced health-related quality of life (HRQOL). The current study assessed the role of parental psychiatric history (i.e., anxiety, depression, and/or bipolar disorder) on the rate of anxiety features in youth seen in a tertiary epilepsy clinic. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 180 children and adolescents (mean age=11.40, SD=3.98). Our results identified clinically elevated anxiety ratings in nearly half the sample (47%) with previous psychiatric history endorsed by 48% of parents. The effect of parental psychiatric history on youth anxiety was found to be significant and associated with a threefold increase in the rate of youth anxiety features. This risk increased to fourfold in refractory epilepsy, and the impact of family psychiatric history is greater in adolescent females and in families that report higher levels of stress. In those families who reported no psychiatric history, anxiety was best predicted by epilepsy-specific factors above and beyond sociodemographic factors. Parental psychiatric history was also identified as a significant risk factor for diminished patient HRQOL, even after accounting for seizure control. These findings highlight the impact of family and epilepsy factors on psychological functioning and offer further support for the strong relationship between parental adjustment and child outcome in pediatric epilepsy.