David A. Muzykewicz

The natural history of epilepsy in tuberous sclerosis complex

Background:  Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease.

Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy

Purpose:  To report the efficacy, safety, and tolerability of the low glycemic index treatment (LGIT) in pediatric epilepsy.

Psychiatric comorbid conditions in a clinic population of 241 patients with tuberous sclerosis complex.

Psychiatric symptoms were retrospectively assessed in a clinic population of 241 children and adults with tuberous sclerosis complex (TSC). Sixty-six (27%) patients had a history of mood disorder symptoms, 66 (27%) had a history of anxiety disorder symptoms, 73 (30%) had a history of attention-deficit hyperactivity disorder (ADHD) symptoms, and 68 (28%) had a history of aggressive/disruptive behavior disorder symptoms. Significant relationships were found between these symptoms and patient age, gender, genetic mutation, seizure history, surgical history, cognitive impairment, features of autism or pervasive developmental disorder, and neurological manifestations of TSC. In 43 patients seen by at least one of two affiliated psychiatrists, the most common formal diagnoses were anxiety disorders (28%), mood disorders (26%), adjustment disorders (21%), ADHD (21%), and mental disorders not otherwise specified due to general medical condition (42%). Citalopram demonstrated efficacy in treating anxiety and depression, and risperidone, in treating problematic behaviors.

Infantile spasms in tuberous sclerosis complex: prognostic utility of EEG.

Purpose:  To assess cognitive and epilepsy outcomes in tuberous sclerosis complex (TSC) patients with a history of infantile spasms (IS), in relation to spasm history, electroencephalography (EEG) characteristics, genetic mutation, and treatment history.

A karate program for improving self-concept and quality of life in childhood epilepsy: Results of a pilot study

The potential cognitive and psychosocial effects of childhood epilepsy have significant implications for a childs self-image and academic achievement. This study focuses on a 10-week karate program for children and adolescents with epilepsy aimed at increasing social confidence, self-concept, and quality of life, as well as reducing parental anxiety. Eleven children (8-16 years old) and their parents participated in this questionnaire study, and complete data were available for nine of these families. Measures consisted of the Piers-Harris Childrens Self-Concept Scale, the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire, and the Parental Stress Index. By parental report, significant improvement in memory function and largely positive trends in quality of life on multiple subscales were observed. By child report, intellectual self-esteem and social confidence also improved. Parental stress decreased, although not significantly, suggesting a potential benefit and indicating a role for future interventions targeting family anxiety.

Behavior problems in children with tuberous sclerosis complex and parental stress

Behavioral problems are common in children with tuberous sclerosis complex (TSC) and can be challenging to manage at home. Standardized measures were used to assess behavior in 99 pediatric patients with TSC and to evaluate parenting stress in their parents. About 40% of the pediatric patients presented clinically significant behavioral problems, most frequently involving symptoms of autism spectrum disorder, inattention, and hyperactivity. Higher seizure frequency, mixed seizure disorder, and low intellectual functioning placed the patient at significant risk for behavior problems. Almost 50% of participating parents reported experiencing clinically significant parenting stress, which was associated with specific characteristics of the child, including the presence of current seizures, a history of psychiatric diagnosis, low intelligence, and behavioral problems. Clinicians should be aware that behavioral problems are prominent in children with TSC. Referrals for behavioral intervention and monitoring of parental stress should be included in the medical management of children with TSC.

TSC1 and TSC2 mutations in patients with lymphangioleiomyomatosis and tuberous sclerosis complex

Background: Lymphangioleiomyomatosis (LAM) is a prominent finding in the setting of tuberous sclerosis complex (TSC). Objective: The present study was designed to compare cystic lung changes consistent with LAM in patients with a TSC1 disease-causing mutation, TSC2 disease-causing mutation, or no mutation identified (NMI). Methods and results: We conducted a retrospective review of the chest computed tomography (CT) of 45 female and 20 male patients with TSC and found cysts consistent with LAM in 22 (49%) women and two (10%) men. In the female population, changes consistent with LAM were observed in six of 15 (40%) patients with TSC1, 11 of 23 (48%) with TSC2, and five of seven (71%) with NMI. While the predominant size of cysts did not differ across these three groups, TSC2 women with LAM had a significantly greater number of cysts than did TSC1 patients (p = 0.010). Conclusions: These findings suggest a higher rate of LAM in TSC1 than previously recognised, as well as a fundamental difference in CT presentation between TSC1 and TSC2.

Self-injurious behavior and tuberous sclerosis complex: frequency and possible associations in a population of 257 patients

Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC and determined possible associations with SIB. We found a 10% frequency of SIB in our TSC population. When compared with patients without psychiatric symptoms, we identified a significantly higher rate of electroencephalographic interictal spikes in the left frontal lobe and a significantly lower number of tubers in the left occipital, parietal, and posterior temporal lobes. We also found that frequency of TSC2 mutation, history of infantile spasms, history of seizures, mental retardation, and autism are significantly associated with SIB.

Associations between electroencephalographic and magnetic resonance imaging findings in tuberous sclerosis complex

Nearly 90% of patients with tuberous sclerosis complex (TSC) develop epilepsy; however the mechanisms of epileptogenesis remain unclear. Some cortical tubers are thought to be epileptogenic while others are not. This study aimed to evaluate whether tuber burden, size or type seen on magnetic resonance imaging (MRI) co-registers with interictal epileptiform discharges on electroencephalogram (EEG). EEG and MRI data from 69 patients with TSC were reviewed by dividing the cerebrum into four quadrants. Quadrants containing greatest tuber burden, largest tuber, calcified tubers, cyst-like tubers, and no tubers were identified on MRI. For EEG analysis, spikes and sharp waves were counted and averaged to a value per minute, and each quadrant was assigned a score. MRI and EEG findings were compared in each patient. The presence of a cyst-like tuber in a quadrant correlated with a higher incidence of epileptiform activity in the same quadrant (p=0.002). This finding supports the notion that cyst-like cortical tubers may contribute to the more severe epilepsy profile seen in TSC patients with these lesions. Quadrants containing greatest tuber burden, largest tubers, and calcified tubers were not predictive of regional interictal epileptiform activity. Furthermore, quadrants without any apparent tuber co-registered with interictal epileptiform discharges in two patients, suggesting a multifactorial component of epileptogenicity in TSC.

Multifocal micronodular pneumocyte hyperplasia: computed tomographic appearance and follow-up in tuberous sclerosis complex.

Objective To characterize pulmonary nodules in patients with tuberous sclerosis complex (TSC) using computed tomography. Methods We retrospectively reviewed chest computed tomographic images of 73 patients with TSC (22 males and 51 females; mean ± SD age, 31.5 ± 13.2 years; range, 13.8–63.5 years). Results Multiple pulmonary nodules were identified in 42 (58%) of 73 patients (mean ± SD size, 6.6 ± 3.0 mm; range, 2–14 mm). Solid nodules were present in 11 (26%) of 42 patients, ground-glass nodules were present in 3 (7%) of 42 patients, and both solid and ground-glass nodules were present in 28 (67%) of 42 patients. The presence of multiple nodules was independent of sex and lymphangioleiomyomatosis. Follow-up images were available for 22 patients with multiple nodules (mean ± SD follow-up, 2.0 ± 1.1 years; range, 0.9–4.9 years), none of whom had change in nodule size or number. Conclusions Most men and women with TSC have multiple pulmonary nodules, which likely represent multifocal micronodular pneumocyte hyperplasia in the absence of known predisposing factors.