Faculty Bibliography

Postictal psychosis is characterized by a fluctuating combination of thought disorder, auditory and visual hallucinations, delusions, paranoia, affective change, and aggression including violent behavior. We present a case of homicide following a cluster of seizures. The patient's history and postictal behavior were his consistent with postictal psychosis. Contributing factors resulting in homicide may have included increased seizure frequency associated with a change in his AED regimen seizure frequency. The AED change to levetiracetam may also have increased impulsiveness with diminished mood regulation following discontinuation of carbamazepine. There is evidence that he had a cluster of seizures immediately prior to the murder which may have resulted in the postictal disinhibition of frontal lobe inhibitory systems. This homicide and other violent behaviors associated with postictal psychosis may be avoided with earlier recognition and treatment.

Magnetic resonance imaging (MRI) techniques have been used to quantitatively assess focal and network abnormalities. Idiopathic generalized epilepsy (IGE) is characterized by bilateral synchronous spike-wave discharges on electroencephalography (EEG) but normal clinical MRI. Dysfunctions involving the neocortex, particularly the prefrontal cortex, and thalamus likely contribute to seizure activity. To identify possible morphometric and functional differences in the brains of IGE patients and normal controls, we employed measures of thalamic volumes, cortical thickness, gray-white blurring, fractional anisotropy (FA) measures from diffusion tensor imaging (DTI) and fractional amplitude of low frequency fluctuations (fALFF) in thalamic subregions from resting state functional MRI. Data from 27 patients with IGE and 27 age- and sex-matched controls showed similar thalamic volumes, cortical thickness and gray-white contrast. There were no differences in FA values on DTI in tracts connecting the thalamus and prefrontal cortex. Functional analysis revealed decreased fALFF in the prefrontal cortex (PFC) subregion of the thalamus in patients with IGE. We provide minimum detectable effect sizes for each measure used in the study. Our analysis indicates that fMRI-based methods are more sensitive than quantitative structural techniques for characterizing brain abnormalities in IGE.

OBJECTIVE: Describe the characteristics of persons with epilepsy (PWEs) and caregivers that have or have not heard of sudden unexpected death in epilepsy (SUDEP) prior to completing a survey through the Internet or in the clinical setting. METHODS: An online survey for adult PWEs and caregivers was solicited by e-mail and newsletter to Epilepsy Therapy Project members. A similar survey was implemented in a clinic setting of a community hospital. The survey asked about seizure characteristics, epilepsy management, fear of death, and familiarity with the term SUDEP. Respondents that never heard of SUDEP read a definition and responded to questions about their initial reactions. RESULTS: Surveys from 1,392 PWEs and 611 caregivers recruited through an epilepsy Website and a clinic demonstrated that Internet respondents were much more likely to have heard about SUDEP than the clinic population (71.1% vs. 38.8%; p < 0.001), and caregivers of PWEs were more likely to have heard about SUDEP than PWEs (76.2% vs. 65.2%; p < 0.001). Prior awareness was related to an increased level of education, more severe and longer duration of epilepsy, and having an epileptologist as the primary care provider. Although most PWEs and caregivers reported feelings of fear, anxiety, and sadness after first hearing of SUDEP, they wanted to discuss it with their doctor. Persons with epilepsy, and especially their caregivers, often worry that the PWEs may die of epilepsy or seizures. This worry escalated with knowledge of SUDEP and increased epilepsy severity. Approximately half of PWEs and caregivers believed that knowledge about SUDEP would influence their epilepsy management. SIGNIFICANCE: Our results may help epilepsy care providers determine when to facilitate a discussion about epilepsy-related mortality and SUDEP among patients and caregivers, and to educate those at high risk about the importance of seizure control as well as reduce fears about death in patients with well-controlled and nonconvulsive epilepsies.

Integrated PET/MR with simultaneous acquisition may improve the identification of pathologic findings in patients. This pilot study evaluated metabolic activity differences between epilepsy patients and healthy controls and directly correlated FDG uptake with MR regional abnormality. Epilepsy patients (n=11) and controls (n=6) were imaged on a whole-body simultaneous PET/MR scanner. After FDG injection, simultaneous images were acquired for 60 minutes. Statistical analyses on SUV values (over 117 brain regions, including left and right, for 96 cortical and 21 subcortical regions) derived from three normalization methods, by individual subject's mean cortical, white matter or global brain, were compared between groups. The asymmetry was compared. T2, T1 and PET co-registered images were also used for lesion detection and correlation of PET and MR regional abnormality. Left and right postcentral gyri were found to be consistently hypermetabolic regions, while right temporal pole and planum polare were consistently hypometabolic regions by all three normalization methods. Using the asymmetry index (AI > 10% or SUV ratios > 1.2), more metabolic asymmetry regions were detected in patients than in controls, with 96.2% agreement. The presence of hippocampal abnormalities or cortical tubers detected via T2 FLAIR in patients correlated well with the hypometabolism detected via FDG-PET. Our results showed specific patterns of metabolic abnormality and asymmetry over 117 brain regions in epilepsy patients, as compared to controls, suggest that simultaneous PET/MR imaging provides a useful tool to help understand etiopathogenesis and localize seizure foci.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) commonly present with significant neurologic deficits, including seizures, autism, and intellectual disability. Previous evidence suggests that the TSC2 mutation genotype may be associated with a more severe disease phenotype. This study evaluates the association of the TSC1 and TSC2 genotype with patient and disease characteristics in a retrospective review of a large TSC Natural History Database consisting of 919 patients with TSC. METHODS: Univariate logistic regression was conducted to evaluate the association of the TSC1 and TSC2 gene mutations with patient and disease characteristics. RESULTS: As compared to patients with the TSC1 mutation, patients with the TSC2 mutation were younger (p = 0.02), more likely to have partial epilepsy (odds ratio (OR) 1.74, p = 0.0015), complex partial seizures (OR 2.03, p = 0.02), infantile spasms (IS) (OR 1.67, p = 0.01), subependymal giant-cell astrocytomas (SEGAs) (OR 1.64, p = 0.01), and intellectual disability (OR 2.90, p = 0.0002). SIGNIFICANCE: The clinical presentation of TSC is highly variable and not well understood. Our findings confirm and supplement existing literature that TSC2 mutation is likely to be associated with a more severe, earlier presenting TSC phenotype, including infantile spasms. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Intractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa. Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports. Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment-resistant epilepsy. A first step in this direction is to systematically investigate the safety, pharmacokinetics, and interactions of CBD with other antiepileptic drugs and obtain an initial signal regarding efficacy at different dosages. These data can then be used to plan double-blinded placebo-controlled efficacy trials. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Delta9 -Tetrahydrocannabinol (Delta9 -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and Delta9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Delta9 -THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the alpha3 and alpha1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:Delta9 -THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.