Faculty Bibliography

Rationale: Controversy remains as to whether or not neurologists should discuss SUDEP with all epilepsy patients or only those at high risk. We initiated a web-based survey to determine whether persons with epilepsy (PWE) and caregivers of PWE (C-PWE) want to know about SUDEP from their medical providers and when they want to learn about it. Methods: An online survey for adult PWE and C-PWE was designed based on a previous survey of neurologists (Friedman et al, 2012; AES abstract). Respondents were solicited from an email blast and newsletter sent to Epilepsy Therapy Project (ETP) members. A survey link was also posted on epilepsy.com. The survey was IRB approved. Results: 1,325 PWE and 574 C-PWE completed at least some of the survey. Demographic features and epilepsy-related factors are summarized in Table 1Attitudes and knowledge of SUDEP are summarized in Table 2Of the PWE respondents. 57% worry at least a little about dying from their epilepsy and 68% heard about SUDEP before the survey. of these 68%, 52% learned of SUDEP from the internet, only 9.6% from their epilepsy doctor; only 29% feel welleducated about it; 46% don't know whether they are at risk; and 69% never discussed SUDEP with their doctor. of the 32% who had not heard of SUDEP, 50% were scared, anxious or sad after reading the definition but only 3% did not want to ever be told about SUDEP. 65% will go to their epilepsy doctor for more information. of the responding C-PWE, 92% worry at least a little about the PWE dying from epilepsy. 80% had heard about SUDEP before our survey and 55% of these learned about it from the internet and 11.8% from the epilepsy doctor. Only 28% felt well-educated about it; 64% think the PWE is at risk for SUDEP; and 55% never discussed SUDEP with the doctor. of the 20% that had not heard of SUDEP prior to our survey, 92% were scared, anxious or sad after reading the definition but only 1% did not want to ever be told about SUDEP. 83% will go to their epilepsy doctor for more information. Conclusion!

Rationale: Autism spectrum disorders (ASDs), characterized by impaired social interactions, impaired communication and stereotyped behaviors, are highly associated with epilepsy (up to 38%). A shift in cortical excitatory/inhibitory balance towards increased excitation and/or decreased inhibition may play a key role in the pathophysiology of both ASDs and epilepsy. We hypothesized that differences in AMPA receptor (AMPAR) and NMDA receptor (NMDAR) subunit expression in ASD and epilepsy patients may represent a basis for distinct clinical neurological manifestations. Identifying specific synaptic mechanisms for autism and epilepsy will allow development of targeted therapies. Methods: Brain specimens from treatment-resistant temporal lobe epilepsy cases were collected prospectively during resective surgery at NYULMC (n=5; ages 21-37 years). Autopsy temporal and frontal lobe samples from ASD patients (n=5; ages 4-22 years) and regionmatched control specimens from cases with normal neurological history (n=10; ages 5-48 years) were obtained from Maryland Brain and Tissue Bank. All ASD cases met the standard diagnostic criteria (Autism Diagnostic Interview-Revised) and had no evidence of epilepsy, while none of the epilepsy patients were diagnosed with autism. The levels of the NMDAR and AMPAR subunits (NR1, NR2A, NR2B, GluR1 and GluR2) were quantified by Western blot and compared among groups (one-way ANOVA and t-tests). Results: Temporal lobe cortex analysis demonstrated a significant increase in NR1 expression in autism patients (288% of control; p<0.0001), but no significant change in epilepsy cases (96% of control; p>0.05). In both groups, NR2A was significantly decreased (ca. 40% of control; p<0.0001), while NR2B demonstrated a significant upregulation (255% of control in autism and 511% of control in epilepsy; p<0.0001). NR2B levels were significantly higher in epilepsy, relative to autism patients (p<0.001). GluR1 expression was increased in both autism (388% of control; p<0.0001) and epilep!

PURPOSE: To review the efficacy and tolerability of stiripentol in the treatment of U.S. children with Dravet syndrome. METHODS: U.S. clinicians who had prescribed stiripentol for two or more children with Dravet syndrome between March 2005 and 2012 were contacted to request participation in this retrospective study. Data collected included overall seizure frequency, frequency of prolonged seizures, and use of rescue medications and emergency room (ER)/hospital visits in the year preceding stiripentol initiation, and with stiripentol therapy. We separately assessed efficacy in the following treatment groups: group A, stiripentol without clobazam or valproate; group B, stiripentol with clobazam but without valproate; group C, stiripentol with valproate but without clobazam; and group D, stiripentol with clobazam and valproate. In addition, adverse effects were recorded. KEY FINDINGS: Thirteen of 16 clinicians contacted for study participated and provided data on 82 children. Stiripentol was initiated a median of 6.0 years after seizure onset and 1.2 years after diagnosis of Dravet syndrome. Compared to baseline, overall seizure frequency was reduced in 2/6 in group A, 28/35 in group B, 8/14 in group C, and 30/48 in group D. All children with prolonged seizure frequency greater than quarterly during the baseline period experienced a reduction in this frequency on the various treatment arms with stiripentol. Similarly, 2/4 patients in group A, 25/25 in group B, 5/10 in group C, and 26/33 in group D experienced reduction in frequency of rescue medication use and 1/1 in group A, 12/12 in group B, 3/5 in group C, and 18/19 in group D had reduction in frequency of ER/hospital visits. Adverse effects were reported in 38, most commonly sedation and reduced appetite. Four patients (5%) discontinued stiripentol for adverse effects and two (2%) for lack of efficacy. SIGNIFICANCE: Stiripentol is an effective and well-tolerated therapy that markedly reduced frequency of prolonged seizures in Dravet syndrome.

Object In this paper the authors' goal was to identify preoperative variables that predict long-term seizure freedom among patients with mesial temporal sclerosis (MTS) after single-stage anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH). Methods The authors retrospectively reviewed 116 consecutive patients (66 females, mean age at surgery 40.7 years) with refractory seizures and pathologically confirmed MTS who underwent ATL-AH with at least 2 years of follow-up. All patients underwent preoperative MRI and video-electroencephalography (EEG); 106 patients (91.4%) underwent Wada testing and 107 patients (92.2%) had neuropsychological evaluations. The authors assessed the concordance of these 4 studies (defined as test consistent with the side of eventual surgery) and analyzed the impact of preoperative variables on seizure freedom. Results The median follow-up after surgery was 6.7 years (mean 6.9 years). Overall, 103 patients (89%) were seizure free, and 109 patients (94%) had Engel Class I or II outcome. Concordant findings were highest for video-EEG (100%), PET (100%), MRI (99.0%), and Wada testing (90.4%) and lowest for SPECT (84.6%) and neuropsychological testing (82.5%). Using binary logistic regression analysis (seizure free or not) and Cox proportional hazard analysis (seizure-free survival), less disparity in the Wada memory scores between the ipsilateral and contralateral sides was associated with persistent seizures. Conclusions Seizure freedom of nearly 90% can be achieved with ATL-AH in properly selected patients with MTS and concordant preoperative studies. The low number of poor outcomes and exclusion of multistage patients limit the statistical power to determine preoperative variables that predict failure. Strong Wada memory lateralization was associated with excellent long-term outcome and adds important localization information to structural and neurophysiological data in predicting outcome after ATL-AH for MTS.

Object In patients with tuberous sclerosis complex (TSC), the tuber-to-brain proportion (TBP) is a marker of seizure severity and cognitive function. However, few studies have quantified the TBP. Furthermore, authors of these studies have measured the TBP at only a single time point, despite the fact that tuber cells were found to express proliferation markers, suggesting that they may be dynamic lesions. Authors of the present study used a semi-automated tuber segmentation program to determine whether the TBP changes over time. Methods Axial FLAIR MR images were retrospectively identified for patients with TSC who had undergone imaging at the authors' institution between February 1998 and June 2009. Using FireVoxel software, the TBP was measured for each patient at a minimum interval of 2 years. Results Twelve patients meeting the study inclusion criteria were identified. The mean TBP was 1.88% (range 0.38%-3.70%). Eight patients demonstrated minimal changes and 3 patients demonstrated small increases in TBP. The remaining patient exhibited a decrease of 1.00%, which correlated with a visible decrease in the size of 2 cerebellar lesions. Conclusions Semi-automated brain segmentation is a valuable tool in the longitudinal study of tubers. A subset of patients with TSC, particularly those with cerebellar lesions, may exhibit changes in the TBP over time.

Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders-and specifically factors predisposing these patients-are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness.

A 20-year-old man with intellectual disability and intractable multifocal epilepsy presented to a neurologist for further evaluation and management. His seizures began at 4 months, the night after his first DPT vaccine, and he continued to have frequent tonic-clonic seizures throughout his life. Several weeks after his visit, he was found facedown on the floor, dead, by his family. His autopsy was unremarkable, but genetic testing revealed a frame shift mutation in SCN1A, consistent with severe myoclonic epilepsy of infancy (Dravet syndrome).