Faculty Bibliography

Rationale: Magnetic resonance imaging has revolutionized the detection of small structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we used morphometric MRI to quantify imaging features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries that went undetected by routine clinical visual inspection. Methods: Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness and gray-white matter contrast (GWC). To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To establish the effectiveness of the technique, we compared the detected structural abnormalities to resection margins, seizure onset zones based on intracranial EEG and pathological features using post-resection histology. Results: We report optimal parameters by which cortical thickness and GWC features detected previously occult lesions. We present sensitivity and specificity measures for each threshold and smoothing level to allow for selection of parameters based on clinical need. Conclusions: This automated approach may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore may improve identification of patients with intractable focal epilepsy who may benefit from surgery

Rationale: Partial seizures in temporal lobe epilepsy (TLE) are classified as complex-partial, resulting in a loss of consciousness, or simple-partial, associated with preserved consciousness. The mechanistic underpinnings of impaired consciousness in partial seizures are poorly understood. Investigators have previously suggested that unconsciousness during partial seizures may be related to bilateral temporal lobe involvement, seizure onset in the language-dominant hemisphere, or increased cortico-thalamic synchrony. Earlier work has indeed shown that temporal lobe seizures are often associated with bilateral slow rhythms and decreased cerebral blood flow in the frontoparietal neocortex. Ictal neocortical slow rhythms resemble cortical activity observed during sleep or deep anesthesia. However, no prior investigations have directly examined the relationship between ictal neocortical slow activity and behavioral unresponsiveness. Methods: We analyzed intracranial electroencephalographic (EEG) recordings during 63 partial seizures in 26 TLE patients. Blinded reviewers analyzed behavioral responsiveness based on video recordings of seizures and classified consciousness as impaired (complex-partial) or unimpaired (simple-partial). Results: We found significantly elevated delta-range 1-2 Hz slow activity in the frontal and parietal neocortices during complex-partial compared to simple-partial seizures. Also, fast beta-range EEG activity in the contralateral temporal lobe, indicating seizure propagation, was significantly correlated with slow delta activity in the frontoparietal neocortex. Furthermore, we observed that seizure onset in the languagedominant hemisphere and bilateral temporal lobe involvement were more common during complex- than simple-partial seizures. Conclusions: We have proposed a 'network inhibition hypothesis' based on prior human and animal studies, in which subcortical arousal systems are disrupted by partial seizures, producing a depressed cortical state of slow activity and impaired consciousness. Our present findings illustrate that impaired consciousness is associated with ictal neocortical slow and bilateral temporal fast rhythms, raising the possibility that spread of seizure activity to bilateral temporal lobes may exert a powerful inhibitory effect on subcortical arousal networks. Further investigations are necessary to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction, and may ultimately lead to specific treatments targeted at preventing this negative consequence of TLE

OBJECTIVE: Studies have reported improved seizure control with increased duration of vagus nerve stimulation (VNS) but are prone to methodological biases. We analyzed the efficacy of VNS over time in patients with treatment-resistant epilepsy (TRE) who underwent VNS therapy 10 or more years. METHODS: We retrospectively reviewed 65 consecutive patients (29 females) who underwent VNS therapy >/=10years. The mean age at VNS insertion was 30.0years. Forty-four adults (>/=18years; 67.7%) and 21 children (32.3%) were included. Seizure frequency and antiepileptic drug (AED) regimens were recorded prior to VNS and, following VNS insertion, at 6months, 1year, 2years, and every 2years thereafter. RESULTS: The mean duration of VNS therapy for this group was 10.4years, and the mean decrease in seizure frequency at last follow-up was 76.3%. The mean reduction in seizures at 6months and years 1, 2, 4, 6, 8, and 10years was 35.7, 52.1, 58.3, 60.4, 65.7, 75.5, and 75.5%, respectively. Seizure frequency was significantly reduced from baseline at each of the recorded intervals (P<0.001). There was a trend toward increased AED burden in the latter years of the follow-up period. CONCLUSION: Following a 'ramp-up' and accommodation period throughout the initial 24months after VNS implantation, seizure control improved slightly over the subsequent years of therapy and eventually stabilized. Variation in seizure frequency, however, was common, and frequent changes in AED regimens or stimulation parameters were likely an important and possibly synergistic component of seizure control

Parents of children with tuberous sclerosis complex who underwent multistage resections for treatment of refractory seizures were offered a telephone questionnaire regarding quality of life (QOL) of child and family since surgery. Of 53 families, 39 responded. Age at epilepsy onset was birth to 3months. Average duration of epilepsy before the first surgery was 5.1years, and average age at surgery was 5.8. The average follow-up was 3.9. Seventy-seven percent had a >90% reduction in disabling seizures. In all outcome categories, 46-85% had at least a moderate improvement in QOL. There was a significant correlation between QOL variables and Engel outcome class. Despite the potential burden posed by the aggressive surgical approach, including multiple surgeries and long hospitalization periods, 94% of parents would choose the same course once again. We conclude that aggressive surgical treatment of tuberous sclerosis complex-related refractory seizures is associated with significant control of epilepsy as well as improved QOL for the patient and family

People with epilepsy have a higher risk for suicide than people without epilepsy. The relationship between seizure control and suicide is controversial. A standardized protocol to record history, diagnostic testing, and neuropsychiatric assessments was administered. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered presurgically and yearly for up to 5 years. Among the 396 enrolled, 4 of 27 deaths were attributed to suicide. The standardized mortality ratio, compared with suicides in the U.S. population and adjusted for age and gender, was 13.3 (95% CI=3.6-34.0). Only one patient had a BDI score suggestive of severe depression (BDI=33), one had depressive symptoms that did not the meet the depressive range (BDI=7), and the other two reported no depressive symptoms. Two of the patients reported moderate to severe anxiety symptoms (BAI=17 and 21, respectively). Suicide may occur after epilepsy surgery, even when patients report excellent seizure control

OBJECTIVE: The goal of this study was to assess the efficacy and safety of vagus nerve stimulation in a consecutive series of adults and children with treatment-resistant epilepsy (TRE). METHODS: In this retrospective review of a prospectively created database of 436 consecutive patients who underwent vagus nerve stimulator implantation for TRE between November 1997 and April 2008, there were 220 (50.5%) females and 216 (49.5%) males ranging in age from 1 to 76years at the time of implantation (mean: 29.0+/-16.5). Thirty-three patients (7.6%) in the primary implantation group had inadequate follow-up (<3months from implantation) and three patients had early device removal because of infection and were excluded from seizure control outcome analyses. RESULTS: Duration of vagus nerve stimulation treatment varied from 10days to 11years (mean: 4.94years). Mean seizure frequency significantly improved following implantation (mean reduction: 55.8%, P<0.0001). Seizure control >/=90% was achieved in 90 patients (22.5%), >/=75% seizure control in 162 patients (40.5%), >/=50% improvement in 255 patients (63.75%), and <50% improvement in 145 patients (36.25%). Permanent injury to the vagus nerve occurred in 2.8% of patients. CONCLUSION: Vagus nerve stimulation is a safe and effective palliative treatment option for focal and generalized TRE in adults and children. When used in conjunction with a multidisciplinary and multimodality treatment regimen including aggressive antiepileptic drug regimens and epilepsy surgery when appropriate, more than 60% of patients with TRE experienced at least a 50% reduction in seizure burden. Good results were seen in patients with non-U.S. Food and Drug Administration-approved indications. Prospective, randomized trials are needed for patients with generalized epilepsies and for younger children to potentially expand the number of patients who may benefit from this palliative treatment

Purpose: Epilepsy and electroencephalographic abnormalities are frequent in idiopathic autism, but there is little information regarding treatment-resistant epilepsy (TRE) in this group. We sought to define the clinical and electrophysiologic characteristics and treatment outcomes in these patients. Methods: We retrospectively reviewed clinical and laboratory data of patients with idiopathic autism evaluated at NYU Epilepsy Center during a 20-year period. Key Findings: One hundred twenty-seven patients had idiopathic autism and at least one epileptic seizure; 33.9% had TRE and 27.5% were seizure free. The remaining 38.6% of patients had infrequent seizures or insufficient data to categorize. Patients with TRE had a significantly earlier onset of seizures than seizure-free patients, and a trend for more developmental regression and motor and language delays. Three patients had surgical resection (two had limited improvement and one had no improvement) and one had an anterior callosotomy (no improvement). Vagus nerve stimulator (VNS) implantation provided limited improvement (2 patients) and no improvement (7). Significance: This study found that TRE is common in idiopathic autism and more common with early age of seizure onset. Relatively few patients underwent surgical resection due to multifocal partial epilepsy, comorbid generalized epilepsy, or limited impact of ongoing partial seizures given other problems related to autism. Our small sample suggests that surgical and VNS outcomes in this group are less favorable than in other TRE populations

Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries. Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness, gray-white matter contrast, local gyrification, sulcal depth, jacobian distance and curvature. To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To test the effectiveness of the technique to detect lesions of epileptogenic character, we compared the detected structural abnormalities to expert-tracings, intracranial EEG, pathology and surgical outcome in a homogeneous patient sample. With optimal parameters and by combining thickness and GWC, the surface-based detection method identified 92% of cortical lesions (sensitivity) with few false positives (96% specificity), successfully discriminating patients from controls 94% of the time. The detected structural abnormalities were related to the seizure onset zones, abnormal histology and positive outcome in all surgical patients. However, the method failed to adequately describe lesion extent in most cases. Automated surface-based MRI morphometry, if used with optimized parameters, may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore could improve identification of patients with intractable focal epilepsy who may benefit from surgery

Psychogenic nonepileptic seizures (PNES) resemble epileptic seizures and are often misdiagnosed and mistreated as the latter. Occasionally, epileptic seizures are misdiagnosed and mistreated as PNES. 70% of PNES cases develop between the second and fourth decades of life, but this disease can also affect children and the elderly. At least 10% of patients with PNES have concurrent epileptic seizures or have had epileptic seizures before being diagnosed with PNES. Psychological stress exceeding an individual's coping capacity often precedes PNES. Clinicians can find differentiating between PNES and epileptic seizures challenging. Some clinical features can help distinguish PNES from epileptic seizures, but other features associated with PNES are nonspecific and occur during both types of seizures. Diagnostic errors often result from an overreliance on specific clinical features. Note that no single feature is pathognomonic for PNES. When typical seizures can be recorded, video-EEG is the diagnostic gold standard for PNES, and in such cases a diagnosis can be made with high accuracy. When video-EEG reveals no epileptiform activity before, during or after the ictus, thorough neurological and psychiatric histories can be used to confirm the diagnosis of PNES. In this article, we review the clinical features that can help clinicians differentiate between PNES and epileptic seizures

Nonparaneoplastic glutamic acid decarboxylase antibody (GADAb)-related autoimmune encephalitis is a syndrome characterized by refractory seizures, progressive cognitive deficits, and psychiatric manifestations. The limbic subtype is well described, has characteristic affective and memory disturbances, and typical mesial temporal MRI abnormalities. We found only one single case report of the extralimbic subtype. We report clinical, radiological, and pathological findings of two additional cases with contrast-enhancing lesions. One of our cases presented as vasculitis, and the other imitated a tumor. Pathological evidence of both vasculitis and encephalitis has never been previously reported in any inflammatory condition affecting the brain. Our cases confirm prior reports that immune therapy can better control seizures associated with GADAb autoimmune encephalitis, and support the rationale for assaying for GADAb titers in patients with etiologically unclear extralimbic lesions and refractory epilepsy, independent of seizure types