Faculty Bibliography

Functional neuroimaging implicates hyperactivity of amygdala-orbitofrontal circuitry as a common neurobiological mechanism underlying the development of anxiety. Less is known about anxiety-related structural differences in this network. In this study, a sample of healthy adults with no history of anxiety disorders completed a 3T MRI scan and self-report mood inventories. Post-processing quantitative MRI image analysis included segmentation and volume estimation of subcortical structures, which were regressed on anxiety inventory scores, with depression scores used to establish discriminant validity. We then used a quantitative vertex-based post-processing method to correlate (1) anxiety scores and (2) left amygdala volumes with cortical thickness across the whole cortical mantle. Left amygdala volumes predicted anxiety, with decreased amygdala volume associated with higher anxiety on both state and trait anxiety measures. A negative correlation between left amygdala volume and cortical thickness overlapped with a positive correlation between anxiety and cortical thickness in left lateral orbitofrontal cortex. These results suggest a structural anxiety network that corresponds with a large body of evidence from functional neuroimaging. Such findings raise the possibility that structural abnormalities may result in a greater vulnerability to anxiety or conversely that elevated anxiety symptoms may result in focal structural changes

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

Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and muscimol pretreatment in the concentration range of 0.005-0.05mM did not prevent EEG seizures. In contrast, 0.5-mM muscimol reduced the average EEG Seizure Duration Ratio value from 0.30+/-0.04 to 0. At this muscimol concentration, the average baseline multineuronal firing rate of 10.9+/-4.4spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0+/-1.8 to 3.7+/-0.9spikes/s in the last 10min of pretreatment. These data indicate that transmeningeal muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions

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

OBJECTIVE: We describe a patient with seronegative autoimmune limbic encephalitis (SNALE) masquerading as glioma. Brain magnetic resonance imaging (MRI) abnormalities, distinctive pathological findings, and spontaneous remission are highlighted. BACKGROUND: There are 15 previously reported SNALE cases, 1 with pathology. MATERIALS AND METHODS: A 66-year-old man presented with prominent amnestic syndrome, progressive cognitive decline, and refractory complex partial seizures. RESULTS: Initial brain MRI suggested herpes limbic encephalitis. A 3-week course of intravenous acyclovir was ineffective. Cerebrospinal fluid analysis revealed no pleocytosis. Repeat brain MRI showed a left uncal-hippocampal, contrast-enhancing lesion with mass effect, which was resected. Pathology revealed perivascular and parenchymal mixed lymphocytic inflammatory infiltrates, microglial nodules, neuronophagia, microglial activation, astrocytosis, and lymphocyte emperipolesis within neurons. Thorough searches for infectious pathogens and autoantibodies were negative. Six weeks later, a new enhancing right mesial temporal lesion appeared, with increased seizure activity and further cognitive impairment. Although immune therapy was declined, spontaneous resolution of the new enhancing lesion, with full seizure control and significant cognitive improvement, occurred. CONCLUSIONS: SNALE may masquerade as glioma. Pathologic changes in our case of SNALE are distinctive. Spontaneous resolution of a focal SNALE lesion may potentially occur without immune therapy

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

BACKGROUND: : Experimental and clinical studies support a pathogenic role of microglial activation and proliferation (MAP) in epileptogenesis. METHODS: : From a consecutive series of 319 surgically treated epilepsy cases, we retrospectively reviewed the histopathological sections of 92 cases to define the prevalence and severity of MAP after excluding the other 227 because of coexisting disorders that might contribute to MAP. Severity of MAP was compared with underlying abnormalities. We assessed the response to intravenous immunoglobulin and plasmapheresis in one patient with severe MAP who had failed multiple antiepileptic drugs and epilepsy surgery. RESULTS: : MAP was detected with routine (hematoxylin and eosin) stain in 46 of 92 cases (50%). MAP was mild in 32 cases (69.6%), moderate in 12 (26.1%), and severe in 2 (4.3%). The prevalence and severity of MAP were independent of underlying abnormalities. Immunomodulatory therapy was followed by a greater than 90% reduction in seizure activity in the treated patient. CONCLUSION: : MAP is prevalent in resected human epilepsy tissue. Failure to down-regulate MAP contributes to chronic neuronal hyperexcitability. We hypothesize that MAP initiates a cycle of inflammation-induced seizures and seizure-induced inflammation. Microglia-driven epilepsy may be a primary pathogenic process in a small number of cases, as suggested by the pathology and therapeutic response in our patient, but may contribute to epileptogenesis in many more

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

'If I wished to show a student the difficulties of getting at truth from medical experience, I would give him the history of epilepsy to read.' Oliver Wendell Holmes (1)If the medical experience of epilepsy is obscured by uncertainties, then its classification is mired in the mud of expert opinion. The newly revised terms and concepts for 'organizing' (also known as 'classifying') seizures and epilepsy provide a humble and modern perspective, with many superb suggestions (2). The central points are well articulated and valid: 1) divorcing classification from 'expert opinion' and marrying it to science; 2) acknowledging what is unknown; and 3) simplifying and clarifying terminology. Yet, the revision lacks the crisp clarity needed to educate students, patients, and colleagues. And some recommendations lack a clear scientific or semantic basis

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