Faculty Bibliography

It has been suggested that alerting caregivers to seizure occurrence so they can deliver post-ictal care may be an effective way to prevent sudden unexpected death in epilepsy (SUDEP). We report two cases of SUDEP referred for an expert medical-legal review for which immediate post-ictal intervention was ineffective. In both patients, prompt resuscitation procedures by medical personnel after seizures failed to prevent SUDEP. These cases demonstrate that some seizures may lead to death even with expert intervention almost immediately after the seizure occurs. It is possible that for some SUDEP cases, seizures may trigger an irreversible cascade of cardiopulmonary and cerebral changes that lead to death. Further studies in the pathophysiology of SUDEP may help identify alternative prevention strategies.

Object Tuberous sclerosis complex (TSC) can manifest with 3 principal intracranial pathological entities: cortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). The authors analyzed the location and growth of intraventricular lesions in a large cohort of patients with TSC. Methods After institutional review board protocol approval, the authors retrospectively reviewed brain MRI scans of TSC patients for whom at least 1 electronically stored cranial MRI study was available. Collected data included location, size, and growth over time of all intraventricular lesions. Results The authors reviewed 560 scans in 103 patients, who harbored 496 intraventricular lesions. Of the 496 lesions, 157 lesions were located along the caudate-thalamic groove (CTG) in 88 patients. Twenty SEGAs were operated on. The remaining 339 lesions were distributed along the lateral ventricle, always in contact with the course of the caudate nucleus, and were presumed to be SENs. Twenty-two patients with more than 4 years of follow-up had 34 lesions along the CTG, of which 23 were stable in size and 11 grew. All other intraventricular lesions were stable. Seven-Tesla MRI showed the intimate association of SENs and the caudate nucleus in 1 patient. Conclusions Intraventricular lesions in TSC patients are located throughout the lateral ventricular wall. Their location exclusively follows the course of the caudate nucleus. Only lesions along the CTG showed the potential to grow, and these were then identified as SEGAs. The remaining lesions were SENs. Understanding why these lesions develop in relation to the caudate nucleus may offer insights into therapy.

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.

INTRODUCTION: : Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme converting glutamate into gamma-aminobutyric acid. Impaired GAD function can alter motor, cognitive, and behavioral function. Anti-GAD antibodies (GADAbs) can cause several neurological disorders. However, the association between anti-GADAbs and pure psychosis, without seizures or focal neurological deficits, is not well defined. CASE REPORT: : A 19-year-old woman with recent-onset psychotic disorder was diagnosed with schizophrenia. Brain magnetic resonance imaging and cerebrospinal fluid analysis were normal. Serum anti-GADAb titers were elevated. Brain biopsy showed subcortical gliosis and microglia-macrophage infiltration. The clinical syndrome improved with immune therapy. CONCLUSIONS: : Severe psychosis and mild cognitive decline without other neurological features, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision diagnostic criteria for schizophrenia, can result from brain inflammation associated with elevated serum anti-GADAbs.

Purpose: Intracranial monitoring (IM) is a key diagnostic procedure for select patients with treatment-resistant epilepsy (TRE). Seizure focus resection may improve seizure control in both lesional and nonlesional TRE. IM itself is not considered to have therapeutic potential. We describe a cohort of patients with improved seizure control following IM without resective surgery. Methods: Over 12.5 years, 161 children underwent 496 surgeries including intracranial monitoring. We retrospectively reviewed the patients' charts, operative reports, and radiologic scans, under an institutional review board-approved protocol. Key Findings: Seventeen patients underwent only IM, without additional resective surgery, and seven had a dramatic improvement in their epilepsy; six of the seven patients are seizure-free (Engel class I), and one rarely has seizures (Engel class II). All seven patients had frequent seizures that led to IM: either daily (five patients) or 1-2 per week (two patients). The mean age (+/- standard deviation, SD) at seizure onset was 1.6 +/- 1.3 years (range 0.5-4 years). Etiologies were tuberous sclerosis (3 patients), trauma (1 patient), and unknown (3 patients). Mean age at surgery (+/- SD) was 4.1 +/- 2 years (range 1-7 years), and duration of epilepsy 2.5 +/- 1.1 years (range 0.5-4 years). Duration of IM was 11.7 +/- 5.6 days (5-19 days). Six patients had bilateral and one unilateral invasive electrodes. At last follow-up, four patients required fewer antiepileptic drugs (AEDs), one had the same medication but a higher dose, and two patients were taking additional AEDs. Follow-up was 30.6 +/- 9.5 months (range 19-41 months). Significance: Although uncommon, patients with TRE may improve after IM alone. The explanation for this observation remains unclear; however, perioperative medications including steroids, direct cortical manipulation, or other factors may influence the epileptogenic network

Depression in patients with temporal lobe epilepsy (TLE) is highly prevalent and carries significant morbidity and mortality. Its neural basis is poorly understood. We used quantitative, surface-based MRI analysis to correlate brain morphometry with severity of depressive symptoms in 38 patients with TLE and 45 controls. Increasing severity of depressive symptoms was associated with orbitofrontal cortex (OFC) thinning in controls, but with OFC thickening in TLE patients. These results demonstrate distinct neuroanatomical substrates for depression with and without TLE, and suggest a unique role for OFC, a limbic region for emotional processing strongly interconnected with medial temporal structures, in TLE-related depressive symptoms

Transmeningeal pharmacotherapy for cerebral cortical disorders requires drug delivery through the subdural/subarachnoid space, ideally with a feedback controlled mechanism. We have developed a device suitable for this function. The first novel component of the apparatus is a silicone rubber strip equipped with (a) fluid-exchange ports for both drug delivery and local cerebrospinal fluid (CSF) removal, and (b) EEG recording electrode contacts. This strip can be positioned between the dura and pia maters. The second novel component is an implantable dual minipump that directs fluid movement to and from the silicone strip and is accessible for refilling and emptying the drug and CSF reservoirs, respectively. This minipump is regulated by a battery-powered microcontroller integrating a bi-directional radiofrequency (RF) communication module. The entire apparatus was implanted in 5 macaque monkeys, with the subdural strip positioned over the frontal cortex and the minipump assembly secured to the cranium under a protective cap. The system was successfully tested for up to 8months for (1) transmeningeal drug delivery using acetylcholine (ACh) and muscimol as test compounds, (2) RF-transmission of neocortical EEG data to assess the efficacy of drug delivery, and (3) local CSF removal for subsequent diagnostic analyses. The device can be used for (a) monitoring neocortical electrophysiology and neurochemistry in freely behaving nonhuman primates for more than 6months, (b) determining the neurobiological impact of subdural/subarachnoid drug delivery interfaces, (c) obtaining novel neuropharmacological data on the effects of central nervous system (CNS) drugs, and (d) performing translational studies to develop subdural pharmacotherapy devices

Septal nuclei, components of basal forebrain, are strongly and reciprocally connected with hippocampus, and have been shown in animals to play a critical role in memory. In humans, the septal forebrain has received little attention. To examine the role of human septal forebrain in memory, we acquired high-resolution magnetic resonance imaging scans from 25 healthy subjects and calculated septal forebrain volume using recently developed probabilistic cytoarchitectonic maps. We indexed memory with the California Verbal Learning Test-II. Linear regression showed that bilateral septal forebrain volume was a significant positive predictor of recognition memory accuracy. More specifically, larger septal forebrain volume was associated with the ability to recall item source/context accuracy. Results indicate specific involvement of septal forebrain in human source memory, and recall the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases. (JINS, 2012, 18, 157-161)