Jeremy D. Slater

Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures

Electrical stimulation of the vagus nerve (VNS) is a new method for the treatment of patients with medically intractable epilepsy. Sixteen patients, ten of whom participated in a larger multicenter double-blind trial on the efficacy of VNS in epilepsy, and six who participated in pilot studies, consented to participate in the present study. Ten patients received HIGH stimulation and six patients LOW stimulation for the 3-month trial. Cerebrospinal fluid (CSF) samples (16 ml) were collected both before and after 3 months of VNS. Amino acid and neurotransmitter metabolites were analyzed. Four patients responded to VS with more than a 25% seizure reduction after 3 months. Mean and median concentrations of phosphoethanolamine (PEA) increased in responders and decreased in nonresponders. Free GABA increased in both groups but more so in the nonresponders. After 9 months of VS (6-9 months on HIGH stimulation) 4 of 15 patients had more than 40% seizure reduction. There were significant correlations between seizure reduction and increases in asparagine, phenylalanine, PEA, alanine and tryptophan concentrations. Comparison between patients with HIGH or LOW stimulation showed a significant increase in ethanolamine (EA) in the HIGH group and a decrease in glutamine in the LOW group. All patients regardless of response or stimulation intensity showed significantly increased total and free GABA levels. A decrease in CSF aspartate was marginally significant. Other trends were decreases in glutamate and increases in 5-hydroxyindoleacetic acid. Chronic VNS appears to have an effect on various amino acids pools in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereotactic laser ablation of epileptogenic periventricular nodular heterotopia

Periventricular nodular heterotopia (PVNH) is a neuronal migrational disorder often associated with pharmacoresistant epilepsy (PRE). Resective surgery for PVNH is limited by its deep location, and the overlying eloquent cortex or white matter. Stereotactic MR guided laser interstitial thermal therapy (MRgLITT) has recently become available for controlled focal ablation, enabling us to target these lesions. We here demonstrate the novel application and techniques for the use of MRgLITT in the management of PVNH epilepsy. Comprehensive presurgical evaluation, including intracranial EEG monitoring in two patients revealed the PVNH to be crucially involved in their PRE. We used MRgLITT to maximally ablate the PVNH in both cases. In the first case, seizure medication adjustment coupled with PVNH ablation, and in the second, PVNH ablation in addition to temporal lobectomy rendered the patient seizure free. A transient visual deficit occurred following ablation in the second patient. MRgLITT is a promising minimally invasive technique for ablation of epileptogenic PVNH, a disease not generally viewed as surgically treatable epilepsy. We also show here the feasibility of applying this technique through multiple trajectories and to create lesions of complex shapes. The broad applicability and long term efficacy of MRgLITT need to be elaborated further.

Induction of Pseudoseizures with Intravenous Saline Placebo

Summary: For a 2‐year period, all patients admitted to the inpatient adult EEG videotelemetry unit of the University of Miami School of Medicine underwent attempted event induction with intravenous normal saline placebo. Of 175 patients monitored during that period, 101 underwent attempted placebo saline induction, whereas 58 patients were either in the pediatric age group, were undergoing a repeat hospitalization (i.e., depth electrode monitoring), or refused induction. The final diagnosis in each patient was established after re‐view of the history; physical, interictal, and ictal EEG findings; brain imaging studies; interictal and postictal brain single photon emission computed tomography (SPECT) and serum prolactin levels; psychiatric and psychological evaluations; and detailed neuropsychological testing. Final diagnoses were separated into epilepsy alone, pseudoseizures, epilepsy and pseudoseizures, and other (neither epilepsy nor pseudoseizures). No patient with an eventual diagnosis of epilepsy alone was inducible. Forty‐one patients with a diagnosis of epilepsy were not inducible. Of 32 patients with an eventual diagnosis of pseudoseizures, 29 were inducible. One of these 29 was also diagnosed with epilepsy. Three patients with aneventual diagnosis of pseudoseizures were not inducible; 90.6% of patients with an eventual diagnosis of pseudoseizures were inducible, i.e., had events identical to those reported by history, after injection of saline placebo. Placebo saline injection is a safe and effective means of distinguishing epilepsy from pseudoseizures.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Brocas area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Corpus Callosotomy for Seizures Associated with Band Heterotopia

Summary: Band heterotopia is a severe form of neuronal migration disorder associated with intractable epilepsy and neurologic impairment. Surgical treatment of seizures associated with this malformation has not been reported previously. We report a patient with band heterotopia and poorly controlled atonic seizures causing falls and injury. The patient was treated with anterior corpus callosotomy, with significant postoperative decrease in seizure frequency. Corpus callosotomy is a reasonable alternative to consider in management of patients with cortical heterotopia and intractable seizures.

Effects of Antiepileptic Drugs on Hormones

Summary: : A hormone is an intrinsic substance carried via the blood to a target organ which is then functionally stimulated. Similar to extrinsically administered medications, the metabolism and function of the hormones may be altered by antiepileptic drugs (AEDs). The proposed mechanisms are (a) enhanced metabolism (natural steroids, synthetic steroids, e.g., decadron and birth control pills, thyroxine, and vitamin D3), (b) altered protein bonding (thyroxine, sex hormones), (c) impaired release into the systemic circulation (calcitonin, insulin, vitamin K clotting factors) and (d) altered end‐organ effect. The AEDs most likely to interact with hormones are barbiturates, carbamazepine, and phenytoin.

Efficacy and safety of valproic acid versus phenytoin as sole therapy for newly diagnosed primary generalized tonic-clonic seizures

Treatment with antiepileptic drugs is recommended for patients who have had two unprovoked tonic-clonic seizures because data from epidemiologic studies suggest that a third seizure is likely to occur. Phenytoin has been the most commonly prescribed agent for several decades; since it was introduced in the late 1970s, valproic acid (valproate) has been reported to be effective for primary generally tonic-clonic seizures. We designed a multicenter study to compare the efficacy and safety of valproate and phenytoin as sole therapeutic agents for the treatment of patients with newly diagnosed primary generalized tonic-clonic seizures. Patients were randomized in a 2:1 ratio to valproate (n = 86) or phenytoin (n = 50); the investigation was an open-label study. Patients were followed for 6 months. After a 4-week titration period, median serum concentrations were 68.1 ± 3.1 mg/ml for valproate and 10.3 ± 0.9 mg/ml for phenytoin. The 6-month recurrence rates for generalized tonic-clonic seizures were 36 ± 6% for valproatetreated patients and 46 ± 8% for phenytoin-treated patients ( p = 0.473). Overall, the data indicated no significant differences in the efficacy or safety of valproate and phenytoin in the treatment of primary generalized tonic-clonic seizures.

Neural network analysis of the P300 event-related potential in multiple sclerosis.

Neural network analysis is sensitive to subtle changes in patterns of data. We hypothesized that a disease process which can cause impairment of cortical function such as multiple sclerosis (MS) would affect the P300 cognitive evoked potential (P300) in a manner detectable by a feedforward backpropagation neural network. Such a network was trained using a learning data set consisting of 101 P300 wave forms (from 26 MS patients and 26 normal controls). The network was then used to classify a randomly selected test data set of 20 studies (2 studies each of 5 MS patients and 5 controls) to which it had not been previously exposed, with an average accuracy (MS = abnormal, control = normal) of 81% for a single midline electrode, increasing to 90% using 3 midline electrodes in a jury system. Neural network analysis can be of help in distinguishing normal (control) P300 from abnormal (MS) P300.

A neural network design for event-related potential diagnosis

Many diseases resulting in neuropsychological impairment show abnormalities by EEG (electroencephalogram) tests. However, EEG analysis is complicated by a wide spectrum of normal patterns. Cerebral evoked potentials are stimulus-induced, averaged EEG potentials that have been found useful in patients with dementing illness. A recent report using the P300 auditory evoked potential shows that simple latency and waveform criteria result in classification accuracy of 65% for multiple sclerosis (MS) patients versus 91% for control subjects. Analysis on the same data set was performed using an artificial neural network (ANN) and a nearest neighbor (NN) classifier. An ANN classifier demonstrated a classification accuracy of 75% versus 87% on MS and control subject groups. Thus prediction accuracy was improved on average, compared with that obtained by NN classifiers or P300 statistical analysis. The classification strategy discovered by a trained ANN was analyzed by a weight pattern analysis method and compared with the P300 latency criteria.

Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance - The U.S. E-37 Trial

The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3‐5‐day Epilepsy Monitoring Unit (EMU) stay and long‐ term clinical outcomes of the device stimulating in all modes.