David Trejo

Electrical stimulation of the hippocampal epileptic foci for seizure control: a double-blind, long-term follow-up study.

Summary:  Purpose: Our aim was to evaluate the safety and efficacy of electrical stimulation of the hippocampus in a long‐term follow‐up study, as well as its impact on memory performance in the treatment of patients with refractory mesial temporal lobe epilepsy.

Preliminary Study in Patients With Obsessive-Compulsive Disorder Treated With Electrical Stimulation in the Inferior Thalamic Peduncle

OBJECTIVE Deep brain stimulation has been used in the treatment of refractory obsessive-compulsive disorder (OCD). Our principal objective was to determine the safety and effectiveness of deep brain stimulation of the inferior thalamic peduncle in the treatment of refractory OCD. METHODS An open protocol was performed from March 2003 to April 2007 in 5 patients with OCD refractory to conventional treatments. Bilateral stereotactic implantation of tetrapolar electrodes was aimed at the inferior thalamic peduncle and corroborated by electrophysiological responses and magnetic resonance imaging. All patients were off stimulation for 1 month after implantation. In the on-stimulation period, parameters were set at 5 V, 450 microseconds, 130 Hz in bipolar and continuous mode. Clinical changes were evaluated every 3 months for 12 months by means of the Yale-Brown Obsessive Compulsive Scale and the Global Assessment of Functioning scale. Statistical significance was assessed by the Friedman and Wilcoxon tests. RESULTS The mean Yale-Brown Obsessive Compulsive Scale score decreased from 35 to 17.8 (P < 0.001), and the mean Global Assessment of Functioning scale score improved from 20% to 70% (P < 0.0001). The neuropsychological battery did not show significant changes, and there were no side effects related to electrical stimulation in the chronic period. CONCLUSION We conclude that inferior thalamic peduncle stimulation is a safe procedure and may be an effective alternative in the treatment of those OCD cases refractory to conventional treatments.

NEUROMODULATION OF EPILEPTIC FOCI IN PATIENTS WITH NON-LESIONAL REFRACTORY MOTOR EPILEPSY

We report two cases of chronic therapeutic stimulation of epileptic foci localized in motor areas. Case 1 is an adolescent with supplementary motor area seizures whose intracranial recordings showed a right SMA focus. Case 2 is a female teenager with primary motor seizures originating in the right motor cortex in the hand area as shown by her intracranial recordings and cortical mapping. Both had apparently normal MRI. Chronic stimulation of the epileptic focus decreased the number of seizures more than 90% the seizure number while preserving motor function. None of the patients had side effects. Neuromodulation is proposed as a safe, efficient surgical alternative for motor seizure control.

Alterations of 5-HT1A receptor-induced G-protein functional activation and relationship to memory deficits in patients with pharmacoresistant temporal lobe epilepsy

The 5-hydroxytryptamine-1A (5-HT1A) receptors are known to be involved in the inhibition of seizures in epilepsy. Moreover, studies propose a role for the 5-HT1A receptor in memory function; it is believed that the higher density of this receptor in the hippocampus plays an important role in its regulation. Positron emission tomography (PET) studies in patients with mesial temporal lobe epilepsy (mTLE) have demonstrated that a decrease in 5-HT1A receptor binding in temporal regions may play a role in memory impairment. The evidences lead us to speculate whether this decrease in receptor binding is associated with a reduced receptor number or if the functionality of the 5-HT1A receptor-induced G-protein activation and/or the second messenger cascade is modified. The purpose of the present study is to determine 5-HT1A receptor-induced G-protein functional activation by 8-OH-DPAT-stimulated [(35)S]GTPγS binding assay in hippocampal tissue of surgical patients with mTLE. We correlate functional activity with epilepsy history and neuropsychological assessment of memory. We found that maximum functional activation stimulation values (Emax) of [(35)S]GTPγS binding were significantly increased in mTLE group when compared to autopsy samples. Furthermore, significant correlations were found: (1) positive coefficients between the Emax with the age of patient and frequency of seizures; (2) negative coefficients between the Emax and working memory, immediate recall and delayed recall memory tasks. Our data suggest that the epileptic hippocampus of patients with mTLE presents an increase in 5-HT1A receptor-induced G-protein functional activation, and that this altered activity is related to age and seizure frequency, as well as to memory consolidation deficit.

Neuromodulation du système nerveux central dans le traitement des épilepsies: I-Éfficacité et sécurité de la méthode☆

We present here a review of the work on neuromodulation - defined as application of an inhibitory or excitatory current - on intracranial structures for the treatment of drug-resistant epilepsy. Near 250 patients were treated using a neuromodulation technique of the cerebellum (paravermian cortex), the CM-pf nucleus of the thalamus, the hippocampus, epileptogenic foci, and anterior ventral nucleus of the thalamus, with a one- to 15-year follow-up. Four contact strips were used for cerebellar and functional region neuromodulation, and DBS-type depth electrodes were stereotactically implanted for CM-pf and anterior nuclei of the thalamus and hippocampal neuromodulation. Electric stimulation was cyclic in almost all trials, using low frequency (10-40 Hz) for excitation and high frequency (60-185 Hz) for inhibition. Seizure frequency reduction was variable, depending on the neuromodulation site and patient selection, although seizure duration decreased in most patients. Cerebellar neuromodulation was followed by a 78% reduction in tonic and tonic-clonic seizures, CM-pf neuromodulation by an 83% reduction in tonic-clonic seizures and atypical absence of Lennox-Gastaut syndrome, with a 17.2% seizure-free and drug-free patient rate. Hippocampal neuromodulation was followed by a 73% reduction in partial complex seizures, with a 33% seizure-free patient rate. Anterior ventral nucleus of the thalamus was followed by a 63% reduction in tonic-clonic, tonic and atonic seizures. Several prognostic factors were identified in order to improve future results. There was no mortality and morbidity was limited to skin erosion at the neurostimulator site. Seizure reduction was associated with improved neuropsychological performance and better quality of life. Neuromodulation is safe and effective for the treatment of epileptic seizures of various origins. Several targets may be associated in a single patient, especially when bilateral hippocampal seizure foci are present.

Central nervous system neuromodulation for the treatment of epilepsy

We present here a review of the work on neuromodulation - defined as application of an inhibitory or excitatory current - on intracranial structures for the treatment of drug-resistant epilepsy. Near 250 patients were treated using a neuromodulation technique of the cerebellum (paravermian cortex), the CM-pf nucleus of the thalamus, the hippocampus, epileptogenic foci, and anterior ventral nucleus of the thalamus, with a one- to 15-year follow-up. Four contact strips were used for cerebellar and functional region neuromodulation, and DBS-type depth electrodes were stereotactically implanted for CM-pf and anterior nuclei of the thalamus and hippocampal neuromodulation. Electric stimulation was cyclic in almost all trials, using low frequency (10-40 Hz) for excitation and high frequency (60-185 Hz) for inhibition. Seizure frequency reduction was variable, depending on the neuromodulation site and patient selection, although seizure duration decreased in most patients. Cerebellar neuromodulation was followed by a 78% reduction in tonic and tonic-clonic seizures, CM-pf neuromodulation by an 83% reduction in tonic-clonic seizures and atypical absence of Lennox-Gastaut syndrome, with a 17.2% seizure-free and drug-free patient rate. Hippocampal neuromodulation was followed by a 73% reduction in partial complex seizures, with a 33% seizure-free patient rate. Anterior ventral nucleus of the thalamus was followed by a 63% reduction in tonic-clonic, tonic and atonic seizures. Several prognostic factors were identified in order to improve future results. There was no mortality and morbidity was limited to skin erosion at the neurostimulator site. Seizure reduction was associated with improved neuropsychological performance and better quality of life. Neuromodulation is safe and effective for the treatment of epileptic seizures of various origins. Several targets may be associated in a single patient, especially when bilateral hippocampal seizure foci are present.

Memory for facial expressions in patients with temporal lobe epilepsy: preliminary findings

Abstract Temporal Lobe Epilepsy (TLE) is associated with memory and emotional impairments. However, the majority of previous studies examined patients after the affected structures (hippocampus and amygdala) were surgically removed, so it remains unclear to what extent these deficits are associated with the illness itself or are a consequence of the surgery. Thus, the objective of this study was to compare recognition memory for facial emotional expressions in pre- and post-surgery TLE patients, and its relationship to neuropsychological and clinical variables. We observed higher memory accuracy in pre-surgical patients than in those who had undergone surgery. Moreover, there was a significant positive correlation between the task and the executive functions and memory subtests of the neuropsychological battery, as well as a negative correlation with illness duration. These preliminary results suggest a possible effect of the surgical resection on memory, and highlight the importance of an early intervention for reducing cognitive decline.

Neuromodulation du système nerveux central dans le traitement des épilepsies

We present here a review of the work on neuromodulation - defined as application of an inhibitory or excitatory current - on intracranial structures for the treatment of drug-resistant epilepsy. Near 250 patients were treated using a neuromodulation technique of the cerebellum (paravermian cortex), the CM-pf nucleus of the thalamus, the hippocampus, epileptogenic foci, and anterior ventral nucleus of the thalamus, with a one- to 15-year follow-up. Four contact strips were used for cerebellar and functional region neuromodulation, and DBS-type depth electrodes were stereotactically implanted for CM-pf and anterior nuclei of the thalamus and hippocampal neuromodulation. Electric stimulation was cyclic in almost all trials, using low frequency (10-40 Hz) for excitation and high frequency (60-185 Hz) for inhibition. Seizure frequency reduction was variable, depending on the neuromodulation site and patient selection, although seizure duration decreased in most patients. Cerebellar neuromodulation was followed by a 78% reduction in tonic and tonic-clonic seizures, CM-pf neuromodulation by an 83% reduction in tonic-clonic seizures and atypical absence of Lennox-Gastaut syndrome, with a 17.2% seizure-free and drug-free patient rate. Hippocampal neuromodulation was followed by a 73% reduction in partial complex seizures, with a 33% seizure-free patient rate. Anterior ventral nucleus of the thalamus was followed by a 63% reduction in tonic-clonic, tonic and atonic seizures. Several prognostic factors were identified in order to improve future results. There was no mortality and morbidity was limited to skin erosion at the neurostimulator site. Seizure reduction was associated with improved neuropsychological performance and better quality of life. Neuromodulation is safe and effective for the treatment of epileptic seizures of various origins. Several targets may be associated in a single patient, especially when bilateral hippocampal seizure foci are present.