Marcos Velasco

Subacute electrical stimulation of the hippocampus blocks intractable temporal lobe seizures and paroxysmal EEG activities.

Summary: Purpose: To investigate the clinical, electroen‐cephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyms (SAHCS) on 10 patients with intractable temporal lobe seizures.

A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle

OBJECTIVE AND IMPORTANCE: The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD). CLINICAL PRESENTATION: This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient’s symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD. INTERVENTION: The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20. CONCLUSION: Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.

Electrical stimulation of the centromedian thalamic nucleus in the treatment of convulsive seizures: a preliminary report.

Summary: Five patients with clinical and EEG primary generalized or multifocal uncontrollable seizures underwent stereotaxic implantation of electrodes in both centromedian thalamic nuclei (CM). Each electrode consisted of a semiflexible array of three platinum‐iridium wires, isolated except at their tips, which were separated by 4 mm. Bipolar, biphasic rectangular pulses were delivered in trains of 1 min every 5 min, alternating right and left side for sessions 2 h/day. Patients were followed for 3 months with charting of clinical seizures, daily 4‐h EEG recordings from scalp and depth for 5 days and weekly thereafter. Baseline and 3‐month evaluation of psychological performance through selected Beta R, Wechsler memory scale, visual discrimination, MMPI, and Zungs rated depression scale. Tests were evaluated for significant changes by the parametric students / test and Mann Whitney nonparametric test. Clinical seizures were significantly reduced by electrical stimulation (ES), as were EEG interictal spikes and EEG slow waves. Psychological performance improved beyond that expected by reduction in seizure activity. ESCM induced a local after‐discharge (AD) that progressively developed in time and intensity, and the beneficial effects outlasted ES for periods of weeks to months, suggesting that a state of hy‐perexcitability of stimulated tissue, similar to “kindling,” was created by chronic ES.

Electrical stimulation of the centromedian thalamic nucleus in control of seizures : long-term studies

Summary: Five patients with chronic incapacitating seizures averaging 15–5,000/month were selected for study. All patients had more than one seizure type and had received maximal doses of antiepileptic drugs (AEDs). The centromedian thalamic nucleus (CM) was stimulated electrically through bilateral multicontact platinum electrodes stereotaxically placed in CM and connected to internalized pulse generators. Electrophysiologic confirmation of electrode position included thalamically elicited recruiting responses and EEG desynchronization recorded at the scalp. Stimulation parameters were adjusted individually in the range of 450–800‐μA intensity, 65 pps, 0.09 ms, in 1‐min trains, alternating right and left side stimulation and with 4‐min intervals delivered for 2 h/day. Quantitative evaluation included frequency of seizures/month, number of maximal interictal paroxysmal discharges, and frequency of background activities counted in selected scalp EEG samples, taken throughout the observation period (7–33 months). Significance of changes was evaluated by parametric Students t test. Generalized tonic‐clonic seizures (GTC) decreased dramatically, almost disappearing in all cases (p < 0.001), with a significant reduction in interictal paroxysmal discharges (p < 0.01) and a tendency toward an increase in EEG back‐ground frequency. Other generalized seizures (atypical absences) decreased significantly, but there was no change in the number of complex partial seizures (CPS). CM stimulation is useful in control of GTC, but its beneficial effect on other seizure types has not been established.

Subacute and Chronic Electrical Stimulation of the Hippocampus on Intractable Temporal Lobe Seizures: Preliminary Report

Recent animal experiments show that the application of an electrical stimulus to the amygdala or hippocampus following the kindling stimulus produced a significant and long-lasting suppressive effect on this experimental model of epilepsy. This is a preliminary report on the development of a surgical neuromodulatory procedure by chronic electrical stimulation of the hippocampus (CHCS) for control of intractable temporal lobe seizures in patients in whom anterior temporal lobectomy is not advisable, i.e., patients with bilateral temporal foci or a unilateral focus spreading to surrounding cerebral regions of the dominant hemisphere. This work was divided in two main consecutive stages. In the first stage, we demonstrated that subacute hippocampal stimulation (SAHCS) blocks intractable temporal lobe epileptogenesis with no additional damage to the stimulated tissue, and in a second stage, we attempt to demonstrate that CHCS may produce a sustained, long-lasting antiepileptic condition without additional undesirable effects on language and memory. In addition, taking advantage of this unique and ethically permissible situation, we attempt to determine whether or not the antiepileptic effects of SAHCS and CHCS are due to inhibition of the stimulation of hippocampal tissue by means of a number of electrophysiological, single photon computed tomography (SPECT) perfusion, and autoradiographic techniques.SAHCS during 3-4 weeks prior to anterior temporal lobectomy applied to a critical area located either at the anterior Pes hippocampus close to the amygdala or at the parahippocampal gyrus close to the entorhinal cortex abolished clinical seizures and significantly decreased the number of interictal spikes at focus after 5-6 days. Microscopy analysis of the stimulated tissue showed no evident histopathological differences between stimulated vs. non-stimulated hippocampal tissues. Additionally, CHCS persistently blocked temporal lobe epileptogenesis for 3-4 months with no apparent additional undesirable effects on short memory. Also, inhibition of the stimulated hippocampus seems to be one of the possible mechanisms underlying the beneficial antiepileptic effects of SAHCS and CHCS. This was revealed by increased threshold and decreased duration of the afterdischarges induced by hippocampal stimulation, flattening of the hippocampal-evoked response recovery cycles, SPECT hypoperfusion of the hippocampal region, and increased hippocampal benzodiazepine receptor binding. Future studies increasing the number and time of follow-up of patients under hippocampal stimulation are necessary before considering CHCS a reliable procedure for controlling intractable temporal lobe seizures.

Centromedian-thalamic and hippocampal electrical stimulation for the control of intractable epileptic seizures.

Summary The following two different modulatory procedures to control intractable epileptic seizures are presented: (1) chronic electrical stimulation of the centromedian–thalamic nucleus (ESCM) for control of generalized tonic–clonic seizures and atypical absences, and (2) subacute hippocampal stimulation (SAHCS) and chronic hippocampal stimulation for control of nonlesional temporal lobe seizures. The ESCM antiepileptic effect seems to be the result of activation of a nonspecific reticulothalamocortical system responsible for generalized electrocortical responses (recruiting, desynchronization, negative direct current shifts, and three spike–wave complexes per second). The success of the ESCM procedure depends on the following predictor factors: case selection (primary and secondary tonic–clonic seizures and atypical absences of the Lennox Gastaut syndrome), ventriculographic and electrophysiologic definition of the optimal stereotactic targets (based on the anterior commissure, posterior commissure, and the vertical line perpendicular to the posterior commissure and electrocortical recruiting responses), periodic electrophysiologic monitoring of the reliability of ESCM in the absence of the patient’s subjective sensations and with totally internalized subcutaneous stimulation systems (by recording scalp electrocortical recruiting, desynchronizing, and direct current responses), quantitative evaluation of clinical and EEG improvement, and analysis of the ON and OFF effects, taking into account a long-lasting (possibly plastic) effect of ESCM. SAHCS blocks clinical and EEG signs of temporal lobe epileptogenesis with no additional damage of the stimulated hippocampal tissue. Preliminary results suggest that this antiepileptic effect is, at least in part, the result of a physiologic inhibition of the stimulated hippocampal tissue, because after SAHCS the authors found the following: (1) increased threshold and decreased duration, propagation, and blockage of the clinical signs accompanied with the hippocampal afterdischarge; (2) flattening of the hippocampal-evoked response recovery cycles; (3) single photon emission computed tomographic hypoperfusion; and (4) increased concentration of benzodiazepine receptor binding at the stimulated hippocampal region. Chronic hippocampal stimulation persistently blocked temporal lobe epileptogenesis in one patient under open protocols during 24 months with no apparent additional alterations in recent memory.

Electrical Stimulation for Epilepsy: Stimulation of Hippocampal Foci

Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21– 1.0 ms, 2.5–3.5 V (about 200–300 µA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

Acute and Chronic Electrical Stimulation of the Centromedian Thalamic Nucleus: Modulation of Reticulo-Cortical Systems and Predictor Factors for Generalized Seizure Control

The present report recapitulates the clinical and electrophysiologic studies we have performed on patients with certain forms of medically intractable epilepsy to investigate the basic mechanisms and predictor factors for seizure control of the electrical stimulation of the thalamic centromedian nucleus (CM) procedure. Acute electrical stimulation of CM reveals that in humans, as in other animals, CM represents a thalamic relay of a reticulo-cortical system that participates crucially in wakefulness and attentive processes and in regulation of cortical excitability, as well as in the physiopathology of genuine generalized epileptic seizures. For example, unilateral, threshold, low-frequency (6/sec) stimulation of CM produced electrocortical incremental responses, while high-frequency (60/sec) stimulation of CM produced electroencephalogram (EEG) desynchronization and electronegative DC shifts with no behavioral counterparts. In contrast, combined suprathreshold low-frequency (3/sec) stimulation of CM on one side and of mesencephalic reticular stimulation on the other produced generalized spike-wave complex discharges accompanied by the symptoms of a typical absence attack, including motionless stare, eye blinking, and unresponsiveness of patients to a series of flashes under a simple response task. Chronic bilateral, threshold, high-frequency (60/sec) stimulation of CM significantly decreased the number of primary and secondary generalized tonic-clonic seizures and atypical absence attacks and the amount of interictal generalized EEG discharges in both. In addition, it improved the psychological performance of patients and normalized the EEG by increasing the frequency of background EEG activity. In contrast, chronic stimulation of CM reduced neither the number of complex partial seizures nor the epileptic EEG activities localized in the temporal region. Good outcomes of the chronic CM stimulation procedure were achieved depending on correct selection of patients and accuracy of ventriculographic stereotactic targets, as well as on periodic clinical and EEG evaluation and electrophysiologic monitoring of CM electrical stimulation reliability. However, the presence of 3- to 6-month long-lasting effects of CM stimulation made statistical evaluation of ON-OFF effects of CM stimulation under placebo, double-masked randomized experiments difficult.

Effect of Chronic Electrical Stimulation of the Centromedian Thalamic Nuclei on Various Intractable Seizure Patterns: I. Clinical Seizures and Paroxysmal EEG Activity

Twenty‐three patients with various intractable seizure patterns were divided into four groups based on their most frequent seizure type and their clinical and EEG response to chronic electrical stimulation of the centromedian thalamic nuclei (ESCM): group A, generalized tonic‐clonic (GTC, n = 9); group B, partial motor (Rasmussen type) (n = 3); group C, complex partial seizures (CPS, n = 5); and group D, generalized tonic seizures (Lennox‐Gastaut type) (n = 6). CM were radiologically and electrophysiologically localized by means of stereotaxic landmarks and by thalamically induced scalp recruitinglike responses and desynchronization. ESCM consisted of daily 2‐h stimulation sessions for 3 months. Each stimulus consisted of a 1‐min train of square pulses with a 4‐min interstimulus interval, alternating right and left CM. Each pulse was 1.0 ms in duration at 60/s frequency and 8–15 V (400–1,250 μ‐A) amplitude. Voltage (V), current flow (μA) and impedance (kΩ) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10‐s epochs occurred in group A patients between the baseline period (BL) and the ESCM period. These changes persisted for >3 months after discontinuation of ESCM (poststimulation period, Post). Post was accompanied by a significant decrease in the number of paroxysmal EEG discharges. A substantial decrease in seizures and paroxysmal discharges was also observed in patients of group B. In contrast, patients of groups C and D showed no significant changes from BL to ESCM and Post periods, except for a significant decrease in the number of seizures in group D patients from BL to Post periods.

Electrical stimulation of the prelemniscal radiation in the treatment of Parkinson's disease: an old target revised with new techniques.

OBJECTIVEIn the treatment of tremor and rigidity in patients with Parkinson’s disease (PD), the prelemniscal radiation (RAPRL), a subthalamic bundle of fibers, is an exquisite target that can be visualized easily on ventriculograms. We sought to evaluate the effect of electrical stimulation of the RAPRL on symptoms and signs of PD in a long-term trial and to determine the localization of the stimulated area by means of stereotactic magnetic resonance imaging studies. METHODSTen patients with PD predominantly on one side had tetrapolar electrodes stereotactically oriented through a frontal parasagittal approach to the RAPRL contralateral to the most prominent symptoms. Preoperative and postoperative evaluations at 3, 6, 9, and 12 months after surgery were performed using conventional PD scales and quantitative evaluations of tremor amplitude and reaction time. Stereotactic high-resolution magnetic resonance imaging studies with the electrodes in place were used for anatomic localization. RESULTSIn all patients, temporary suppression of tremor occurred when the electrodes reached the target. The most effective stimulation was obtained when the pair of contacts was placed in the RAPRL. Long-term stimulation at 130 Hz, 0.09 to 0.450 milliseconds, and 1.5 to 3.0 V produced significant improvement in tremor and rigidity and mild improvement in bradykinesia. CONCLUSIONThe RAPRL is an effective target for the alleviation of tremor and rigidity in patients with PD by either lesioning or neuromodulation; however, neuromodulation has the advantage of not inducing an increase in bradykinesia. The stimulated area seems to be independent of the subthalamic nucleus.