Summary:Purpose: Our aim was to evaluate the efficacy of ESCM (electrical stimulation of the centromedian thalamic nucleus) in treatment of generalized seizures of the LennoxGastaut syndrome (LGS) and improvement of patient disability.Methods: Thirteen patients with LGS were studied. They had severe generalized tonic-clonic seizures (GTC) and atypical absences (AA). All patients had at least a 6-month baseline before bilateral electrode implantation to the centromedian (CM) nuclei of the thalamus to undergo therapeutic ESCM. Once implanted, electrodes were temporally externalized through a retromastoid point for electrophysiologic confirmation of their placement. After target confirmation, stimulation parameters were set. Patients came for follow-up assessment of seizures and neurophysiologic tests every 3 months during an 18-month period of time; AED therapy was not modified.Results: The surgical procedure as well as electrical stimulation was well tolerated by all patients. No side effects occurred with the therapeutic stimulation parameters used, and patients were not aware of device activation. Two patients were explanted because of repeated and multiple skin erosions that could not be controlled by plastic surgery procedures. Overall seizure reduction was 80%. The three patients with poorest outcomes for seizure control did not improve their ability scale score. In contrast, the two patients rendered seizure free are living a normal life at present. The remaining eight patients experienced progressive improvement, from being totally disabled to becoming independent in five cases and partially dependent in two. Patients with adequate electrode placement had a seizure reduction >87%. To consider that an electrode is correctly placed, both stereotactic placement and neurophysiologic responses are taken into account.Conclusions: ESCM provides a nonlesional, neuromodulatory method with improvement in seizure outcome and in the abilities of patients with severe LGS.

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. Methods: Nine patients were included. All had refractory partial complex seizures, some with secondary generalizations. All patients had a 3‐month‐baseline‐seizure count, after which they underwent bilateral hippocampal diagnostic electrode implantation to establish focus laterality and location. Three patients had bilateral, and six, unilateral foci. Diagnostic electrodes were explanted and definitive Medtronic electrodes were implanted directed into the hippocampal foci. Position was confirmed with MRI and afterwards, the deep brain stimulation system internalized. Patients signed the informed consent approved by the Hospital's Ethics Committee and began a double‐blind stimulation protocol. Patients attended a medical appointment every 3 months for seizure diary collection, deep brain stimulation system checkup, and neuropsychological testing. Results: Follow‐up ranged from 18 months to 7 years. Patients were divided in two groups: five had normal MRIs and seizure reduction of >95%, while four had hippocampal sclerosis and seizure reduction of 50–70%. No patient had neuropsychological deterioration, nor did any patient show side effects. Three patients were explanted after 2 years due to skin erosion in the trajectory of the system. Conclusions: Electrical stimulation of the hippocampus provides a nonlesional method that improves seizure outcome without memory deterioration in patients with hippocampal epileptic foci.

Summary:Purpose: To investigate the clinical, electroencephalographic (EEG), and histopathologic effects of subacute electrical stimulation of the hippocampal formation or gyrus (SAHCS) on 10 patients with intractable temporal lobe seizures.Methods: Bilateral, depth, hippocampal or unilateral, subdural, basotemporal electrodes were implanted in all 10 patients for a topographic diagnosis of the site and extent of the epileptic focus before a temporal lobectomy. In all patients, antiepileptic drugs (AEDs) were discontinued from 48 to 72 h before a program of continuous SAHCS, which was performed for 2-3 weeks. Stimulation parameters were biphasic Lilly wave pulses, 1301s in frequency, 450 p. s in duration, and 200-400 p,A in amplitude. The stimuli were delivered 23 of every 24 h for the 2-3-week SAHCS period. The effects of SAHCS on the number of clinical seizures per day and the percentage of interictal EEG spikes per 10-second samples of maximal paroxysmal activity at the epileptic focus were determined daily during the 16 days of SAHCS. At the completion of this program, patients underwent an en bloc temporal lobectomy, and the histopathologic effects of SAHCS on the stimulated tissue were analyzed by means of light-microscopy studies.Results: In seven patients whose stimulation electrode contacts were placed within the hippocampal formation or gyrus and who experienced no interruption in the stimulation pro- creased the number of interictal EEG spikes at the focus after 5-6 days. The most evident and fast responses were found by stimulating either the anterior pes hippocampus close to the amygdala or the anterior parahippocampal gyrus close to the entorhinal cortex. Other surface, hippocampal, and basotemporal EEG signs predicted and accompanied this antiepileptic response. These included an electropositive DC shift and monomorphic delta activity at the medial hippocampal and parahippocampal regions, and a normalization of the background EEG activity and signs of slow-wave sleep in surface, depth, and subdural regions. In contrast, no evident antiepileptic responses or no responses at all were found in three patients when stimulation was either interrupted or when it was adniinistered outside the hippocampus.Light microscopy analysis of the stimulated hippocampal tissue showed histopathological abnormalities attributable to the depth-electrode penetration damage or to the pial surface reaction to the subdural, Silastic electrode plate. However, no evident histopathological differences were found between the stimulated and nonstimulated hippocampal tissue.Conclusions: SAHCS appears to be a safe procedure that can suppress temporal lobe epileptogenesis with no additional damage to the stimulated tissue.

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 Zung's rated depression scale. Tests were evaluated for significant changes by the parametric student's t 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 afterdischarge (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 hyperexcitability of stimulated tissue, similar to "kindling," was created by chronic ES.

Summary: Purpose:The efficacy and safety of cerebellar stimulation (CS) was reevaluated in a double-blind, randomized controlled pilot study on five patients with medically refractory motor seizures, and especially generalized tonic-clonic seizures.Methods: Bilateral modified four-contact plate electrodes were placed on the cerebellar superomedial surface through two suboccipital burr holes. The implanted programmable, batteryoperated stimulator was adjusted to 2.0 µC/cm 2 /phase with the stimulator case as the anode; at this level, no patient experienced the stimulation. Patients served as their own controls, comparing their seizure frequency in preimplant basal phase (BL) of 3 months with the postimplant phases from 10 months to 4 years (average, eight epochs of 3 months each). During the month after implantation, the stimulators were not activated. The patient and the evaluator were blinded as to the next 3-month epoch, as to whether stimulation was used. The patients were randomized into two groups: three with the stimulator ON and two with the stimulator OFF. After a 4-month postimplantation period, all patients had their stimulator ON until the end of the study and beyond. Medication was maintained unchanged throughout the study. EEG paroxysmal discharges also were measured.Results: Generalized tonic-clonic seizures: in the initial 3-month double-blind phase, two patients were monitored with the stimulation OFF; no change was found in the mean seizure rate (patient 1, 100%, and patient 5, 85%; mean, 93%), whereas the three patients with the stimulation initially ON had a reduction of seizures to 33% (patient 2, 21%; patient 3, 46%; patient 4, 32%) with a statistically significant difference between OFF and ON phase of p = 0.023. All five patients then were stimulated and monitored. At the end of the next 6 months of stimulation, the five patients had a mean seizure rate of 41% (14-75%) of the BL. The second patient developed an infection in the implanted system, which had to be removed after 11 months of stimulation; the seizures were being reduced with stimulation to a mean of one per month from a mean of 4.7 per month (BL level) before stimulation. At the end of 24 months, three patients were monitored with stimulation, resulting in a further reduction of seizures to 24% (11-38%). Tonic seizures: four patients had these seizures, which at 24 months were reduced to 43% (10-76%). Follow-up surgery was necessary in four patients because of infection in one patient and lead/electrode displacement needing repositioning in three patients. The statistical analysis showed a significant reduction in tonic-clonic seizures (p < 0.001) and tonic seizures (p < 0.05).Conclusions: The superomedial cerebellar cortex appears to be a significantly effective and safe target for electrical stimulation for decreasing motor seizures over the long term. The effect shows generalized tonic-clonic seizure reduction after 1-2 months and continues to decrease over the first 6 months and then maintains this effectiveness over the st...

ESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

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.

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