[Central nervous system neuromodulation for the treatment of epilepsy]. / Neuromodulation du système nerveux central dans le traitement des épilepsies I-Efficacité 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.

Neuromodulation of prelemniscal radiations in the treatment of Parkinson's disease.

In patients with Parkinson's disease (PD), tetrapolar electrodes were implanted in the prelemniscal radiations (RAPRL) to treat tremor, rigidity and bradykinesia. Fifteen patients were implanted unilaterally and five patients bilaterally and followed-up for one year. The selection criteria included the presence of unilateral pronounced tremor and rigidity in patients implanted unilaterally or bilateral symptoms including severe bradykinesia in patients implanted bilaterally. In the operating room, the tremor decreased significantly or was abolished following the insertion of the electrode in the RAPRL. This effect was temporary and subsided when the stimulation was off. However, when the stimulator was turned on, the severity of the symptoms and signs decreased significantly. The post-implantation MRI confirmed that the electrode contacts used for stimulation were inserted in RAPRL, a group of fibers located between the red nucleus and subthalamic nucleus, above the substantia nigra, medially to the zona incerta and below the thalamus. The patients were evaluated using the UPDRS part III, before implantation and every 3 months during the first year. Global scores decreased significantly. The pre- and postoperative median values (range in round brackets) were as follows: tremor improved from 3 (2-16) to 1 (2-3) (p<0.001); rigidity was either abolished or decreased markedly from 2 (1-16) to 0 (0-4) (p< 0.001); bradykinesia improved from 2 (0-4) to 1 (0-2) (p<0.001). We conclude that RAPRL, an area anatomically different from STN, is a good target for electrical stimulation in order to treat effectively all the main symptoms of PD.

Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder.

Neuromodulation of the inferior thalamic peduncle is a new surgical treatment for major depression and obsessive-compulsive disorder. The inferior thalamic peduncle is a bundle of fibers connecting the orbito-frontal cortex with the non-specific thalamic system in a small area behind the fornix and anterior to the polar reticular thalamic nucleus. Electrical stimulation elicits characteristic frontal cortical responses (recruiting responses and direct current (DC)-shift) that confirm correct localization of this anatomical structure. A female with depression for 23 years and a male with obsessive-compulsive disorder for 9 years had stereotactic implantation of electrodes in the inferior thalamic peduncle and were evaluated over a long-term period. Initial OFF stimulation period (1 month) showed no consistent changes in the Hamilton Depression Scale (HAM-D), Yale Brown Obsessive Compulsive Scale (YBOCS), or Global Assessment of Functioning scale (GAF). The ON stimulation period (3-5 V, 130-Hz frequency, 450-msec pulse width in a continuous program) showed significant decrease in depression, obsession, and compulsion symptoms. GAF improved significantly in both cases. The neuropsychological tests battery showed no significant changes except from a reduction in the perseverative response of the obsessive-compulsive patient and better performance in manual praxias of the female depressive patient. Moderate increase in weight (5 kg on average) was observed in both cases.

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

OBJECTIVE: In 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. METHODS: Ten 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. RESULTS: In 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. CONCLUSION: The 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.

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 microA) 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.

Stimulation of the central median thalamic nucleus for epilepsy.

Electrical stimulation of the centromedian thalamic nucleus (ESCM) has been used in cases of difficult to control seizures with multifocal onset in frontal and temporal lobes, as well as in cases of seizures with no evidence of focal onset, such as Lennox-Gastaut syndrome. The stimulation program consists of 1 min stimulation on one side, 4 min interval OFF stimulation and 1 min stimulation on the other side, alternating from one side to the other for 24 h, at 60-130 Hz, 2.5-5.0 V, 0.21-0.45 ms. 49 cases have been treated and followed for periods of 6 months to 15 years. Results indicate that ESCM is highly efficient to control generalized tonic clonic seizures (GTC), atypical absences (AA) and tonic seizures (TS) and less efficient to control complex partial seizures (CxP).

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

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.

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.

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.

Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus.

OBJECTIVE: To evaluate the efficacy of chronic electrical stimulation of centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control seizures. METHODS: Thirteen patients underwent ESCM for periods ranging from 12 to 94 months (mean, 41.2 mo) with electrodes stereotactically placed in both centromedian nuclei and connected to internalized stimulation systems. Electrode placement was guided by ventriculography and confirmed with magnetic resonance imaging before stimulation systems were internalized. Anatomic and electrophysiological confirmation of the electrodes' position was accomplished by plotting electrode position on anatomic sections of Schaltenbrand and Bailey's atlas, and testing cortical recruiting responses and electroencephalogram desynchronization elicited by acute low- or high-frequency stimulation, respectively. RESULTS: Improvement was highly significant for generalized tonicoclonic seizures and atypical absences. Better results were obtained for Lennox-Gastaut syndrome. These results were accompanied by a significant decrease in generalized spike-wave and secondary synchronous discharges, as well as focal spikes in the frontal regions. In contrast, ESCM reduced neither complex partial seizures nor focal spikes in temporal regions. Outcomes using ESCM for generalized epilepsy were better in patients in whom anatomic and electrophysiological confirmation of electrode placement was correct than in those in whom the target was missed bilaterally (P < 0.001). The effect was sustained during the observation period and was better for longer-term than for shorter-term stimulation periods. CONCLUSION: ESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

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

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, 130/s in frequency, 450 micros in duration, and 200-400 microA 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 program, SAHCS abolished clinical seizures and significantly decreased 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 administered 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.

Effect of fentanyl and naloxone on a thalamic induced painful response in intractable epileptic patients.

Acute high-frequency (60/s) high-intensity (2,100-2,300 microA) stimulation of the mesial, caudal and inferior portion of the centromedian thalamic region within or close to the parafascicular nucleus produced a sharp, intense, cramp-like painful response localized to the face and shoulder (medial stimulation) or arm and hand (lateral stimulation) contralateral to the stimulation site in 4 intractable epileptic patients in whom depth electrodes had been implanted as a part of a neuroaugmentive procedure for seizure control. This thalamic induced painful response was always accompanied by objective clinical signs (facial gesticulation and contraction of the corresponding muscles) during thalamic stimulation and significant increments in EEG, EKG and respiratory frequencies and EMG muscular tonus from 10 s before to 10 s after thalamic stimulation. Opioid agonists (fentanyl 5.0 microg/kg) and antagonists (naloxone 3.5 microg/kg) were administered to induce and regulate a state of neuroleptanalgesia used for the subcutaneous internalization of the chronic stimulation systems. Under these conditions, we observed that fentanyl greatly attenuated and naloxone increased the intensity of the painful response, as well as the EEG, somatic and vegetative parameters evaluating such a painful response. Differences were significant when one compares the changes in response to electrical stimulation in EEG, EKG, respiration and EMG after the administration of fentanyl (decrease p = 0.001) and naloxone (increase p = 0.01) compared to those obtained after the administration of saline or no drugs during baseline recordings. These data suggest that this thalamic induced painful response is mediated by inhibition or activation of the morphine receptors of the thalamic cells primarily related to the pain process.

Temporo-spacial correlations between cortical and subcortical EEG spike-wave complexes of the Idiopathic Lennox-Gastaut syndrome.

All-night EEG recordings of the interictal 2/s spike-wave complexes (SKW) from different cortical and subcortical regions were performed in 5 patients with atypical absences of the Idiopathic Lennox-Gastaut syndrome (ILGS), in whom multicontact depth electrodes were implanted in the centromedian thalamic region as a part of a neuroaugmentive procedure for seizure control. Since during slow wave sleep III cortical spike (S2) and subcortical negative spike (NSK) consisting of simple monophasic negative potentials appeared together with a ratio of almost 1:1 and with fixed temporal relations, it was possible to determine visually the differences in peak-to-peak intervals of S2 and NSK, as well as their amplitude distribution in different cortical and subcortical structures. It was found that the peak of subcortical NSK preceded by 35 ms that of cortical S2. In addition, subcortical NSK and cortical S2 potentials attained maximal amplitude at the mesencephalic-thalamic reticular and frontal cortical regions, respectively, from which amplitude of NSK and S2 decreased with distance to other subcortical and cortical regions. These data suggest that interictal 2/s SKW of the ILGS result from ascending reticular impulses impinging upon the frontal cortical neurons.

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

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-microA 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 Student's 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 background 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.

Long-term effects of medical and surgical treatments on Parkinson's disease.

Three groups of patients with Parkinson's disease (PD) were studied: (1) PD patients treated medically with L-Dopa and anticholinergics, (2) PD patients treated with thalamo-subthalamotomies plus medical treatment, and (3) PD patients treated with autologous adrenal medullary transplantation to right caudate nucleus plus medical treatment. Evaluations prior and 1, 6 and 12 months after treatment were accomplished with PD scales (NYPDS, UPDS, Schwab and England and Hoehn and Yahr scales). No attempt was made to compare one PD after treatment in each group. Statistical analysis was performed with the Friedman-Anova test. Group 1 did not show significant improvement at any time but deterioration at 12 months. Group 2 showed significant improvement at 1 month but at 12 months deterioration occurred mainly in the mental condition and akinesia. Group 3 did not show significant improvement at any time but at 12 months there was a tendency of improvement in self-sufficiency.

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 recruiting-like 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 microA) amplitude. Voltage (V), current flow (microA) and impedance (k omega) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10-s spochs 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.

Effect of chronic electrical stimulation of the centromedian thalamic nuclei on various intractable seizure patterns: II. Psychological performance and background EEG activity.

We studied the effect of electrical stimulation of centromedian thalamic nuclei (ESCM) on seizure control and paroxysmal EEG activity in 23 patients. We report the effect of chronic ESCM on psychological performance and background EEG activity of patients with various intractable seizure patterns. In each patient, a simple specifically designed neuropsychological scales (one for adults and one for children) was administered at the end of the baseline (BL), ESCM, and poststimulation (Post) periods; and 14 consecutive EEG recordings during these periods were performed to determine the degree of neuropsychological improvement and the temporal course of EEG changes. A significant increase in psychological scores and the number of background EEG waves per 10 s was noted in groups A (generalized tonic-clonic seizures, GTC), C (complex partial seizures, CPS), and D (generalized tonic seizures) and the total group of patients from BL to ESCM and from BL to Post periods. Group B patients showed a substantial increase (partial motor seizures) during the same periods. Improvement on psychological performance correlated better with age and baseline degree of deterioration than with the nature of the particular psychological improvement in any given subtest. The improvement in EEG background rhythm was most noticeable at the end of ESCM and at the beginning of the Post periods. Complete normalization of neuropsychologic scores and EEG rhythms was rare, but improvement was significant for both. Psychological scores increased from BL 14 +/- 2 to ESCM 21 +/- 2 and Post 23 +/- 2 (normal expected 26), and EEG background rhythm increased from BL 42 +/- 2 to ESCM 62 +/- 2 and Post 54 +/- 2 EEG waves/10 s. (normal expected > 80).

Subcortical correlates of the P300 potential complex in man to auditory stimuli.

Bipolar and referential responses correlated to the surface P300 auditory potential complex (components N2, P3 and N4) were studied in different subcortical structures of parkinsonian and epileptic patients with implanted electrodes used as an electrophysiological procedure for surgical treatment. Bipolar and referential subcortical responses were recorded from a wide subcortical region which included subthalamo-thalamic (Sth-Th), dorsothalamic (DTh), orbitofronto-hippocampal (OFH) and striatal (STR) structures. They were formed by 3 consecutive components C, D and E correlated to components N2, P3 and N4 of the surface responses. Component D correlated to surface P3 was either absent or very small in all subcortical bipolar responses and in referential responses recorded from OFH structures. Polarity of bipolar component C was inverted between DTh and OFH while that of bipolar component E was inverted between Sth-Th and DTh, between OFH and STR and between Sth-Th and STR. Polarity of the referential component C was inverted between STh-Th and DTh and between OFH and STR while that of referential components D and E remained unchanged along all subcortical structures. Referential components C-E and D attained maximal amplitudes and minimal latencies at the subthalamic and at the medial geniculate thalamic nucleus regions respectively. From here, their amplitudes decreased and latencies increased with distance in other structures rostrally and caudally located, with the exception of those at the orbitofrontal (components C-E) and dorsal thalamic and striatal regions (component D) where no amplitude-latency gradients were observed.