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.

Efficacy of motor cortex stimulation in the treatment of neuropathic pain: a randomized double-blind trial.

OBJECT: In this study the authors used a double-blind protocol to assess the efficacy of motor cortex stimulation (MCS) for treating neuropathic pain. METHODS: Eleven patients with unilateral neuropathic pain (visual analog scale [VAS] score 8-10) of different origins and topography were selected for MCS. A 20-contact grid was implanted through a craniotomy centered over the motor cortex contralateral to the painful area. The motor cortex strip was identified using neuroimages, somatosensory evoked potentials, acute electrical stimulation, and corticocortical evoked potentials. Subacute therapeutic stimulation trials allowed the authors to determine the most efficient pair of contacts to use for long-term MCS. The grid was replaced with a 4-contact electrode connected to an internalized stimulator. Bipolar stimulation at a 40-Hz frequency, 90-micro sec pulse width, amplitude 2-7 V, and 1 hour in "ON" and 4 hours in "OFF" mode was used. Pain was evaluated using the VAS, Bourhis, and McGill pain scales applied each month for 1 year. At Day 60 or 90, the stimulators were turned to OFF mode for 30 days in a randomized, double-blind fashion. The statistical tool used was the Wilcoxon test. RESULTS: Three patients did not report improvement in the subacute trial and were excluded from long-term MCS; the remaining patients underwent long-term stimulation. Significant improvement of pain was induced by MCS (p < 0.01); this persisted during the follow-up period. Turning stimulation to OFF mode increased pain significantly (p < 0.05). Improvement at 1 year was >or= 40% (40-86%) in all cases. CONCLUSIONS: Motor cortex stimulation is an efficient treatment for neuropathic pain, according to an evaluation facilitated by a double-blind maneuver. Subacute stimulation trials are recommended to determine the optimum motor cortex area to be stimulated and to identify nonresponders.

Opioid receptor binding in parahippocampus of patients with temporal lobe epilepsy: its association with the antiepileptic effects of subacute electrical stimulation.

Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained from patients with intractable mesial temporal lobe epilepsy (MTLE) with and without subacute high frequency electrical stimulation (HFS) in this brain area. Mu, delta and nociceptin receptor binding was determined by autoradiography in PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial sclerosis. This group demonstrated antiepileptic effects following subacute HFS (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE, 693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE, 424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic groups. However, tissue obtained from ESAE group demonstrated lower opioid receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H-nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results indicate that a high effectiveness to the antiepileptic effects induced by HFS is associated with reduced opioid peptide binding.

Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with Lennox-Gastaut syndrome.

PURPOSE: Our aim was to evaluate the efficacy of ESCM (electrical stimulation of the centromedian thalamic nucleus) in treatment of generalized seizures of the Lennox-Gastaut 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.

Electrocortical and behavioral responses elicited by acute electrical stimulation of inferior thalamic peduncle and nucleus reticularis thalami in a patient with major depression disorder.

OBJECTIVE: Our aim was to study electrocortical and behavioral responses elicited by 6, 60 and 3/s stimulation of the inferior thalamic peduncle (ITP) and nucleus reticularis thalami (Re) in a patient with of major depression disorder resistant to psychotherapy, pharmacotherapy and electroconvulsive therapy and candidate to be treated by electrical stimulation of the ITP. METHODS: In this patient, two multicontact electrodes were implanted bilaterally through frontal coronal parasagittal burr-holes with oblique trajectories aiming ITP and Re. Stimulation was performed through externalized systems. Referential scalp electroencephalographic (EEG) recordings were performed and subjective sensations and clinical symptoms reported by patient and changes in responsiveness in single response tasks during stimulation trials were systematically recorded. RESULTS: Unilateral, low (6/s) and high (60/s) frequency stimulation of either ITP or Re produced identical recruiting-like responses or desynchronization-DC shift changes predominant at frontopolar region, bilaterally. Billateral, high intensity 3/s stimulation or either ITP or Re produced electrocortical responses that consisted in generalized 3/s spike-wave complexes predominant at frontopolar, frontocentral and frontotemporal regions. However, while ITP responses were accompanied by all symptoms described for a spontaneous absence attack, Re responses were behaviorly accompanied only by delayed reaction time. CONCLUSION: These data suggests that in humans as in cats, ITP and Re are both part of a non-specific thalamo-orbitofrontal system normally engaged in cortical synchronization, selective attention and sleep. SIGNIFICANCE: Under abnormal conditions, ITP and RE may play a role in the physiopathology of typical absence attacks and depression disorders.

Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders.

OBJECTIVE: To present a review of evidence for an inhibitory thalamo-orbitofrontal system related to physiopathology of major depression disorders (MDDs) and to postulate that interfering with hyperactivity of the thalamo-orbitofrontal system by means of chronic high-frequency electrical stimulation of its main fiber connection, the inferior thalamic peduncle (ITP), may result in an improvement in patients with MDD. METHODS: Experimentally, the thalamo-orbitofrontal system has been proposed as part of the nonspecific thalamic system. Under normal conditions, the nonspecific thalamic system induces characteristic electrocortical synchronization in the form of recruiting responses that mimic some sleep stages. It also inhibits input of irrelevant sensory stimuli, thus facilitating the process of selective attention. Permanent disruption of the system, via lesioning or temporary inactivation through cooling of the ITP with cryoprobes, results in a state of hyperkinesia, increased attention, and cortical desynchronization. RESULTS: Surgical lesioning of the medial part of orbitofrontal cortex and white matter overlying area 13, which includes the ITP, may result in significant improvement in MDD. Imaging studies (functional magnetic resonance imaging and positron emission tomography) consistently demonstrate hyperactivity in the orbitofrontal cortex and midline thalamic regions during episodes of MDD. This hyperactivity decreases with efficient control of MDD by medical treatment, indicating that orbitofrontal cortex and midline thalamic overactivity are related to the depressive condition. Conversely, noradrenergic and serotoninergic systems in the frontal lobes have been implicated in the pathophysiology of MDD. Although noradrenergic receptor density in the frontal lobe is consistently increased in depressed patients who commit suicide, 5-hydroxytryptamine reuptake blockers, which are potent antidepressive drugs, decrease hypermetabolism in the orbital frontal cortex in MDD. Therefore, the serotonin hypothesis for depression postulates that norepinephrine and serotonin in the frontal lobes are required to maintain antidepressive responsiveness. Dysregulation of the secretion of both neurotransmitters initiates overactivity of orbitofrontal cortex, resulting in depression. It is possible that surgical interventions in this region, including electrical stimulation of ITP, disrupt adrenergic and serotoninergic dysregulation in patients with MDD. CONCLUSION: Circumscribed lesions or electrical stimulation of the ITP, a discrete target easily identified by electrophysiological studies, may improve MDD. Electrical stimulation may have the advantage of being less invasive and more adjustable to patient needs.

Evaluation of GABA system and cell damage in parahippocampus of patients with temporal lobe epilepsy showing antiepileptic effects after subacute electrical stimulation.

PURPOSE: The gamma-aminobutyric acid (GABA) system and neuronal loss were evaluated in the parahippocampal cortex (PHC) of patients with intractable mesial temporal lobe epilepsy (MTLE) who received subacute electrical stimulation and showed antiepileptic effects. METHODS: GABA tissue content, GABA(A) and benzodiazepine (BZD) receptor levels, as well as neuronal density were determined in PHC of five patients (ESAE group) with an MTLE history of 14.8 +/- 2.5 years and seizure frequency of 11 +/- 2.9 per month, two (40%) of them with mesial sclerosis. This group demonstrated antiepileptic effects after subacute electrical stimulation (130 Hz, 450 micros, 200-400 microA), applied continuously during 16 to 20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4), and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). RESULTS: The ESAE group demonstrated high GABA tissue levels (219%), as well as a significantly higher cell count (58.5%) when compared with the MTLE group. The ESWAE group showed enhanced BZD-receptor levels (38%), whereas their values for GABA tissue levels and GABA(A) receptor were similar to those obtained from the MTLE group. CONCLUSIONS: It is suggested that subacute electrical stimulation of PHC is more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss.

Temporo-spatial correlations between scalp and centromedian thalamic EEG activities of stage II slow wave sleep in patients with generalized seizures of the cryptogenic Lennox-Gastaut syndrome.

OBJECTIVES: Temporo-spatial correlations between scalp and centromedian thalamic (CM) normal and abnormal electroencephalographic (EEG) activities of stage II slow wave sleep (SWS II) were investigated in 5 patients with cryptogenic Lennox-Gastaut syndrome (CLGS). METHODS: In each patient, 8h/all-night sleep studies were performed with routine methods; and a total of 1233 normal and 206 abnormal individual activities, spontaneously occurring during 200 epochs of early and late SWS II, were analyzed. Normal activities included scalp-CM K-complexes (KC-CMKC), vertex waves (VW-CMVW), and sleep spindles (SS-CMSS). Abnormal activities included: thalamo-cortical spikes (TCS-CMTCS), and epileptic (EPKC-CMEPKC) and W K-complexes (WKC-CMWKC). RESULTS: (1) All abnormal and normal spontaneous SWS II activities occurred associated in scalp and CM regions except the SS. Associated spindles were significantly larger (P<0.01) than dissociated ones, this occurring during both early and late SWS II. (2) The peak of VW significantly anticipated (P<0.02) that of its CM counterpart (CM-VW), while the peak of CMTCS anticipated that of its scalp counterpart. The onset of CMSS significantly anticipated (P=0.02) that of its scalp counterpart (SS). The behavior of VW-CMVW and TCS-CMTCS of the abnormal KC was similar to those of the normal complexes, while the onset of abnormal spindles was simultaneous in scalp and CM regions. Scalp VW, CTS, and SS attained maximal amplitude at the parietal region bilaterally with decreasing amplitude gradients to other scalp regions, while CMVW, CMTCS, and CMSS attained maximal amplitude in all thalamo-mesencephalic regions of CM. (3) Normal spindles significantly reduced (P<0.02) the amplitude of the positive CM, CMVW, and scalp TCS counterparts of the negative scalp VW and CM (CMTCS), respectively, while abnormal spindles reduced the amplitudes (P<0.01) of both negative VW and CMTCS and positive counterparts. CONCLUSION: These data suggest the following: (1) that all SWS II activities, including SS, are mediated by common thalamo-cortical systems; (2) that VW originate from the parietal scalp and normal spindles and TCS from the CM regions bilaterally while abnormal spindles originate either from widespread cortical and CM regions or from a site outside the thalamo-cortical systems, and (3) that the functional role of SS is to inhibit non-specific thalamo-cortical systems for sleep preservation.

Motor cortex stimulation in the treatment of deafferentation pain. I. Localization of the motor cortex.

MRI and electrophysiological techniques to localize the primary motor cortex (MC) were performed on patients considered for MC stimulation for the treatment of deafferentation pain. The representation and trajectory of the rolandic fissure (RF) were accurately localized by external cranial landmarks and radiopaque fiducials superimposed on oblique MRI sections. In addition, the scalp distribution of the corticocortical responses elicited by acute epidural stimulation [motor cortex (MC) in frontal and sensory cortex (SC) in parietal scalp regions], and analgesic responses at the topographical representation of the painful periphery elicited by subacute epidural stimulation were found to be simple and reliable procedures to localize MC, SC and RF.

Valor semiológico de los signos clínicos en el diagnóstico topográfico de las epilepsias refractarias: Epilepsias parciales / Semiologic value of the clinical signs in topographic diagnosis of the refractory epilepsies: Partial epipsies

El análisis de los síntomas y signos clínicos obtenidos por medio de un interrogatorio detallado y por la observación secuencial de los fenómenos motores a través de técnicas de monitoreo continua TV-EEG constituye una herramienta poderosa para establecer el diagnóstico topográfico de los pacientes con crisis parciales de difícil control en los cuales se complementa un tratamiento quirúrgico ablativo. Las alteraciones de la conciencia. Las auras y síntomas somatosensoriales, visuales y auditivos localizan el origen y la propagación de las crisis dentro de las cortezas primarias SI, VI y AI en el hemisferio. Los fenómenos motores representan la expresión sintomática de las crisis que se originan en, o se propagan a distinto territorios corticales: Las contracciones musculares focales con marcha Kachsoniana y parálisis de Tood apuntan al área Rolándica. El arreste conductual y los automatismos oroalimentarios y exploratorios al área temporal mesial. Los movimientos tónicos posicionales abruptos al área motora suplementaria; los movimiento versivos a las áreas frontopolar y dorsolateral; y la supresión del habla al opercular y al área temporal lateral. La progresión y secuencia de los síntomas y fenómenos motores durante las crisis permite diferenciar el origen (lesión, foco y área epileptógena) de la propagación (área sintomática) lo cual es factible en aquellas que se propagan lentamente a sitios distantes