Gerson Ballester

Bilateral anterior thalamic nucleus lesions and high-frequency stimulation are protective against pilocarpine-induced seizures and status epilepticus.

OBJECTIVEThe thalamus is thought to play an important role in secondary generalization of seizures. The aim of the present study was to investigate the influence of anterior thalamic nucleus lesions and high-frequency stimulation in the pilocarpine model of secondarily generalized seizures in rats. METHODSAdult Wistar rats underwent unilateral (n = 7) or bilateral anterior nucleus thalamotomies (n = 10), or unilateral (n = 4) or bilateral (n = 9) anterior thalamic nucleus stimulation through implanted electrodes. Control animals (n = 9) received bilateral implants but no stimulation. Seven days after these procedures, animals were provided pilocarpine (320 mg/kg intraperitoneally) to induce seizures and status epilepticus (SE). Electrographic recordings from hippocampal and cortical electrodes were evaluated, and ictal behavior was assessed. RESULTSIn the control group, 67% of the animals developed SE 15.3 ± 8.8 minutes after pilocarpine administration. Neither unilateral anterior nucleus lesions nor stimulation significantly reduced the propensity or latency for developing seizures and SE. Bilateral thalamic stimulation did not prevent SE (observed in 56% of the animals), but it significantly prolonged the latency to its development (48.4 ± 17.7 min, P = 0.02). Strikingly, no animal with bilateral anterior nucleus thalamotomies developed seizures or SE with pilocarpine. CONCLUSIONBilateral anterior thalamic nuclear complex stimulation and thalamotomies were protective against SE induced by pilocarpine.

Motor cortex stimulation inhibits thalamic sensory neurons and enhances activity of PAG neurons: possible pathways for antinociception.

TOC summary Motor cortex stimulation‐induced analgesia occurs, at least in part, through the inhibition of the thalamic sensory neurons and the neuronal disinhibition in the periaqueductal gray. ABSTRACT Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian‐parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, δ‐aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation‐induced antinociception.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

Functional mapping of the motor cortex of the rat using transdural electrical stimulation

Motor cortex stimulation oriented by functional cortical mapping is used mainly for treating otherwise intractable neurological disorders, however, its mechanism of action remains elusive. Herein, we present a new method for functional mapping of the rat motor cortex using non-invasive transdural electrical stimulation. This method allows a non-invasive mapping of the surface of the neocortex providing a differentiation of representative motor areas. This study may facilitate further investigation about the mechanisms mediating the effects of electrical stimulation, possibly benefiting patients who do not respond to this neuromodulation therapy.

Stereotactic disconnection of hypothalamic hamartoma to control seizure and behavior disturbance: case report and literature review

An 18-year-old boy with refractory epilepsy and aggressiveness associated to a hypothalamic hamartoma was submitted to a stereotactically guided lesion by thermocoagulation. The target was based on magnetic resonance (MR) images merged with computed tomography scan images taken on the day of surgery while patient was on a stereotactic frame. In order to reveal structures not discernible in MR images, the Schaltenbrand digital brain atlas was merged onto the patient’s images. Target and trajectory of the depth electrode were chosen based on three-dimensional imaging reconstructions. A surgical plan was devised to disconnect the hypothalamic hamartoma from the hypothalamus, medial forebrain bundle, fasciculus princeps, and dorsal longitudinal fasciculus. Our target was placed at the inferior portion of the posterolateral component of the hamartoma, bordering the normal hypothalamus. The patient evolved with marked lessening of aggressiveness. Seizure frequency was reduced from several seizures per day to less than one tonic-clonic seizure during sleep per month and only two episodes suggestive of partial complex seizures during daytime. These results have remained consistent over a 24-month postoperative follow-up. Functional neuroanatomy of hypothalamic connections involved in seizure propagation and aggressive behavior was reviewed.

Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory

BackgroudIt has been shown that different symptoms or symptom combinations of neuropathic pain (NeP) may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI) is able to detect distinct clusters of symptoms (i.e. dimensions) with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV) of the NPSI.MethodsPatients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i) rate their mean pain intensity in the last 24 hours on an 11-point (0-10) numerical scale; (ii) complete the PV-NPSI; (iii) provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC) were filled out in the second visit.ResultsPV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms.ConclusionsThe psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.

Mapping of the Rat's Motor Area after Hemispherectomy: The Hemispheres as Potentially Independent Motor Brains

Summary:  Purpose: The remarkable motor recovery observed after hemispherectomy in patients and experimental animals has puzzled investigators, as it defies classic jacksonian neurology. Several mechanisms for this phenomenon have been considered, such as neuronal sprouting to subcortical structures, neurochemical changes, and cerebellar diaschisis. The spared hemisphere may, however, play a crucial part in this functional recovery.

Multifocal slow potential generation revealed by high-resolution EEG and current density reconstruction

In this work we used high-resolution EEG (123 channels) and current density reconstruction (CDR) to analyze the generators of slow potentials (SPs) in 31 healthy individuals. SPs were obtained during a task-performance feedback anticipation paradigm. The task consisted of a visual paired-associate memory test, with correct performance on single trials indicated by pleasant visual stimuli and incorrect performance by an unpleasant sound. We used realistic models of each subjects head based on their magnetic resonance images (MRIs) to estimate the potentials in the intracranial compartments and to define the source space using individual cortical geometry. Source reconstruction was performed by an Lp-norm minimization algorithm. Results showed a multifocal pattern of current density foci in various association cortices, including prefrontal areas 9 and 10 of Brodmann in all subjects. Posterior cortical areas also contributed importantly to the SP, for instance extrastriate area 19 and parietal area 7, in 90% of the subjects. According to our modeling, we conclude that even the pure stimulus-anticipation SP obtained here, as opposed to traditional motor-task contigent negative variation (CNVs), is not exclusively prefrontal in origin, being generated by multiple association areas. We discuss our results with respect to new possibilities in large-scale cortical physiology and with respect to their application in psychiatry.

Ischemic preconditioning and spinal cord function monitoring in the descending thoracic aorta approach

OBJECTIVES To evaluate the effectiveness of acute ischemic preconditioning (IP), based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal cord protection and to asses SSEP importance in spinal cord neuromonitoring. METHODS Twenty-eight dogs were submitted to spinal cord ischemic injury attained by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross-clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group that was previously submitted to IP. The IP cycles were determined based on SSEP changes. RESULTS Tarlov scores of the IP groups were significantly better than those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and in 6 from C60 group, although all dogs from IP45 group were neurologically normal, as 4 dogs from IP60. There was a significant correlation between SSEP recovery time until one hour of aortic reperfusion and the neurological status (p = 0.011), showing sensitivity of 75% and specificity of 83%. CONCLUSION Repetitive acute IP based on SSEP is a protection factor during spinal cord ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good neurological injury assessment method during surgical procedures that involve spinal cord ischemia.

Wavelet transform and cross-correlation as tools for seizure prediction

This paper describes the detection of preictal bursting using wavelet transform application and cross-correlation analysis. The wavelet transform is applied to data reduction and signal pre-processing. The extracted features provide simplified signals to process by means of the cross-correlation technique. The algorithm has been tested with a set of preictal data, interictal data and spontaneous crises, to determinate its sensitivity and its specificity (False Prediction Rate). The seizure occurrence period and the seizure prediction horizon are also calculated. The algorithms merits are: 1) high sensitivity and 2) easy implementation.