Long-term directional deep brain stimulation: Monopolar review vs. local field potential guided programming.

BACKGROUND: Directional subthalamic stimulation in Parkinson's disease can increase stimulation threshold for adverse effects and widen the therapeutic window. However, selection of programming settings is time consuming, requiring a thorough monopolar clinical review. To overcome this, programming may be guided by intraoperatively recording local field potential beta oscillations (13-35 Hz). OBJECTIVES: 1) Evaluate whether the power of beta oscillations recorded intraoperatively can predict the clinically most effective directional contacts; and 2) assess long-term directional stimulation outcomes between patients programmed based on clinical monopolar review and patients programmed based on beta activity. METHODS: We conducted a non-randomized, prospective study with 24 Parkinson's disease patients divided into two groups. In group A (14 patients, 2016-2018), we investigated whether beta activity in the directional contacts correlated with clinical efficacy. Stimulating parameters were selected according to clinical monopolar review and mean follow-up was 27 months. In group B (10 patients, 2018-2019), stimulating parameters were selected according to beta activity and mean follow-up was 13 months. RESULTS: Neurophysiological results showed a strong correlation between clinical efficacy and the low-beta sub-band. Contacts with highest beta peaks increased the therapeutic window by 25%. Selecting the two contacts with highest beta peaks provided an 82% probability of selecting the best clinical contact. Clinical results showed similar improvements in group A (motor score, 72% reduction; levodopa-equivalent daily dose, 65% reduction) and B (72% and 63% reduction, respectively), maintained at long-term follow-up. CONCLUSIONS: Our results validate the long-term efficacy of directional stimulation guided by intraoperative local field potential beta oscillations.

Carisoprodol Single and Multiple Dose PK-PD. Part II: Pharmacodynamics Evaluation Method for Central Muscle Relaxants. Double-Blind Placebo-Controlled Clinical Trial in Healthy Volunteers.

Centrally acting skeletal muscle relaxants (CMR) such as carisoprodol are used to treat acute, painful musculoskeletal conditions, though its precise mode of action has not been characterized. A double-blinded, placebo-controlled, randomized clinical trial was designed to evaluate the pharmacokinetics-pharmacodynamics (PKPD) of CMR after single (350 mg), double (700 mg), and multiple doses (up to 350 mg/8 h, 14 days) of carisoprodol. Muscular (Electromyogram-EMG, muscular strength dynamometry), central (sedation), and tolerability (psychomotor activity test, adverse events) parameters, as well as withdrawal symptoms, were evaluated. Thirteen healthy volunteers were enrolled. No evidence of direct muscle relaxation was evidenced, but some differences on sedation were evidenced throughout the study, suggesting that CMRs act, at least partly, through sedation. Most significant differences were detected at 1.5 h after dosing. The effect on psychomotor impairment was variable, most prominently after 1.5 h, too, suggesting that it is produced by carisoprodol rather than by meprobamate. No withdrawal symptoms were detected, so the risk of dependence following maximum doses and duration of treatment recommended, and under medical supervision, should be low.

Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas.

OBJECTIVE The extent of resection is the most important prognostic factor following brain glioma surgery. However, eloquent areas within tumors limit the extent of resection and, thus, critically affect outcomes. The authors hypothesized that presurgical suppression of the eloquent areas within a tumor by continuous cortical electrical stimulation, coupled with appropriate behavioral training ("prehabilitation"), would induce plastic reorganization and enable a more extensive resection. METHODS The authors report on 5 patients harboring gliomas involving eloquent brain areas within tumors as identified on intraoperative stimulation mapping. A grid of electrodes was placed over the residual tumor, and continuous cortical electrical stimulation was targeted to the functional areas. The stimulation intensity was adjusted daily to provoke a mild functional impairment while the function was intensively trained. RESULTS The stimulation intensity required to impair function increased progressively in all patients, and all underwent another operation a mean of 33.6 days later (range 27-37 days), when the maximal stimulation voltage in all active contacts induced no functional deficit. In all cases, a substantially more extensive resection of the tumor was possible. Intraoperative mapping and functional MRI demonstrated a plastic reorganization, and most previously demonstrated eloquent areas within the tumor were silent, while there was new functional activation of brain areas in the same region or toward the contralateral hemisphere. CONCLUSIONS Prehabilitation with continuous cortical electrical stimulation and appropriate behavioral training prior to surgery in patients with WHO Grade II and III gliomas affecting eloquent areas accelerate plastic changes. This can help maximize tumor resection and, thus, improve survival while maintaining function.

High-frequency cortical subdural stimulation enhanced plasticity in surgery of a tumor in Broca's area.

Functional areas located near or within brain gliomas prevent the complete resection of these tumors. It has recently been described that slow tumor invasion promotes neural reorganization, and even topographic plasticity, allowing a staged resection of those tumors. Thus, our aim was to promote plasticity by mimicking the tumor's capability to displace brain function. This proceeded through the production of a 'virtual lesion' in eloquent areas within a tumor using continuous high-frequency cortical electrical stimulation (cHFCS). An anaplastic astrocytoma located in Broca's area progressed in a patient whose lateralization of language to the side of the lesion was demonstrated with functional MRI. After partial tumor resection using awake cortical monitoring, we implanted a subdural grid over the eloquent cortex located within residual tumor. We then applied cHFCS for 25 days, using a frequency of 130 Hz and a pulse width of 1 ms. Stimulus intensity was set to the threshold wherein mild speech disturbance was evident without any other neurological effects. This treatment successfully achieved the displacement of speech functions, and a more radical resection of the tumor was possible in a second surgery. Critically, a reorganization of motor language areas was demonstrated both with functional MRI and cortical stimulation. Furthermore, motor language areas were also identified in the right hemisphere, where previously they were absent. The patient's speech fluency improved both after stimulation and resection. We therefore demonstrate the first evidence of induced topographic plasticity using cHFCS in eloquent areas within a tumor, which allowed for increased tumor removal. Our results open the possibility to induce plasticity before the resection of brain tumors near eloquent areas, in order to increase the extent of resection.

rTMS stimulation to induce plastic changes at the language motor area in a patient with a left recidivant brain tumor affecting Broca's area.

INTRODUCTION: Extent of resection is one of the most powerful predictors of outcome in surgery of gliomas. Tumors located within areas governing eloquence may impede a total tumor resection. Functional plasticity may be induced by therapeutic means, such as cortical stimulation with repetitive transcranial magnetic stimulation (rTMS). Thus, rTMS is a potential tool to induce an improvement of functions of eloquence menaced by brain tumors. MATERIAL AND METHODS: We report a case of a 59-year-old woman operated for a left sided precentral oligodendroglioma with awake intraoperative stimulation, whose tumor could not be completely removed because it affected areas governing language. Nine months later the tumor progressed and the motor language functions worsened. We submitted the patient to rTMS directed to Broca's area, next to the anterior pole of the tumor, with the aim of improving motor language function before a new tumor resection attempt. We performed 12 daily sessions of theta-burst rTMS followed by intensive language rehabilitation for 10 minutes, and 5 different aspects of language were measured before, immediately after and 10 minutes after each session. RESULTS: Repetition and nomination worsened immediately after each rTMS session, and improved after 10 min of rehabilitation. However, basal values improved globally along the experiment. Also, the impact of rTMS on motor language was increasingly less along the procedure. CONCLUSIONS: rTMS induces changes in Broca's area and this effect can be potentially used to improve language function in tumors located at or close to eloquent cortical areas.

Electromyography evaluations of the masticator muscles during the maximum bite force

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Crisis del lóbulo temporal registrada mediante magnetoencefalografía: caso clínico / Temporal lobe seizure recorded by magnetoencephalography: case report

La localización del inicio de las crisis es un factor importante para la evaluación prequirúrgica de la epilepsia. En este trabajo se describe la localización del inicio de una crisis registrada mediante magnetoencefalografía (MEG) en un niño de 12 años que presenta crisis parciales complejas farmacorresistentes. La RM muestra una lesión de 20mm de diámetro en el hipocampo izquierdo. EEG de superficie con ondas theta temporales izquierdas. Registro MEG interictal con punta-onda aislada posterior e inferior a la lesión de la RM. Registro MEG ictal con punta-onda (2 Hz). La localización de los dipolos indica el inicio de la crisis en la circunvolución temporal inferior en la misma localización que la actividad interictal MEG. Esta actividad ictal se propaga bilateralmente a áreas frontales. El registro corticográfico intraquirúrgico confirma los resultados de la localización interictal mediante MEG.

[Temporal lobe seizure recorded by magnetoencephalography: case report]. / Crisis del lóbulo temporal registrada mediante magnetoencefalografía: caso clínico.

Ictal onset localization is a important factor in presurgical evaluation of epilepsy. This paper describes the localization of a seizure onset recorded by magnetoencephalography (MEG) from a 12-year-old male patient who suffered from complex partial drug-resistant seizures. MRI revealed a 20mm diameter lesion located in left hippocampus. Scalp EEG showed left temporal theta waves. Interictal MEG registrations detected isolated spike-wave activity posterior and inferior to the MRI lesion. Ictal MEG showed continuous spike-wave activity (2 Hz). Dipole localization sited seizure onset in the inferior left temporal gyrus, the same localization of the interictal MEG activity. This ictal activity spreads bilaterally to frontal areas. Intrasurgical electrocorticography recording confirmed interictal MEG results.

Can small lesions induce language reorganization as large lesions do?

Shift of the cortical mechanisms of language from the usually dominant left to the non-dominant right hemisphere has been demonstrated in the presence of large brain lesions. Here, we report a similar phenomenon in a patient with a cavernoma over the anterolateral superior temporal gyrus associated with epilepsy. Language mapping was performed by two complementary procedures, magnetoencephalography, and electrocorticography. The maps, indicated right temporal lobe dominance for receptive language and left frontal lobe dominance for expressive language. These results indicate that a small lesion, associated with epilepsy, may produce selective shifting of receptive language mechanisms as large lesions have been known to produce.