Joacir Graciolli Cordeiro

Seizure control resulting from intrahippocampal depth electrode insertion

Deep brain stimulation in the treatment of pharmacoresistant epilepsy has gained increasing interest in recent years. Different targets are being chosen to modulate epileptic activity, including areas modifying seizure spread (eg, thalamus and subthalamic nucleus) and the primary epileptogenic focus (neocortical and hippocampal stimulation1 2). In patients undergoing thalamic stimulation, permanent effects of the implantation of stimulation electrodes have been reported in the treatment of Parkinsons disease, pain and epilepsy.3 We report here the antiepileptic effects of diagnostic depth electrode implantation in a patient with formerly pharmacoresistant epilepsy who has remained seizure free for more than 4 years after invasive recordings without subsequent epilepsy surgery. ### History This 37-year-old woman was admitted to our hospital with a history of focal epileptic seizures since the age of 27 years. Habitual seizures consisted of a cephalic aura and complex partial seizures with behavioural arrest and manual automatisms; seizure frequency was 1 every 5–7 days. Secondarily generalised tonic–clonic seizures had occurred only three times. Pharmacotherapy with maximally tolerable doses of carbamazepine, valproate, phenytoin, oxcarbazepine, levetiracetam and lamotrigine in mono- and polytherapy was unable to control her complex partial seizures. She was thus considered a potential surgical candidate and underwent presurgical evaluation. ### Presurgical evaluation A comprehensive presurgical workup was performed, including high resolution MR imaging …

Cerebral metastasis of cervical uterine cancer: report of three cases

Cervical uterine cancer (CUC) spreads locally (pelvis and paraortic lymphnodes) or distantly (lungs, liver and bones). Metastasis to central nervous system (CNS) are rare. There are about 80 cases reported in the literature. Outcome is poor and survival varies from 3 to 6 months. Three cases of CNS metastasis from CUC are reported, one infratentorial and two supratentorials in location. In one patient, the initial manifestation was due to the cerebral lesion, a feature reported for the first time. All cases were treated by surgery, radiotherapy and/or chemotherapy. Clinical findings and treatment options of these rare lesions are reviewed.

Ventral extradural spinal meningeal cyst causing cord compression: Neurosurgical treatment

Spinal extradural meningeal cysts are typically formed by a thin fibrotic membranous capsule, macroscopically similar that of an arachnoid membrane, filled by cerebro spinal fluid and related to a nerve root or to the posterior midline. Ventral location is extremely rare and when it occurs they usually cause spinal cord herniation through the ventral dural gap. A 61 year-old man who began with a two years long history of insidious tetraparesis, spasticity and hyperreflexia in lower extremities, and flaccid atrophy of upper limbs, without sensory manifestations, is presented. Investigation through magnetic resonance imaging demonstrated an extensive spinal ventral extradural cystic collection from C6 to T11. The lesion was approached through a laminectomy and a cyst-peritoneal shunt was introduced. The cyst reduced in size significantly and the patient is asymptomatic over a 48 months follow-up. This is the first reported case of a spontaneous ventral extradural spinal meningeal cyst causing cord compression. Cyst-peritoneal shunt was effective in the treatment of the case and it should be considered in cases in which complete resection of the cyst is made more difficult or risky by the need of more aggressive surgical maneuvers.

Correlation of 18F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool

Background Magnetic resonance imaging (MRI) is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET), has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs) and histological diagnosis and grading has not yet been described. Objectives The aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm3), and to analyze the diagnostic value of PET using the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy. Patients and methods A total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study. Subsequently to diagnoses, all patients underwent a 18F-FET PET-guided stereotactic biopsy, using an original newly developed software module, which is presented here. Conventional MRI, stereotactic computed tomography series, and 18F-FET PET images were semiautomatically fused, and hot-spot detection was performed for target planning. UR was determined using the uptake value from the biopsy sites in relation to the contralateral frontal white matter. UR values ≥1.6 were considered positive for glioma. High-grade glioma (HGG) was suspected with URs ≥3.0, while low-grade glioma (LGG) was suspected with URs between 1.6 and 3.0. Stereotactic serial biopsies along the trajectory at multiple sites were performed in millimeter steps, and the FET URs for each site were correlated exactly with a panel of 27 different histopathological markers. Comparisons between FET URs along the biopsy trajectories and the histological diagnoses were made with Pearson product-moment correlation coefficients. Analysis of variance was performed to test for significant differences in maximum UR between different tumor grades. Results A total of 363 biopsy specimens were taken from 23 patients by stereotactic serial biopsies. Histological examination revealed eight patients (35%) with an LGG: one with a World Health Organization (WHO)-I lesion and seven with a WHO-II lesion. Thirteen (57%) patients revealed an HGG (two with a WHO-III and three with a WHO-IV tumor), and two patients (9%) showed a process that was neither HGG nor LGG (group X or no-grade group). The correlation matrix between histological findings and the UR revealed five strong correlations. Low cell density in tissue samples was found to have a significant negative correlation with the measured cortical uptake rate (r=−0.43, P=0.02), as well as moderate cell density (r=−0.48, P=0.02). Pathological patterns of proliferation (r=0.37, P=0.04), GFAP (r=0.37, P=0.04), and Olig2 (r=0.36, P=0.05) showed a significant positive correlation with cortical URs. Analysis of variance tests showed a significant difference between the LGG and the HGG groups (F=8.27, P<0.002), but no significant differences when differentiating between the X group and the HGG (P=0.2)/LGG (P=0.8) groups, nor between the no-grade group and the WHO-I group. Conclusion 18F-FET PET is a valuable tool, as it allows the differentiation of HGGs from LGGs. Its use is not limited to preoperative evaluation; it may also refine biopsy targeting and improve tumor delimitation for radiotherapy. Histology is still necessary, and remains the gold standard for definitive diagnosis of brain lesions.

Safety of hybrid electrodes for single-neuron recordings in humans.

BACKGROUND Intracranial in vivo recordings of individual neurons in humans are increasingly performed for a better understanding of the mechanisms of epileptogenesis and of the neurobiological basis of cognition. So far, information about the safety of stereotactic implantations and of magnetic resonance imaging (MRI) with hybrid depth electrodes is scarce. OBJECTIVE The aim of this study was to assess neurosurgical safety of implantations, recordings, and imaging using hybrid electrodes in humans. METHODS Perioperative and long-term safety of implantation of a total of 88 hybrid depth electrodes with integrated microwires was assessed retrospectively in 25 consecutive epilepsy patients who underwent implantation of electrodes from 2007 to 2011 based on electronically stored charts. Safety aspects of MRI are reported from both in vitro and in vivo investigations. Precision of electrode implantation is evaluated based on intraoperative computed tomography and pre- and postoperative MRI. RESULTS There was no clinically relevant morbidity associated with the use of hybrid electrodes in any of the patients. Precision of recordings from the targets aimed at was similar to that of standard depth electrodes. In vitro studies demonstrated the absence of relevant heating of hybrid electrodes with newly designed connectors with MRI at 1.5 T, corresponding to well-tolerated clinical MRI in patients. CONCLUSION Given the technical approach described here, precise targeting and safe use are possible with hybrid electrodes containing microwires for in vivo recording of human neuronal units.

Frame-based stereotactic neurosurgery in children under the age of seven: Freiburg University's experience from 99 consecutive cases

INTRODUCTION Stereotactic frame-based procedures proved to be precise, safe and are of widespread use among adult patients. Regarding pediatric patients few data is available, therefore the use of the stereotactic frame remains controversial in this population. This motivated us to report our experience in stereotactic procedures in the youngest patients and review the literature concerning this subject. METHODS All frame-based procedures performed in patients younger than seven years in the University of Freiburg during the last 10 years were retrospectively analyzed and discussed under the light of the current literature. RESULTS The studied population was composed of 72 patients under the age of seven (mean 3.4±2.1 years-old), in whom 99 stereotactic procedures were performed. Brain tumor was present in 60 patients, hydrocephalus in five, cystic lesions in three, intracranial abscess in three and epilepsy in one patient. Stereotactic surgery was performed in 36 cases for brachytherapy, in 29 for biopsy, in 20 cases for cyst puncture, in eight for stereotactically guided endoscopic ventriculostomy, in five for catheter placement and in one case for depth electrode insertion. The overall complication rate was 5%. There were three cases of pin penetration through the skull, one case of frame dislocation after extensive cyst drainage and two skull fractures. Neurologic deficit related to frame fixation was observed in none of the cases. In disagreement with other authors, no case of pin related infection, air embolism, hematoma or CSF leak was observed. CONCLUSION Frame-based stereotactic neurosurgery is a safe technique also in the youngest patients. Rather than the simple use of torque-limiting devices training and experience in the manual adjustment of the stereotactic frame in children have been proven to be crucial factors that contribute to reducing pin related complications.

Subthalamic nucleus lesion improves cell survival and functional recovery following dopaminergic cell transplantation in parkinsonian rats

Subthalamic nucleus (STN) modulation is currently the gold standard in the treatment of Parkinsons disease (PD) cases refractory to medication. Cell transplantation is a tissue‐restorative approach and is a promising strategy in the treatment of PD. One of the obstacles to overcome in cell therapy is the poor dopaminergic cell survival. Our experiment investigates the impact of a partial subthalamotomy prior to ventral mesencephalic (VM) embryonic cell transplantation on dopaminergic cell survival and functional outcome. Unilateral dopamine depletion was carried out in rats, via medial forebrain bundle (MFB) injection of 6‐hydroxydopamine, and half of the animals went on to receive unilateral excitotoxic lesions of the STN/Zone Incerta (ZI) causing partial lesion of these structures on the same side as the MFB lesion. All MFB‐lesioned animals, with or without the STN/ZI lesion, received striatal ipsilateral embryonic VM cell grafts. The data suggest that the STN/ZI lesion could boost the dopamine cell survival in the grafts by 2.6‐fold compared with the control grafted‐only group. Moreover, performance on the drug‐induced rotation and the spontaneous behavior tests were ameliorated on the STN/ZI‐lesioned group to a significantly greater extent than the grafted‐only group. These data suggest that the STN/ZI partial lesion optimized the striatal environment, promoting an improvement in cell survival. Further studies are needed to see whether the synergy between STN modulation via deep brain stimulation and cell therapy might have clinical applications in the management of PD.

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson’s disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft–host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions.

Modulation of excitability by continuous low- and high-frequency stimulation in fully hippocampal kindled rats

BACKGROUND Low- and high-frequency stimulation (LFS and HFS, respectively) have been, reported to modify seizure characteristics in rats. We here report effects of hippocampal LFS and HFS, applied at two or four sites in fully kindled rats. METHODS Rats were kindled through a hippocampal tetrode until the fully kindled state. Animals with, stable afterdischarge (AD) threshold were randomly assigned to 5 groups; stimulation at 1Hz (LFS) or, 130Hz (HFS) was continuously applied for 7 days at 2 or 4 intrahippocampal sites; a control, group received no stimulation. Four-contact stimulation was performed in a rotating fashion. Stimulation effects on AD threshold, AD duration and behavioral seizures were assessed. KEY FINDINGS Four-contact LFS consistently increased AD threshold for a period of 2 days to 2 weeks, whereas 4-contact HFS significantly decreased AD duration 24hours following the stimulation period. No significant AD modification was observed with either 2-contact stimulation paradigms. No, behavioral alteration occurred in any group. SIGNIFICANCE These findings suggest that effects of hippocampal stimulation depend on frequency and topography of stimulus application. LFS and HFS had anti-epileptic effect on afterdischarges when applied in a rotating pattern. This supports concepts on patterned stimulation to result in desynchronization and anti-kindling effects.

Measuring epileptogenicity in kainic acid injected rats

The present work aims at improving the validation of therapeutic approaches to treat temporal lobe epilepsy. Todays antiepileptic drugs perform only poorly for this form of epilepsy, and electrical stimulation might be an alternative for these patients. Finding the optimal stimulation parameters, however, is difficult as the underlying mechanisms, both of the disease and the stimulation procedure, and even the evaluation of the therapeutic effect are still poorly understood. Here we used a method to obtain a quantitative measure - the relative phase clustering index (rPCI) - of the epileptogenicity of a brain region in a simple and straightforward way.