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Albert Larbrisseau, Francois Renevey, Pierre Brochu, Michel Décarie, and Jean-Pierre Mathieu

✓ This is the first case report of an intraspinal cystic teratoma that manifested itself in recurrent episodes of chemical meningitis, with no sign of a space-occupying lesion.

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Taylor J. Abel, René Varela Osorio, Ricardo Amorim-Leite, Francois Mathieu, Philippe Kahane, Lorella Minotti, Dominique Hoffmann, and Stephan Chabardes

OBJECTIVE

Robot-assisted stereoelectroencephalography (SEEG) is gaining popularity as a technique for localization of the epileptogenic zone (EZ) in children with pharmacoresistant epilepsy. Here, the authors describe their frameless robot-assisted SEEG technique and report preliminary outcomes and relative complications in children as compared to results with the Talairach frame–based SEEG technique.

METHODS

The authors retrospectively analyzed the results of 19 robot-assisted SEEG electrode implantations in 17 consecutive children (age < 17 years) with pharmacoresistant epilepsy, and compared these results to 19 preceding SEEG electrode implantations in 18 children who underwent the traditional Talairach frame–based SEEG electrode implantation. The primary end points were seizure-freedom rates, operating time, and complication rates.

RESULTS

Seventeen children (age < 17 years) underwent a total of 19 robot-assisted SEEG electrode implantations. In total, 265 electrodes were implanted. Twelve children went on to have EZ resection: 4 demonstrated Engel class I outcomes, whereas 2 had Engel class II outcomes, and 6 had Engel class III–IV outcomes. Of the 5 patients who did not have resection, 2 underwent thermocoagulation. One child reported transient paresthesia associated with 2 small subdural hematomas, and 3 other children had minor asymptomatic intracranial hemorrhages. There were no differences in complication rates, rates of resective epilepsy surgery, or seizure freedom rates between this cohort and the preceding 18 children who underwent Talairach frame–based SEEG. The frameless robot-assisted technique was associated with shorter operating time (p < 0.05).

CONCLUSIONS

Frameless robot-assisted SEEG is a safe and effective means of identifying the EZ in children with pharmacoresistant partial epilepsy. Robot-assisted SEEG is faster than the Talairach frame–based method, and has equivalent safety and efficacy. The former, furthermore, facilitates more electrode trajectory possibilities, which may improve the localization of epileptic networks.

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Alain Pierre-Kahn, Jean-François Hirsch, Mathieu Vinchon, Christine Payan, Christian Sainte-Rose, Dominique Renier, Arielle Lelouch-Tubiana, and Jacques Fermanian

A study was made of 75 children treated between 1970 and 1990, with partial, subtotal, or total removal of three intrinsic and 72 exophytic or surface brain-stem tumors. In all cases, the goal of surgery was to remove as much tumor as possible. Extent of removal was defined according to data obtained from postoperative computerized tomography or magnetic resonance imaging, and was considered partial when only a small amount of tumor was removed, subtotal when a few cubic millimeters of tumor was left, and total when no residual tumor was seen on postoperative radiological investigations. An ultrasonic aspirator was used for the 43 most recent operations. Among tumor removals without the aspirator, 24 (75%) were partial, eight (25%) subtotal, and none total; with the use of the aspirator, the number of partial removals decreased to 44.5% while that of subtotal and total removals increased to 32% and 23.5%, respectively. There were 69 gliomas (92%) and 47 benign tumors (62.6%). Forty-nine patients were irradiated postoperatively, and 14 of the 23 patients whose benign tumors were removed totally or subtotally did not undergo irradiation.

This study showed that: 1) the overall prognosis of patients with malignant tumors was poor and was not improved by surgery; 2) the survival rate of those with benign tumors was significantly (p < 0.01) lower after partial removal than after total or subtotal removal (52% and 94%, respectively, at 5 years); 3) comparison of means and proportions (Student's and chi-squared tests) between benign and malignant tumors showed a significant difference relating to patient age (p < 0.03), peritumoral hypodensity (p < 0.001), and preoperative duration of symptoms (p < 0.001); 4) stepwise logistic regression analysis confirmed that two of these three variables were related to malignancy: namely, patient age at surgery (p < 0.03) and presence of peritumoral hypodensity (p < 0.001); and 5) routine postoperative irradiation was contraindicated after total or subtotal removal of benign tumors.

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Alexandrine Gagnon, Mathieu Laroche, David Williamson, Marc Giroux, Jean-François Giguère, and Francis Bernard

OBJECTIVE

After craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors’ objective was to describe the incidence and characteristics of brain hypoxia after craniectomy.

METHODS

The authors included 25 consecutive patients who underwent a craniectomy after traumatic brain injury or intracerebral hemorrhage and who were monitored afterward with a brain tissue oxygen pressure monitor.

RESULTS

The frequency of hypoxic values after surgery was 14.6% despite ICP being controlled. Patients had a mean of 18 ± 23 hypoxic episodes. Endotracheal (ET) secretions (17.4%), low cerebral perfusion pressure (10.3%), and mobilizing the patient (8.6%) were the most common causes identified. Elevated ICP was rarely identified as the cause of hypoxia (4%). No cause of cerebral hypoxia could be determined 31.2% of the time. Effective treatments that were mainly used included sedation/analgesia (20.8%), ET secretion suctioning (15.4%), and increase in fraction of inspired oxygen or positive end-expiratory pressure (14.1%).

CONCLUSIONS

Cerebral hypoxia is common after craniectomy, despite ICP being controlled. ET secretion and patient mobilization are common causes that are easily treatable and often not identified by standard monitoring. These results suggest that monitoring should be pursued even if ICP is controlled. The authors’ findings might provide a hypothesis to explain the poor functional outcome in the recent randomized controlled trials on craniectomy after traumatic brain injury where in which brain tissue oxygen pressure was not measured.

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Laura Dellazizzo, Simon-Pierre Demers, Emmanuel Charbonney, Virginie Williams, Karim Serri, Martin Albert, Jean-François Giguère, Mathieu Laroche, David Williamson, and Francis Bernard

OBJECTIVE

Avoiding decreases in brain tissue oxygenation (PbtO2) after traumatic brain injury (TBI) is important. How best to adjust PbtO2 remains unclear. The authors investigated the association between partial pressure of oxygen (PaO2) and PbtO2 to determine the minimal PaO2 required to maintain PbtO2 above the hypoxic threshold (> 20 mm Hg), accounting for other determinants of PbtO2 and repeated measurements in the same patient. They also explored the clinical utility of a novel concept, the brain oxygenation ratio (BOx ratio = PbtO2/PaO2) to detect overtreatment with the fraction of inspired oxygen (FiO2).

METHODS

A retrospective cohort study at an academic level 1 trauma center included 38 TBI patients who required the insertion of a monitor to measure PbtO2. Various determinants of PbtO2 were collected simultaneously whenever a routine arterial blood gas was drawn. A PbtO2/PaO2 ratio was calculated for each blood gas and plotted over time for each patient. All patients were managed according to a standardized clinical protocol. A mixed effects model was used to account for repeated measurements in the same patient.

RESULTS

A total of 1006 data points were collected. The lowest mean PaO2 observed to maintain PbtO2 above the ischemic threshold was 94 mm Hg. Only PaO2 and cerebral perfusion pressure were predictive of PbtO2 in multivariate analysis. The PbtO2/PaO2 ratio was below 0.15 in 41.7% of all measures and normal PbtO2 values present despite an abnormal ratio in 27.1% of measurements.

CONCLUSIONS

The authors’ results suggest that the minimal PaO2 target to ensure adequate cerebral oxygenation during the first few days after TBI should be higher than that suggested in the Brain Trauma Foundation guidelines. The use of a PbtO2/PaO2 ratio (BOx ratio) may be clinically useful and identifies abnormal O2 delivery mechanisms (cerebral blood flow, diffusion, and cerebral metabolic rate of oxygen) despite normal PbtO2.

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Dorian Chauvet, Laurent Marsac, Mathieu Pernot, Anne-Laure Boch, Rémy Guillevin, Najat Salameh, Line Souris, Luc Darrasse, Mathias Fink, Mickaël Tanter, and Jean-François Aubry

Object

This work aimed at evaluating the accuracy of MR-guided high-intensity focused ultrasound (MRgHIFU) brain therapy in human cadaver heads.

Methods

Eighteen heads of fresh human cadavers were removed with a dedicated protocol preventing intracerebral air penetration. The MR images allowed determination of the ultrasonic target: a part of the thalamic nucleus ventralis intermedius implicated in essential tremor. Osseous aberrations were corrected with simulation-based time reversal by using CT data from the heads. The ultrasonic session was performed with a 512-element phased-array transducer system operating at 1 MHz under stereotactic conditions with thermometric real-time MR monitoring performed using a 1.5-T imager.

Results

Dissection, imaging, targeting, and planning have validated the feasibility of this human cadaver model. The average temperature elevation measured by proton resonance frequency shift was 7.9°C ± 3°C. Based on MRI data, the accuracy of MRgHIFU is 0.4 ± 1 mm along the right/left axis, 0.7 ± 1.2 mm along the dorsal/ventral axis, and 0.5 ± 2.4 mm in the rostral/caudal axis.

Conclusions

Despite its limits (temperature, vascularization), the human cadaver model is effective for studying the accuracy of MRgHIFU brain therapy. With the 1-MHz system investigated here, there is millimetric accuracy.

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Gabriel Crevier-Sorbo, Tristan Brunette-Clément, Edgard Medawar, Francois Mathieu, Benjamin R. Morgan, Laureen D. Hachem, Michael C. Dewan, Aria Fallah, Alexander G. Weil, and George M. Ibrahim

OBJECTIVE

Epilepsy disproportionately affects low- and/or middle-income countries (LMICs). Surgical treatments for epilepsy are potentially curative and cost-effective and may improve quality of life and reduce social stigmas. In the current study, the authors estimate the potential need for a surgical epilepsy program in Haiti by applying contemporary epilepsy surgery referral guidelines to a population of children assessed at the Clinique d’Épilepsie de Port-au-Prince (CLIDEP).

METHODS

The authors reviewed 812 pediatric patient records from the CLIDEP, the only pediatric epilepsy referral center in Haiti. Clinical covariates and seizure outcomes were extracted from digitized charts. Electroencephalography (EEG) and neuroimaging reports were further analyzed to determine the prevalence of focal epilepsy or surgically amenable syndromes and to assess the lesional causes of epilepsy in Haiti. Lastly, the toolsforepilepsy instrument was applied to determine the proportion of patients who met the criteria for epilepsy surgery referral.

RESULTS

Two-thirds of the patients at CLIDEP (543/812) were determined to have epilepsy based on clinical and diagnostic evaluations. Most of them (82%, 444/543) had been evaluated with interictal EEG, 88% of whom (391/444) had abnormal findings. The most common finding was a unilateral focal abnormality (32%, 125/391). Neuroimaging, a prerequisite for applying the epilepsy surgery referral criteria, had been performed in only 58 patients in the entire CLIDEP cohort, 39 of whom were eventually diagnosed with epilepsy. Two-thirds (26/39) of those patients had abnormal findings on neuroimaging. Most patients (55%, 18/33) assessed with the toolsforepilepsy application met the criteria for epilepsy surgery referral.

CONCLUSIONS

The authors’ findings suggest that many children with epilepsy in Haiti could benefit from being evaluated at a center with the capacity to perform basic brain imaging and neurosurgical treatments.

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Mathieu Pernot, Jean-Francois Aubry, Mickael Tanter, Anne-Laure Boch, Fabrice Marquet, Michele Kujas, Danielle Seilhean, and Prof. Mathias Fink

Object

High-intensity focused ultrasonography is known to induce controlled and selective noninvasive destruction of tissues by focusing ultrasonic beams within organs, like a magnifying glass concentrating enough sunlight to burn a hole in paper. Such a technique should be highly interesting for the treatment of deep-seated lesions in the brain. Nevertheless, ultrasonic tissue ablation in the brain has long been hampered by the defocusing effect of the skull bone.

Methods

In this in vivo study, the authors used a high-power time-reversal mirror specially designed for noninvasive ultrasonic brain treatment to induce thermal lesions through the skulls of 10 sheep. The sheep were divided into three groups and, depending on group, were killed 1, 2, or 3 weeks after treatment. The thermal lesions were confirmed based on findings of posttreatment magnetic resonance imaging and histological examinations.

After treatment, the basic neurological functions of the animals were unchanged: the animals recovered from anesthesia without any abnormal delay and did not exhibit signs of paralysis or coma. No major behavioral change was observed.

Conclusions

The results provide striking evidence that noninvasive ultrasonographic brain surgery is feasible. Thus the authors offer a novel noninvasive method of performing local brain ablation in animals for behavioral studies. This technique may lead the way to noninvasive and nonionizing treatment of brain tumors and neurological disorders by selectively targeting intracranial lesions. Nevertheless, sheep do not represent a good functional model and extensive work will need to be conducted preferably on monkeys to investigate the effects of this treatment.

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Catherine Horodyckid, Michael Canney, Alexandre Vignot, Raphael Boisgard, Aurélie Drier, Gilles Huberfeld, Chantal François, Annick Prigent, Mathieu D. Santin, Clovis Adam, Jean-Claude Willer, Cyril Lafon, Jean-Yves Chapelon, and Alexandre Carpentier

OBJECTIVE

The main limitation to the efficacy of chemotherapy for brain tumors is the restricted access to the brain because of the limited permeability of the blood-brain barrier (BBB). Previous animal studies have shown that the application of pulsed ultrasound (US), in combination with the intravenous injection of microbubbles, can temporarily disrupt the BBB to deliver drugs that normally cannot reach brain tissue. Although many previous studies have been performed with external focused US transducers, the device described in the current work emits US energy using an unfocused transducer implanted in the skull thickness. This method avoids distortion of the US energy by the skull bone and allows for simple, repetitive, and broad disruption of the BBB without the need for MRI monitoring. The purpose of the present study was to determine if the BBB can be safely and repeatedly disrupted using such an implantable unfocused US device in a primate model.

METHODS

An 11.5-mm-diameter, 1-MHz, planar US device was implanted via a bur hole into the skull of 3 primates (2 Papio anubis [olive] baboons and 1 Macaca fascicularis [macaque]) for 4 months. Pulsed US sonications were applied together with the simultaneous intravenous injection of sulfur hexafluoride microbubbles (SonoVue) every 2 weeks to temporarily disrupt the BBB. In each primate, a total of 7 sonications were performed with a 23.2-msec burst length (25,000 cycles) and a 1-Hz pulse repetition frequency at acoustic pressure levels of 0.6–0.8 MPa. Potential toxicity induced by repeated BBB opening was analyzed using MRI, PET, electroencephalography (EEG), somatosensory evoked potential (SSEP) monitoring, behavioral scales, and histopathological analysis.

RESULTS

The T1-weighted contrast-enhanced MR images acquired after each sonication exhibited a zone of hypersignal underneath the transducer that persisted for more than 4 hours, indicating a broad region of BBB opening in the acoustic field of the implant. Positron emission tomography images with fluorine-18–labeled fluorodeoxyglucose (FDG) did not indicate any changes in the cerebral metabolism of glucose. Neither epileptic signs nor pathological central nerve conduction was observed on EEG and SSEP recordings, respectively. Behavior in all animals remained normal. Histological analysis showed no hemorrhagic processes, no petechia, and extravasation of only a few erythrocytes.

CONCLUSIONS

The studies performed confirm that an implantable, 1-MHz US device can be used to repeatedly open the BBB broadly in a large-animal model without inducing any acute, subacute, or chronic lesions.