Preservation of frontal white matter tracts in ventricular surgery: favoring an anterior interhemispheric transcallosal approach vs a transcortical transfrontal transventricular approach.

Secondary to the creation of a surgical corridor and retraction, white matter tracts degenerate, causing long-term scarring with potential neurological consequences. Third and lateral ventricle tumors require surgery that may lead to cognitive impairment. Our objective is to compare the long-term consequences of a transcortical transfrontal approach and an interhemispheric transcallosal approach on corpus callosum and frontal white matter tracts degeneration. Surgical patients with ventricular tumor accessible through both approaches were included and clinico-radiological data were retrospectively analyzed. The primary endpoint was the callosotomy length at 3-month post-operative T1 MRI, corrected by the extension of the tumor and the use of neuronavigation. Secondary outcomes included perioperative criteria such as bleeding, use of retractors and duration, FLAIR hypersignal on 3-month MRI, and re-do surgeries. To assess white matter tract interruption, 3-month FLAIR hypersignal was superposed to a tractography atlas. Seventy patients were included, 57 (81%) in the transfrontal group and 13 (19%) in the interhemispheric group. There was no difference in the mean callosotomy length on 3-month MRI (12.3 mm ± 5.60 transfrontal vs 11.7 mm ± 3.92 interhemispheric, p = 0.79) on univariate and multivariate analyses. The callosotomy length was inferior by - 3.13 mm for tumors located exclusively in the third ventricle (p = 0.016), independent of the approach. Retractors were used more often in transfrontal approaches (60% vs 33%, p < 0.001). The extent of frontal FLAIR hypersignal was higher after transfrontal approach (14.1 mm vs 0.525 mm, p < 0.001), correlated to the use of retractors (p < 0.05). After the interhemispheric approach, no tract other than corpus callosum was interrupted, whereas, after the transfrontal approach, frontal arcuate fibers and projections from the thalamus were interrupted in all patients, the cingulum in 19 (33%), the superior fronto-occipital fasciculus in 15 (26%), and the superior longitudinal fasciculus in 2 (3%). Transfrontal and interhemispheric approaches to the third and lateral ventricles both lead to the same long-term damage to the corpus callosum, but the transfrontal approach interrupts several white matter tracts essential to cognitive tasks such as attention and planning, even in the non-dominant hemisphere. These results encourage all neurosurgeons to be familiar with both approaches and favor the interhemispheric approach when both can give access to the tumor with a comparable risk. Neuropsychological studies are necessary to correlate these anatomical findings to cognitive outcomes.

Interhemispheric transcallosal approach: going further based on the vascular anatomy.

Preserving cortical frontal bridging veins draining into the superior sagittal sinus is a factor of good neurological outcome in anterior interhemispheric transcallosal approaches, classically performed to reach intraventricular tumors. Challenging the idea that veins are utterly variable, we propose a statistical analysis of 100 selective cerebral angiographies to determine where to place the craniotomy in order to expose the most probable vein-free area. The mean distance to the first pre-coronal vein was 6.66 cm (± 1.73, 1.80 to 13.00) and to the first post-coronal vein 0.94 cm (± 0.92, 0 to 3.00) (p < 0.001). The probability of absence of bridging veins was 92.0% at 4 cm anterior to the coronal suture versus 37.5% at 1 cm and 12.5% at 2 cm posteriorly. The length of the surgical corridor (distance between the first pre-coronal and post-coronal vein) was 7.60 cm (± 1.72, 3.00 to 14.10). Overall, the ideal centering point of the craniotomy was 2.86 cm (± 1.08, - 0.65 to 6.50) ahead of the coronal suture. The mean number of veins within 6 cm behind the coronal suture was 8.47 (± 2.11, from 3 to 15) versus 0.530 (± 0.82, from 0 to 3) ahead of the coronal suture (p < 0.001). These findings support a purely pre-coronal 5 cm craniotomy for interhemispheric approaches.

Surgical treatment of hypothalamic hamartomas.

Hypothalamic hamartomas are aberrant masses, composed of abnormally distributed neurons and glia. Along endocrine and cognitive symptoms, they may cause epileptic seizures, including the specific gelastic and dacrystic seizures. Surgery is the treatment of drug-resistant hamartoma epilepsy, with associated positive results on endocrine, psychiatric, and cognitive symptoms. Recently, alternatives to open microsurgical treatment have been proposed. We review these techniques and compare their efficacy and safety. Open resection or disconnection of the hamartoma, either through pterional, transcallosal, or transventricular approach, leads to good epileptological control, but its high complication rate, up to 30%, limits its indications. The purely cisternal peduncular forms remain the only indication of open, pterional approach, while other strategies have been developed to overcome the neurological, endocrine, behavioral, or cognitive complications. Laser and radiofrequency thermocoagulation-based disconnection through robot-guided stereo-endoscopy has been proposed as an alternative to open microsurgical resection and stereotactic destruction. The goal is to allow safe and complete disconnection of a possibly complex attachment zone, through a single intraparenchymal trajectory which allows multiple laser or radiofrequency probe trajectory inside the ventricle. The efficacy was high, with 78% of favorable outcome, and the overall complication rate was 8%. It was especially effective in patients with isolated gelastic seizures and pure intraventricular hamartomas. Stereotactic radiosurgery has proved as efficacious and safer than open microsurgery, with around 60% of seizure control and a very low complication rate. Multiple stereotactic thermocoagulation showed very interesting results with 71% of seizure freedom and 2% of permanent complications. Stereotactic laser interstitial thermotherapy (LiTT) seems as effective as open microsurgery (from 76 to 81% of seizure freedom) but causes up to 20% of permanent complications. This technique has however been highly improved by targeting only the epileptogenic onset zone in the hamartoma, as shown on preoperative functional MRI, leading to an improvement of epilepsy control by 45% (92% of seizure freedom) with no postoperative morbidity. All these results suggest that the impact of the surgical procedure does not depend on purely technical matters (laser vs radiofrequency thermocoagulation or stereotactic vs robot-guided stereo-endoscopy) but relies on the understanding of the epileptic network, including inside the hamartoma, the aim being to plan an effective disconnection or lesion of the epileptogenic part while sparing the adjacent functional structures.

Vertical parasagittal hemispherotomy: a case report of postoperative mesio-temporal seizures via amygdalofugal pathway.

Vertical parasagittal hemispherotomy (VPH) is a well-established surgical treatment which is proposed for children with widespread unilateral onset of intractable epileptic seizures. VPH allows to disconnect from a vertical transventricular approach all white matter fibers of the hemisphere around a central core including the thalamus. We present the case of a girl who underwent VPH for hemimegalencephaly in early infancy. Postoperatively, she developed unexpected seizures of mesio-temporal origin. Stereo-EEG provided arguments for an amygdalar origin. High-resolution MRI with tractography confirmed the presence of the amygdalo-fugal pathway to be responsible of epileptic discharges propagation. She became seizure-free after temporal resection.

Could propranolol be beneficial in adult cerebral cavernous malformations?

Surgery is the only therapeutic option for cerebral cavernous malformations (CCM) and is proposed, whenever possible, after haemorrhagic events, neurological symptoms, or epilepsy, radiosurgery being a controversial alternative in some cases. However, there is no treatment for non-accessible lesions, such as brainstem CCM, multiple CCM, or those located in functional areas. Propranolol, a non-selective beta-blocker used as first-line treatment for infantile haemangiomas, has proved spectacularly effective in a few cases of adult patients with CCM. We herein review the histological, in vitro data and clinical findings that support the idea of propranolol as a potential treatment for CCM. Since one retrospective study has not been conclusive, we support the idea that prospective trials are necessary.

Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with focal epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Despite the increasing number of studies reporting results of stereo-electroencephalography (SEEG)-guided radiofrequency-thermocoagulation (SEEG-guided RF-TC) in the treatment of patients with drug-resistant focal epilepsy, the exact efficacy of this approach remains unclear. The seizure-freedom rate varies greatly across studies and the factors associated with efficacy have not been formally investigated. METHODS: All prospective or retrospective studies reporting efficacy and/or safety of SEEG-guided RF-TC in patients with drug-resistant focal epilepsy were included. The primary outcome was the seizure-free rate 1 year after the procedure. Secondary outcomes were (1) the responder rate 1 year after the procedure and (2) the proportion of patients with permanent neurologic deficit 1 year after the procedure. Each outcome was assessed in all patients and in 4 groups of patients defined by the etiology of epilepsy. Each outcome was pooled using inverse variance weighting, logit transformation of proportion, and a random-effects model. RESULTS: No prospective study was identified and a total of 6 retrospective studies, reporting efficacy and safety data of 296 patients, were included. The pooled rate of permanent neurologic deficit was 2.5% (95% confidence interval [CI] 1.2%-5.3%), without heterogeneity across studies. In contrast, both the seizure-free and responder rates varied greatly across studies, and statistical heterogeneity was high. The pooled seizure-free and responder rates were 23% (95% CI 8%-50%) and 58% (95% CI 36%-77%), respectively. Both for the seizure-free and responder rates, the greatest efficacy was observed in patients with periventricular nodular heterotopia and the lowest in patients with normal magnetic resonance imaging (MRI) findings. SIGNIFICANCE: SEEG-guided RF-TC is a safe procedure with low risk of complications. In contrast, the level of evidence regarding its efficacy remains low. Better identification of factors associated with seizure outcome are needed.

Task-induced gamma band effect in type II focal cortical dysplasia: An exploratory study.

OBJECTIVE: Few data are available about the functionality of type II focal cortical dysplasia (FCD). Identification of high-frequency activities (HFAs) induced by cognitive tasks has been proposed as an additional way to map cognitive functions in patients undergoing presurgical evaluation using stereoelectroencephalography (SEEG). However, the repetitive subcontinuous spiking pattern which characterizes type II FCD might limit the reliability of this approach, and its feasibility in these patients remains to be evaluated. METHODS: Seven patients whose magnetic resonance imaging (MRI) data, SEEG data, and/or pathological data were consistent with the diagnosis of type II FCD were included. All patients performed standardized cognitive tasks specifically designed to map task-induced increase of HFA (50 Hz to 150 Hz) at the recorded sites. Electrode contacts which showed an interictal SEEG pattern typical of type II FCD were considered to be localized within the FCD. A site was considered responsive if it was significantly different from baseline in at least one cognitive task. RESULTS: Three of the seven patients (43%) had significant task-induced increase of HFA in the FCD for a total of 15 sites with an interictal SEEG pattern typical of type II FCD. These sites were always localized at the external border of the FCD whereas no HFA response was in the core of FCD. In three of the four other patients, a significant task-induced increase of HFA was observed in a cortical site immediately adjacent to the dysplastic cortex. SIGNIFICANCE: Detection of task-induced HFA remains feasible despite the repetitive subcontinuous spiking pattern which characterizes type II FCD. Depending on the localization of the FCD, some sites of the dysplastic cortex were included in large-scale functional networks. However, these sites were always those closest to the nondysplastic cortex suggesting that persistence of cortical functions might be restricted to a limited part of the FCD.

Incomplete copolymer degradation of in situ chemotherapy.

In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery. Eleven months later, a third surgery was performed, revealing unexpected incomplete degradation of the wafer. 1H-Nuclear Magnetic Resonance was performed to compare this wafer to pure BCNU and to an unused copolymer wafer. In the used wafer, peaks corresponding to hydrophobic units of the excipient were no longer noticeable, whereas peaks of the hydrophilic units and traces of BCNU were still present. These surprising results could be related to the formation of a hydrophobic membrane around the wafer, thus interfering with the expected diffusion and degradation processes. The clinical benefit of carmustine wafers in addition to the standard radio-chemotherapy remains limited, and in vivo behavior of this treatment is not completely elucidated yet. We found that the wafer may remain after several months. Alternative strategies to deal with the blood-brain barrier, such as drug-loaded liposomes or ultrasound-opening, must be explored to offer larger drug diffusion or allow repetitive delivery.

Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

OBJECTIVE: To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. METHODS: We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. RESULTS: The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. SIGNIFICANCE: Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery.

Stereo electroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in drug-resistant focal epilepsy: Results from a 10-year experience.

OBJECTIVE: Stereo electroencephalography (SEEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has been proposed since 2004 as a possible treatment of some focal drug-resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG-guided RF-TC. METHODS: Over a 10-year period, 162 patients with drug-resistant focal epilepsy were eligible for SEEG-guided RF-TG during phase II invasive investigation by SEEG. All follow-up and safety data were collected prospectively. The primary outcome was seizure freedom at 2 months and at 1 year after SEEG-guided RF-TC. Secondary outcomes were the responders' rate (patient with at least 50% decrease in seizure frequency) and their long-term follow-up. RESULTS: Twenty-five percent of patients were seizure-free at 2 months and 7% at 1 year. We reported 67% of responders at 2 months and 48% at 1 year; 58% of responders maintained their status during the long-term follow-up. The seizure outcome was significantly better when the SEEG-guided RF-TC involved the occipital region (p = 0.007). When surgery followed an SEEG-guided RF-TC, the positive predictive value of being a responder 2 months after an SEEG-guided RF-TC and to be Engel's class I or II after surgery was 93%. We reported 1.1% of permanent deficit and 2.4% of transient side effects. SIGNIFICANCE: Our results, gathered in a large population over a 10-year period, confirm that SEEG-guided RF-TC is a safe technique, being efficient in many cases. More than two thirds of patients showed a short-term improvement, and almost half of them were responders at 1-year follow-up. The technique appears to be especially interesting for limited epileptic zone inaccessible to surgery and when epilepsy is related to a large unilateral network (network disruption by multiple RF-TC). Furthermore, SEEG-guided RF-TC effect is a predictor of outcome after conventional cortectomy in patients eligible for surgery.

Neuroplasticity and the brain connectome: what can Jean Talairach's reflections bring to modern psychosurgery?

Contrary to common psychosurgical practice in the 1950s, Dr. Jean Talairach had the intuition, based on clinical experience, that the brain connectome and neuroplasticity had a role to play in psychosurgery. Due to the remarkable progress of pharmacology at that time and to the technical limits of neurosurgery, these concepts were not put into practice. Currently, these concepts are being confirmed by modern techniques such as neuroimaging and computational neurosciences, and could pave the way for therapeutic innovation in psychiatry. Psychosurgery commonly uses a localizationist approach, based on the idea that a lesion to a specific area is responsible for a deficit opposite to its function. To psychosurgeons such as Walter Freeman, who performed extensive lesions causing apparently inevitable deficit, Talairach answered with clinical data: complex psychic functions cannot be described that simply, because the same lesion does not provoke the same deficit in different patients. Moreover, cognitive impairment did not always follow efficacious psychosurgery. Talairach suggested that selectively destructing part of a network could open the door to a new organization, and that early psychotherapy could encourage this psychoplasticity. Talairach did not have the opportunity to put these concepts into practice in psychiatric diseases because of the sudden availability of neuroleptics, but connectomics and neuroplasticity gave rise to major advances in intraparenchymal neurosurgery, from epilepsy to low-grade glioma. In psychiatry, alongside long-standing theories implicating focal lesions and diffuse pathological processes, neuroimaging techniques are currently being developed. In mentally healthy individuals, combining diffusion tensor imaging with functional MRI, magnetoencephalography, and electroencephalography allows the determination of a comprehensive map of neural connections in the brain on many spatial scales, the so-called connectome. Ultimately, global neurocomputational models could predict physiological activity, behavior, and subjective feeling, and describe neuropsychiatric disorders. Connectomic studies comparing psychiatric patients with controls have already confirmed the early intuitions of Talairach. As a striking example, massive dysconnectivity has been found in schizophrenia, leading some authors to propose a "dysconnection hypothesis." Alterations of the connectome have also been demonstrated in obsessive-compulsive disorder and depression. Furthermore, normalization of the functional dysconnectivity has been observed following clinical improvement in several therapeutic interventions, from psychotherapy to pharmacological treatments. Provided that mental disorders result from abnormal structural or functional wiring, targeted psychosurgery would require that one be able: 1) to identify the pathological network involved in a given patient; 2) to use neurostimulation to safely create a reversible and durable alteration, mimicking a lesion, in a network compatible with neuroplasticity; and 3) to predict which functional lesion would result in adapted neuronal plasticity and/or to guide neuronal plasticity to promote recovery. All these conditions, already suggested by Talairach, could now be achievable considering modern biomarkers and surgical progress.

Prediction of anaplastic transformation in low-grade oligodendrogliomas based on magnetic resonance spectroscopy and 1p/19q codeletion status.

The aim of this study was to assess whether combining multimodal magnetic resonance imaging (MRI) with the determination of the 1p/19q codeletion status could improve the ability to predict anaplastic transformation in low-grade oligodendrogliomas. Twenty patients with grade II oligodendrogliomas were followed-up using multimodal MR [proton MR spectroscopy (MRS), perfusion, and conventional MR imaging]. All patients diagnoses were histologically proven, and 1p/19q codeletion status was analyzed for all patients. Median follow-up was 30.5 ± 11.4 months. Anaplastic transformation was observed in six patients. The only MRI feature that was associated with anaplastic transformation was an elevation of the choline/creatine ratio >2.4 which was observed in 4 out of 6 patients with anaplastic transformation versus 1 out of 14 patients without anaplastic transformation. In patients without 1p/19q codeletion, an elevation of the choline/creatine ratio >2.4 was associated with the occurrence of anaplastic transformation in all cases (4 out of 4 patients), with a mean time of 12 months. In contrast, in patients with a 1p/19q codeletion, no anaplastic transformation was observed in the patient who had an elevation of >2.4 of the choline/creatine ratio and two patients demonstrated an anaplastic transformation without any elevation of this ratio.Prospective validation in a larger series is needed, yet the present study suggests that combining data from in vivo proton MRS and genetic analysis could be a promising strategy to predict time to anaplastic transformation at the individual level in patients with low-grade oligodendrogliomas and may help deciding when chemotherapy and/or radiotherapy should be initiated in these tumors.

Stereoelectroencephalography-guided radiofrequency thermocoagulation.

Within the neurosurgeon's armamentarium, stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) is an elegant tool to manage epilepsy in selected cases. This technique can 1) be curative when targeting small-volume ictal onset zones, 2) be used as a diagnostic tool by observing the consequences of coagulation on seizures or by recording the epileptic network in SEEG, and 3) offer palliative treatment through multiple lesions within a wide epileptic network. It is performed on awake patients, under continuous neurological evaluation, while monitoring impedance, time, and energy delivered. It could offer highly favorable outcomes in some cases, as in periventricular nodular heterotopia where 81% of patients are responders.

Case report: Simultaneous measurement of intracranial pressure and lumbar intrathecal pressure during epidural patch therapy for treating spontaneous intracranial hypotension syndrome. Spontaneous intracranial hypotension or spontaneous intraspinal hypovolume?

Objectives: Spontaneous intracranial hypotension (SIH) is frequently complicated by subacute subdural hematoma (SDH) and more rarely by bilateral thalamic ischemia. Here, we report a case of SIH-related SDH treated with three epidural patches (EPs), with follow-up of the intracranial pressure and lumbar intrathecal pressure. Methods: A 46-year-old man presented bilateral thalamic ischemia, then a growing SDH. After failure of urgent surgical evacuation, he underwent three saline EPs, two dynamic myelography examinations and one digital subtraction angiography-phlebography examination. However, because of no dural tear and no obstacle to the venous drainage of the vein of Galen, no therapeutic procedure was available, and the patient died. Results: The case exhibited a progressive increase in the transmission of lumbar intrathecal pressure to intracranial pressure during the three EPs. The EPs may have successfully treated the SIH, but the patient did not recover consciousness because of irreversible damage to both thalami. Conclusion: Clinicians should be aware of the bilateral thalamic ischemia picture that may be the presenting sign of SIH. Moreover, the key problem in the pathophysiology of SIH seems to be intraspinal and intracranial volumes rather than pressures. Therefore, intracranial hypotension syndrome might actually be an intraspinal hypovolume syndrome.

Differential cortical layer engagement during seizure initiation and spread in humans.

Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this study, we used laminar arrays of micro-electrodes to simultaneously record the local field potentials and multi-unit neural activities across the six layers of the neocortex during focal seizures in humans. We found that, within the ictal onset zone, the discharges generated during a seizure consisted of current sinks and sources only within the infra-granular and granular layers. Outside of the seizure onset zone, ictal discharges reflected current flow in the supra-granular layers. Interestingly, these patterns of current flow evolved during the course of the seizure - especially outside the seizure onset zone where superficial sinks and sources extended into the deeper layers. Based on these observations, a framework describing cortical-cortical dynamics of seizures is proposed with implications for seizure localization, surgical targeting, and neuromodulation techniques to block the generation and propagation of seizures.