Optimal hippocampal targeting in responsive neurostimulation for mesial temporal lobe epilepsy.

OBJECTIVE: The aim of this study was to identify features of responsive neurostimulation (RNS) lead configuration and contact placement associated with greater seizure reduction in mesial temporal lobe epilepsy (MTLE). METHODS: A single-center series of patients with MTLE treated with RNS were retrospectively analyzed to assess the relationship between anatomical targeting and seizure reduction. Targeting was determined according to both the preoperatively conceived lead configuration and the actual placement of RNS contacts. Three lead configurations were used: 1) single bilateral, with 1 depth lead in each hippocampus; 2) single unilateral, with 1 hippocampal depth lead and another implant outside the mesial temporal lobe; and 3) dual unilateral, with 2 leads in 1 hippocampus. Contact placement on postoperative imaging was measured according to the number of hippocampal contacts per targeted hippocampus (contact density) and per patient (contact count), distribution throughout the hippocampus, and proximity to the anteromedial hippocampus. RESULTS: Dual unilateral lead placement resulted in significantly higher hippocampal contact density compared with the single hippocampal approaches, but only showed a nonsignificant trend toward a higher rate of response. However, those patients with more than 4 contacts in a single hippocampus, achievable only with dual unilateral leads, had a significantly higher rate of response. The higher likelihood of response was poorly explained by more widespread hippocampal coverage, but well correlated with proximity to the anteromedial hippocampus. CONCLUSIONS: Dual unilateral hippocampal implantation increased RNS contact density in patients with unilateral MTLE, which contributed to improved outcomes, not by stimulating more of the hippocampus, but instead by being more likely to stimulate a latent subtarget in the anterior hippocampus. It remains to be explored whether a single electrode targeted selectively to this region would also result in improved outcomes.

Teaching NeuroImage: Unilateral Primary Angiitis of the CNS.

A 48-year-old woman was referred with an 18-year history of focal-onset seizures. She also reported years-long slowly progressive right-sided weakness that was corroborated on examination. Repeated brain MRIs over 15 years showed multifocal left hemispheric T2 fluid-attenuated inversion recovery-hyperintense lesions with patchy enhancement and microhemorrhages, no diffusion restriction, and a left cerebellar infarct (Figure 1, A-F). Only 2 nonspecific white matter lesions were seen contralaterally, indicating largely unihemispheric disease. Differential diagnosis included unilateral primary angiitis of the CNS (PACNS), Rasmussen encephalitis, and myelin oligodendrocyte glycoprotein antibody-associated disease.1 Serum and CSF testing for autoimmune, infectious, and malignant etiologies and whole-body fluorodeoxyglucose-PET, whole-exome genetic sequencing, and MR vessel-wall imaging were nondiagnostic. Brain biopsy revealed vasculitis (Figure 2, A-F), and the patient was diagnosed with unilateral PACNS. Treatment with mycophenolate mofetil has been initiated. Unilateral PACNS is a rare unihemispheric disease characterized by an indolent course and seizures, recognition of which is critical to accurate diagnosis.1,2.

Spinal Nerve Root Stimulation for Chronic Pain: A Systematic Review.

OBJECTIVE: Spinal cord stimulation (SCS) has been used as a minimally invasive and effective treatment modality for various chronic pain disorders, with the main target being stimulation of the dorsal columns; however, certain neuropathic pain areas involve dermatomes that are suboptimally covered by SCS. Stimulation of the spinal nerve roots has the advantage of targeting one or several dermatomes at the same time. The aim of this systematic review is to investigate the efficacy of spinal nerve root stimulation (SNRS) for chronic pain disorders. MATERIALS AND METHODS: A detailed literature review was performed through the Ovid Embase and MEDLINE data bases in addition to reference searching. Gray literature was included by searching through common search engines using a simplified search strategy. Studies included were focused on adult patients (aged >18 years), diagnosis of chronic pain syndrome (including but not limited to complex regional pain syndrome, persistent spinal pain syndrome, neuropathic pain secondary to trauma or infection, postherpetic pain, and cancer pain). Patients must have undergone SNRS insertion, with ≥six months of documented pain intensity scores on follow-up. RESULTS: A total of 40 studies underwent full text review, and 13 articles were included in final analysis. Mean preoperative pain intensity was 8.14 ± 0.74 on the visual analog scale, whereas mean postoperative pain intensity at one year was 3.18 ± 1.44. Of 119 patients, 83 (70%) achieved ≥50% reduction in pain intensity after SNRS, whereas 36 (30%) achieved <50% reduction in pain intensity. Only three studies assessed changes in analgesia medication dose and reported morphine equivalent doses varied by case series. Overall, there was a trend toward a reduction in analgesia medications in the postoperative period. CONCLUSIONS: SNRS led to a mean 44% reduction in pain intensity, with a low level of certainty. In addition, there is some evidence to suggest that using SNRS is associated with reduced use of analgesics, including morphine and gabapentin.

Lack of spontaneous typical seizures during intracranial monitoring with stereo-electroencephalography.

OBJECTIVE: In the presurgical evaluation of patients with drug-resistant epilepsy (DRE), occasionally, patients do not experience spontaneous typical seizures (STS) during a stereo-electroencephalography (SEEG) study, which limits its effectiveness. We sought to identify risk factors for patients who did not have STS during SEEG and to analyze the clinical outcomes for this particular set of patients. METHODS: We conducted a retrospective analysis of all patients with DRE who underwent depth electrode implantation and SEEG recordings between January 2013 and December 2018. RESULTS: SEEG was performed in 155 cases during this period. 11 (7.2%) did not experience any clinical seizures (non-STS group), while 143 experienced at least one patient-typical seizure during admission (STS group). No significant differences were found between STS and non-STS groups in terms of patient demographics, lesional/non-lesional epilepsy ratio, pre-SEEG seizure frequency, number of ASMs used, electrographic seizures or postoperative seizure outcome in those who underwent resective surgery. Statistically significant differences were found in the average number of electrodes implanted (7.0 in the non-STS group vs. 10.2 in STS), days in Epilepsy Monitoring Unit (21.8 vs. 12.8 days) and the number of cases that underwent resective surgery following SEEG (27.3% vs. 60.8%), respectively. The three non-STS patients (30%) who underwent surgery, all had their typical seizures triggered during ECS studies. Three cases were found to have psychogenic non-epileptic seizures. None of the patients in the non-STS group were offered neurostimulation devices. Five of the non-STS patients experienced transient seizure improvement following SEEG. SIGNIFICANCE: We were unable to identify any factors that predicted lack of seizures during SEEG recordings. Resective surgery was only offered in cases where ECS studies replicated patient-typical seizures. Larger datasets are required to be able to identify factors that predict which patients will fail to develop seizures during SEEG.

Involvement of the posterior cingulate gyrus in temporal lobe epilepsy: A study using stereo-EEG.

OBJECTIVE: To analyze the involvement of the posterior cingulate gyrus (PCG) during mesial temporal lobe seizures (MTLS). METHODS: We retrospectively reviewed the stereo-EEG (SEEG) recordings of patients with MTLS performed in our institution from February 2013 to December 2020. Only patients who had electrode implantation in the PCG were included. Patients with lesions that could potentially alter the seizure spread pathways were excluded. We assessed the propagation patterns of MTLS with respect to the different structures sampled. RESULTS: Nine of 97 patients who had at least one seizure originating in the mesial temporal region met the inclusion criteria. A total of 174 seizures were analyzed. The PCG was the first site of propagation in most of the cases (8/9 patients and 77.5% of seizures, and 7/8 patients and 65.6% of seizures after excluding an outlier patient). The fastest propagation times were towards the contralateral mesial temporal region and ipsilateral PCG. Seven patients underwent standard anterior temporal lobectomy and, of these, all but one were Engel 1 at last follow up. CONCLUSION: We found the PCG to be the first propagation site of MTLS in this group of patients. These results outline the relevance of the PCG in SEEG planning strategies. Further investigations are needed to corroborate whether fast propagation to the PCG predicts a good surgical outcome.

A population-averaged structural connectomic brain atlas dataset from 422 HCP-aging subjects.

Population-averaged brain atlases, that are represented in a standard space with anatomical labels, are instrumental tools in neurosurgical planning and the study of neurodegenerative conditions. Traditional brain atlases are primarily derived from anatomical scans and contain limited information regarding the axonal organization of the white matter. With the advance of diffusion MRI that allows the modeling of fiber orientation distribution (FOD) in the brain tissue, there is an increasing interest for a population-averaged FOD template, especially based on a large healthy aging cohort, to offer structural connectivity information for connectomic surgery and analysis of neurodegeneration. The dataset described in this article contains a set of multi-contrast structural connectomic MRI atlases, including T1w, T2w, and FOD templates, along with the associated whole brain tractograms. The templates were made using multi-contrast group-wise registration based on 3T MRIs of 422 Human Connectome Project in Aging (HCP-A) subjects. To enhance the usability, probabilistic tissue maps and segmentation of 22 subcortical structures are provided. Finally, the subthalamic nucleus shown in the atlas is parcellated into sensorimotor, limbic, and associative sub-regions based on their structural connectivity to facilitate the analysis and planning of deep brain stimulation procedures. The dataset is available on the OSF Repository: https://osf.io/p7syt.

Magnetic resonance imaging datasets with anatomical fiducials for quality control and registration.

Tools available for reproducible, quantitative assessment of brain correspondence have been limited. We previously validated the anatomical fiducial (AFID) placement protocol for point-based assessment of image registration with millimetric (mm) accuracy. In this data descriptor, we release curated AFID placements for some of the most commonly used structural magnetic resonance imaging datasets and templates. The release of our accurate placements allows for rapid quality control of image registration, teaching neuroanatomy, and clinical applications such as disease diagnosis and surgical targeting. We release placements on individual subjects from four datasets (N = 132 subjects for a total of 15,232 fiducials) and 14 brain templates (4,288 fiducials), totalling more than 300 human rater hours of annotation. We also validate human rater accuracy of released placements to be within 1 - 2 mm (using more than 45,000 Euclidean distances), consistent with prior studies. Our data is compliant with the Brain Imaging Data Structure allowing for facile incorporation into neuroimaging analysis pipelines.

Surgical Interventions Targeting the Nucleus Caudalis for Craniofacial Pain: A Systematic and Historical Review.

INTRODUCTION: Craniofacial pain is a prevalent group of conditions, and when refractory to conventional treatments, it poses a significant burden. The last decade has seen a renewed interest in the multimodal management of pain. Interventions targeting the nucleus caudalis (NC) of the trigeminocervical complex have been available as a treatment option since the 1930s, yet evidence for efficacy remains limited. MATERIALS AND METHODS: We present a systematic review of the literature providing a historical perspective on interventions targeting the NC leading up to the present. We examine the various intervention techniques, clinical indications, and procedural efficacy. A novel outcome-reporting scheme was devised to enable comparison among studies owing to historically variable reporting methods. RESULTS: A review of the literature revealed 33 retrospective studies published over the last 80 years, reporting on 827 patients. The most common technique was the open NC dorsal root entry zone nucleotomy/tractotomy; however, there has been an emergence of novel approaches such as endoscopic and spinal cord stimulation in the last ten years. Regardless of intervention technique or preoperative diagnosis, 87% of patients showed improvement with treatment. CONCLUSIONS: The literature surrounding NC intervention techniques is reviewed. Recent advancements and the wide range of craniofacial pain syndromes for which these interventions show potential efficacy are discussed. New and less invasive techniques continue to emerge as putative therapeutic options. However, prospective studies are lacking. Furthermore, the evidence supporting even well-established techniques remains of poor quality. Future work should be prospective, use standard outcome reporting, and address efficacy comparisons between intervention type and preoperative diagnosis.

Automated hippocampal unfolding for morphometry and subfield segmentation with HippUnfold.

Like neocortical structures, the archicortical hippocampus differs in its folding patterns across individuals. Here, we present an automated and robust BIDS-App, HippUnfold, for defining and indexing individual-specific hippocampal folding in MRI, analogous to popular tools used in neocortical reconstruction. Such tailoring is critical for inter-individual alignment, with topology serving as the basis for homology. This topological framework enables qualitatively new analyses of morphological and laminar structure in the hippocampus or its subfields. It is critical for refining current neuroimaging analyses at a meso- as well as micro-scale. HippUnfold uses state-of-the-art deep learning combined with previously developed topological constraints to generate uniquely folded surfaces to fit a given subject's hippocampal conformation. It is designed to work with commonly employed sub-millimetric MRI acquisitions, with possible extension to microscopic resolution. In this paper, we describe the power of HippUnfold in feature extraction, and highlight its unique value compared to several extant hippocampal subfield analysis methods.

Mapping the subcortical connectome using in vivo diffusion MRI: Feasibility and reliability.

Tractography combined with regions of interest (ROIs) has been used to non-invasively study the structural connectivity of the cortex as well as to assess the reliability of these connections. However, the subcortical connectome (subcortex to subcortex) has not been comprehensively examined, in part due to the difficulty of performing tractography in this complex and compact region. In this study, we performed an in vivo investigation using tractography to assess the feasibility and reliability of mapping known connections between structures of the subcortex using the test-retest dataset from the Human Connectome Project (HCP). We further validated our observations using a separate unrelated subjects dataset from the HCP. Quantitative assessment was performed by computing tract densities and spatial overlap of identified connections between subcortical ROIs. Further, known connections between structures of the basal ganglia and thalamus were identified and visually inspected, comparing tractography reconstructed trajectories with descriptions from tract-tracing studies. Our observations demonstrate both the feasibility and reliability of using a data-driven tractography-based approach to map the subcortical connectome in vivo.

Application of the anatomical fiducials framework to a clinical dataset of patients with Parkinson's disease.

Establishing spatial correspondence between subject and template images is necessary in neuroimaging research and clinical applications such as brain mapping and stereotactic neurosurgery. Our anatomical fiducial (AFID) framework has recently been validated to serve as a quantitative measure of image registration based on salient anatomical features. In this study, we sought to apply the AFIDs protocol to the clinic, focusing on structural magnetic resonance images obtained from patients with Parkinson's disease (PD). We confirmed AFIDs could be placed to millimetric accuracy in the PD dataset with results comparable to those in normal control subjects. We evaluated subject-to-template registration using this framework by aligning the clinical scans to standard template space using a robust open preprocessing workflow. We found that registration errors measured using AFIDs were higher than previously reported, suggesting the need for optimization of image processing pipelines for clinical grade datasets. Finally, we examined the utility of using point-to-point distances between AFIDs as a morphometric biomarker of PD, finding evidence of reduced distances between AFIDs that circumscribe regions known to be affected in PD including the substantia nigra. Overall, we provide evidence that AFIDs can be successfully applied in a clinical setting and utilized to provide localized and quantitative measures of registration error. AFIDs provide clinicians and researchers with a common, open framework for quality control and validation of spatial correspondence and the location of anatomical structures, facilitating aggregation of imaging datasets and comparisons between various neurological conditions.

Effects of MP2RAGE B1+ sensitivity on inter-site T1 reproducibility and hippocampal morphometry at 7T.

Most neuroanatomical studies are based on T1-weighted MR images, whose intensity profiles are not solely determined by the tissue's longitudinal relaxation times (T1), but also affected by varying non-T1 contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameter choices - e.g., to emphasize intracortical myelin-dependent contrast variations - can substantially impact image quality and cortical analyses through remnants of B1+-related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B1+ insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal morphometry. The latter remained unexplored initially, but can provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B1+ inhomogeneities have a considerably variable effect on cortical T1 estimates, as well as on hippocampal morphometry depending on the MP2RAGE setup. While T1 differed substantially across datasets initially, we show the inter-site T1 comparability improves after correcting for the spatially varying B1+ field using a separately acquired Sa2RAGE B1+ map. Finally, removal of B1+ residuals affects hippocampal volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid). Taken together, we show that the choice of MP2RAGE parameters can impact T1 comparability across sites and present evidence that hippocampal segmentation results are modulated by B1+ inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols, as well as (2) acquisition of a B1+ map to correct MP2RAGE data for potential B1+ variations to allow comparison across datasets.

Image Guidance in Deep Brain Stimulation Surgery to Treat Parkinson's Disease: A Comprehensive Review.

Deep brain stimulation (DBS) is an effective therapy as an alternative to pharmaceutical treatments for Parkinson's disease (PD). Aside from factors such as instrumentation, treatment plans, and surgical protocols, the success of the procedure depends heavily on the accurate placement of the electrode within the optimal therapeutic targets while avoiding vital structures that can cause surgical complications and adverse neurologic effects. Although specific surgical techniques for DBS can vary, interventional guidance with medical imaging has greatly contributed to the development, outcomes, and safety of the procedure. With rapid development in novel imaging techniques, computational methods, and surgical navigation software, as well as growing insights into the disease and mechanism of action of DBS, modern image guidance is expected to further enhance the capacity and efficacy of the procedure in treating PD. This article surveys the state-of-the-art techniques in image-guided DBS surgery to treat PD, and discusses their benefits and drawbacks, as well as future directions on the topic.

Direct visualization and characterization of the human zona incerta and surrounding structures.

The zona incerta (ZI) is a small gray matter region of the deep brain first identified in the 19th century, yet direct in vivo visualization and characterization has remained elusive. Noninvasive detection of the ZI and surrounding region could be critical to further our understanding of this widely connected but poorly understood deep brain region and could contribute to the development and optimization of neuromodulatory therapies. We demonstrate that high resolution (submillimetric) longitudinal (T1) relaxometry measurements at high magnetic field strength (7 T) can be used to delineate the ZI from surrounding white matter structures, specifically the fasciculus cerebellothalamicus, fields of Forel (fasciculus lenticularis, fasciculus thalamicus, and field H), and medial lemniscus. Using this approach, we successfully derived in vivo estimates of the size, shape, location, and tissue characteristics of substructures in the ZI region, confirming observations only previously possible through histological evaluation that this region is not just a space between structures but contains distinct morphological entities that should be considered separately. Our findings pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional and neuromodulatory investigation.

Stereoelectroencephalography Versus Subdural Strip Electrode Implantations: Feasibility, Complications, and Outcomes in 500 Intracranial Monitoring Cases for Drug-Resistant Epilepsy.

BACKGROUND: Both stereoelectroencephalography (SEEG) and subdural strip electrodes (SSE) are used for intracranial electroencephalographic recordings in the invasive investigation of patients with drug-resistant epilepsy. OBJECTIVE: To compare SEEG and SSE with respect to feasibility, complications, and outcome in this single-center study. METHODS: Patient characteristics, periprocedural parameters, complications, and outcome were acquired from a pro- and retrospectively managed databank to compare SEEG and SSE cases. RESULTS: A total of 500 intracranial electroencephalographic monitoring cases in 450 patients were analyzed (145 SEEG and 355 SSE). Both groups were of similar age, gender distribution, and duration of epilepsy. Implantation of each SEEG electrode took 13.9 ± 7.6 min (20 ± 12 min for each SSE; P < .01). Radiation exposure to the patient was 4.3 ± 7.7 s to a dose area product of 14.6 ± 27.9 rad*cm2 for SEEG and 9.4 ± 8.9 s with 21 ± 22.4 rad*cm2 for SSE (P < .01). There was no difference in the length of stay (12.2 ± 7.2 and 12 ± 6.3 d). The complication rate was low in both groups. No infections were seen in SEEG cases (2.3% after SSE). The rate of hemorrhage was 2.8% for SEEG and 1.4% for SSE. Surgical outcome was similar. CONCLUSION: SEEG allows targeting deeply situated foci with a non-inferior safety profile to SSE and seizure outcome comparable to SSE.

Robot-Assisted Insular Depth Electrode Implantation Through Oblique Trajectories: 3-Dimensional Anatomical Nuances, Technique, Accuracy, and Safety.

BACKGROUND: The insula is a deep cortical structure that has renewed interest in epilepsy investigation. Invasive EEG recordings of this region have been challenging. Robot-assisted stereotactic electroencephalography has improved feasibility and safety of such procedures. OBJECTIVE: To describe technical nuances of three-dimensional (3D) oblique trajectories for insular robot-assisted depth electrode implantation. METHODS: Fifty patients who underwent robot-assisted depth electrode implantation between June 2017 and December 2018 were retrospectively analyzed. Insular electrodes were implanted through oblique, orthogonal, or parasagittal trajectories. Type of trajectories, accuracy, number of contacts within insular cortex, imaging, and complication rates were analyzed. Cadaveric and computerized tomography/magnetic resonance imaging 3D reconstructions were used to visualize insular anatomy and the technical implications of oblique trajectories. RESULTS: Forty-one patients (98 insular electrodes) were included. Thirty (73.2%) patients had unilateral insular coverage. Average insular electrodes per patient was 2.4. The mean number of contacts was 7.1 (SD ± 2.91) for all trajectories and 8.3 (SD ± 1.51) for oblique insular trajectories. The most frequently used was the oblique trajectory (85 electrodes). Mean entry point error was 1.5 mm (0.2-2.8) and target error was 2.4 mm (0.8-4.0), 2.0 mm (1.1-2.9) for anterior oblique and 2.8 mm (0.8-4.9) for posterior oblique trajectories. There were no complications related to insular electrodes. CONCLUSION: Oblique trajectories are the preferred method for insular investigation at our institution, maximizing the number of contacts within insular cortex without traversing through sulci or major CSF fissures. Robot-assisted procedures are safe and efficient. 3D understanding of the insula's unique anatomical features can help the surgeon to improve targeting of this structure.

An accurate registration of the BigBrain dataset with the MNI PD25 and ICBM152 atlases.

Brain atlases that encompass detailed anatomical or physiological features are instrumental in the research and surgical planning of various neurological conditions. Magnetic resonance imaging (MRI) has played important roles in neuro-image analysis while histological data remain crucial as a gold standard to guide and validate such analyses. With cellular-scale resolution, the BigBrain atlas offers 3D histology of a complete human brain, and is highly valuable to the research and clinical community. To bridge the insights at macro- and micro-levels, accurate mapping of BigBrain and established MRI brain atlases is necessary, but the existing registration is unsatisfactory. The described dataset includes co-registration of the BigBrain atlas to the MNI PD25 atlas and the ICBM152 2009b atlases (symmetric and asymmetric versions) in addition to manual segmentation of the basal ganglia, red nucleus, amygdala, and hippocampus for all mentioned atlases. The dataset intends to provide a bridge between insights from histological data and MRI studies in research and neurosurgical planning. The registered atlases, anatomical segmentations, and deformation matrices are available at: https://osf.io/xkqb3/ .

Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada.

In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.

Énoncé de position quant à l'utilisation du cannabis médical dans le traitement de l'épilepsie. L'utilisation du cannabis à des fins récréatives a été légalisée au Canada en octobre 2018. Parallèlement à ce changement de politique, de récentes publication visant à évaluer l'efficacité du cannabis dans le traitement de l'épilepsie, de même qu'une sensibilisation médiatique accrue en ce qui concerne son utilisation, ont eu pour effet d'augmenter l'intérêt du grand public à son égard. Le Comité médical thérapeutique de la Ligue canadienne contre l'épilepsie (LCCE), de concert avec un groupe multidisciplinaire d'experts et des représentants de l'Alliance canadienne de l'épilepsie, a ainsi élaboré un énoncé de position en ce qui regarde l'utilisation du cannabis médical dans le traitement de l'épilepsie. Cet article entend donc aborder le cadre légal qui prévaut actuellement au Canada et examiner de récentes publications s'étant penchées sur le profil sécuritaire et sur l'efficacité du cannabis. De plus, nous voulons apporter un éclairage au sujet des aspects cliniques dont il faudrait tenir compte au moment d'envisager l'utilisation du cannabis à des fins médicales.