P. Paquis

Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity, sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions. During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation (weekly frequency of attacks decrease >50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Tumorigenic Potential of miR‐18A* in Glioma Initiating Cells Requires NOTCH‐1 Signaling

Stem cell‐like properties of glioma initiating cells (GiCs) fuel glioblastoma (GBM) development by providing the different cell types that comprise the tumor. It is therefore likely that the molecular circuitries that regulate their decision to self‐renew or commit to a more differentiated state may offer targets for future innovative therapies. In previous micro‐RNA profiling studies to search for regulators of stem cell plasticity, we identified miR‐18a* as a potential candidate and its expression correlated with the stemness state. Here, using human GiCs we found that miR‐18a* expression promotes clonal proliferation in vitro and tumorigenicity in vivo. Mechanistically, ERK‐dependent induction of miR‐18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH, thus enhancing the level of activated NOTCH‐1. Activated NOTCH‐1 in turn is required for sustained ERK activation. This feed‐forward loop, driven by miR‐18a*, is required to turn on the SHH‐GLI‐NANOG network, essential for GiC self‐renewal. Hence, by tightly regulating expression of DLL3, miR‐18a* constitutes an important signaling mediator for fine tuning the level of GiC self‐renewal. STEM Cells2013;31:1252–1265

Biocomputing: Numerical simulation of glioblastoma growth and comparison with conventional irradiation margins

OBJECT Estimation of glioblastoma (GBM) growth patterns is of tremendous value in determining tumour margins for radiotherapy. We have previously developed a numerical simulation model for the pattern of spread of glioblastoma tumours. This model involved the creation of a digital atlas of the brain with elasticity and resistance-to-invasion values for specific brain structures and also included probable direction of tumour spread as estimated by Diffusion Tensor Imaging (DTI). The current study is aimed at comparing the outcome of such simulation with conventional irradiation margins currently in use. METHODS Actual patient data were used to simulate the direction of microscopic extension, using a variety of margin-, proliferation- and diffusion-rate scenarios to generate growth patterns, which were then compared with current standard radiotherapy margins. RESULTS Our patient growth pattern simulations showed microscopic invasion beyond irradiation margins for both combinations of high-diffusion/low-proliferation and low-diffusion/high-proliferation rate scenarios. The model also indicated that some healthy brain tissue that was projected to be safe from recurrence fell inside treatment margins. CONCLUSION These results may explain the current inadequacy of our treatment techniques in preventing locoregional recurrences of GBM.

Endodermal cyst of the foramen magnum: case report and review of the literature.

Abstract The majority of endodermal cysts occur in the cervicothoracic spine, ventral to the cord. Intracranial locations are rare. We report a case involving the foramen magnum in a 14-year-old child, which was an incidental finding following a traumatic head injury. A review of the literature revealed six other cases involving this same location. These lesions are asymptomatic for a long time, and may cause brain stem medullary compression. Treatment is surgical. Effective simple removal can be achieved by a posterior approach.

Dynamic Model of Communicating Hydrocephalus for Surgery Simulation

We propose a dynamic model of cerebrospinal fluid and intracranial pressure regulation. In this model, we investigate the coupling of biological parameters with a 3-D model, to improve the behavior of the brain in surgical simulators. The model was assessed by comparing the simulated ventricular enlargement with a patient case study of communicating hydrocephalus. In our model, cerebro-spinal fluid production-resorption system is coupled with a 3-D representation of the brain parenchyma. We introduce a new bi-phasic model of the brain (brain tissue and extracellular fluid) allowing for fluid exchange between the brain extracellular space and the venous system. The time evolution of ventricular pressure has been recorded on a symptomatic patient after closing the ventricular shunt. A finite element model has been built based on a computed tomography scan of this patient, and quantitative comparisons between experimental measures and simulated data are proposed

Ruptured intracranial aneurysms in the elderly

Spontaneous subarachnoid hemorrhage (SAH) is often a devastating condition and a significant cause of worldwide morbidity and mortality. Because the percentage of senior citizens is increasing in many countries and because of the increased incidence of SAH in elderly patients, ruptured intracranial aneurysm is an increasingly frequent pathology in western countries. Twenty years ago, older people were considered to have such a poor prognosis that they were frequently excluded from active treatment on the unique basis of their advanced age. Improving results published in recent studies showed that the classic fatalistic attitude associated with age and intracranial aneurysm (IA) should be reconsidered. Therefore, because of improvements in surgical results and neuro-intensive care, the appearance of interventional neuroradiology, and more aggressive rehabilitation programs, the management of ruptured IA in the elderly is changing. This article aims to review epidemiology, emphasize the specific aspects of the disease in the elderly, and present the current management of SAH in an elderly population.

Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth

Glioblastomas are incurable primary brain tumors that affect patients of all ages. The aggressiveness of this cancer has been attributed in part to the persistence of treatment-resistant glioblastoma stem-like cells. We have previously discovered the tumor-suppressor properties of the microRNA cluster miR-302-367, representing a potential treatment for glioblastoma. Here, we attempted to develop a cell-based therapy by taking advantage of the capability of glioma cells to secrete exosomes that enclose small RNA molecules. We engineered primary glioma cells to stably express the miR-302-367. Remarkably, these cells altered, in a paracrine-dependent manner, the expression of stemness markers, the proliferation and the tumorigenicity of neighboring glioblastoma cells. Further characterization of the secretome derived from miR-302-367 expressing cells showed that a large amount of miR-302-367 was enclosed in exosomes, which were internalized by the neighboring glioblastoma cells. This miR-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain.

Localisation sous-tentorielle d’une tumeur dysembryoplasique neuroépithéliale: À propos d’un cas

Neuroepithelial dysembryoplastic tumor (DNT) is usually considered as a supratentorial benign neoplasm. DNT of the posterior fossa is a very rare entity and only four previous cases were reported in the literature. We describe a case of a 26-Year-old woman presenting recurrent episodes of vertigo. Magnetic resonance imaging revealed four cystic lesions located in the cerebellum, hypointense on T1-weighted images and hyperintense on T2-weighted images, without gadolinium enhancement. After partial resection, histological examination showed small glial cells, oligodendrocytes-like, lying in an eosinophilic alveolar matrix with some floating neurons. Due to this specific glioneuronal element, the diagnosis of DNT was retained. We discuss the clinical and radiological particularities of this infratentorial location and compare our case with those previously described in the literature.Resume Les tumeurs dysembryoplasiques neuroepitheliales (DNT) sont generalement considerees comme des lesions benignes de localisation sus-tentorielle. Les DNT sous-tentorielles sont des entites rares et seulement 4 cas ont ete decrits dans la litterature. Nous rapportons le cas d’une femme de 26 ans presentant des vertiges paroxystiques. Le bilan d’imagerie par resonance magnetique revele quatre lesions kystiques cerebelleuses hypo-intenses en T1, hyperintenses en T2 et non rehaussees a l’injection de gadolinium. Apres resection partielle, l’etude anatomopathologique montre de petites cellules gliales oligodendrocytes-like agencees sur une matrice alveolaire eosinophile contenant de rares neurones. Cet element glioneuronal specifique fait poser le diagnostic de tumeur dysembryoplasique neuroepitheliale. Nous discutons des particularites cliniques et radiologiques de ces formes sous-tentorielles et comparons notre cas a ceux precedemment decrits dans la litterature.

Rosai-Dorfman disease causing spinal cord compression: case report.

OBJECTIVERosai-Dorfman disease is a rare idiopathic, histiocytic, proliferative disease characterized by massive, painless cervical lymphadenopathy. Extranodal involvement is rare and central nervous system involvement is unusual. We present a patient with Rosai-Dorfman disease with spinal cord compression. Very few cases have been reported in the literature. CLINICAL PRESENTATIONA 17-year-old man presented with a 1-month history of progressive fatigue of the legs. His medical history was significant for Rosai-Dorfman disease diagnosed 7 months earlier. Clinical examination was consistent with a pyramidal syndrome and proprioceptive disturbances on his lower limbs without sensory level. A magnetic resonance imaging scan revealed an intradural extramedullary space-occupying lesion at the T1-T4 level with dural insertion and spinal cord compression. INTERVENTIONA T1–T4 laminotomy was performed. Upon opening the dura, a reddish-gray mass was encountered, which encased the dorsal and lateral arachnoidal membrane. The lesion was relatively well circumscribed and was easily dissected from the underlying arachnoid. Pathological examination of the compressive soft tissue was consistent with Rosai-Dorfman disease. Postoperatively, the patient showed substantial improvement in neurological function. He was followed for 18 months with no complaints and no recurrence. CONCLUSIONNeurosurgeons should consider this rare etiology of spinal cord compression. They must be aware that this lesion can occur in front of an intraspinal lesion, mimic meningiomas, occur in young people, and can potentially be associated with other locations of disease, including intracranial lesions. Surgery is the treatment of choice.

Short-term restoration of facial sensory loss by motor cortex stimulation in peripheral post-traumatic neuropathic pain

We report a case in which motor cortex stimulation (MCS) improved neuropathic facial pain due to peripheral nerve injury and restored tactile and thermal sensory loss. A 66-year-old man developed intractable trigeminal neuropathic pain after trauma of the supraorbital branch of the Vth nerve, associated with tactile and thermal sensory loss in the painful area. MCS was performed using neuronavigation and transdural electric stimulation to localize the upper facial area on the motor cortex. One month after surgery, pain was decreased from 80/100 to 20/100 on visual analogic scale, and sensory discrimination improved in the painful area. Two months after surgery, quantitative sensory testing confirmed the normalization of thermal detection thresholds. This case showed that MCS could restore tactile and thermal sensory loss, resulting from peripheral nerve injury. Although the mechanisms leading to this effect remain unclear, this observation enhanced the hypothesis that MCS acts through modulation of the sensory processing.