Role of the pedunculopontine nucleus in controlling gait and sleep in normal and parkinsonian monkeys.

Patients with Parkinson's disease (PD) develop cardinal motor symptoms, including akinesia, rigidity, and tremor, that are alleviated by dopaminergic medication and/or subthalamic deep brain stimulation. Over the time course of the disease, gait and balance disorders worsen and become resistant to pharmacological and surgical treatments. These disorders generate debilitating motor symptoms leading to increased dependency, morbidity, and mortality. PD patients also experience sleep disturbance that raise the question of a common physiological basis. An extensive experimental and clinical body of work has highlighted the crucial role of the pedunculopontine nucleus (PPN) in the control of gait and sleep, and its potential major role in PD. Here, we summarise our investigations in the monkey PPN in the normal and parkinsonian states. We first examined the anatomy and connectivity of the PPN and the cuneiform nucleus which both belong to the mesencephalic locomotor region. Second, we conducted experiments to demonstrate the specific effects of PPN cholinergic lesions on locomotion in the normal and parkinsonian monkey. Third, we aimed to understand how PPN cholinergic lesions impair sleep in parkinsonian monkeys. Our final goal was to develop a novel model of advanced PD with gait and sleep disorders. We believe that this monkey model, even if it does not attempt to reproduce the exact human disease with all its complexities, represents a good biomedical model to characterise locomotion and sleep in the context of PD.

In Vivo Measurement of Brain Tumor Elasticity Using Intraoperative Shear Wave Elastography.

Purpose: Objective Shear wave elastography (SWE) enabled living tissue assessment of stiffness. This is routinely used for breast, thyroid and liver diseases, but there is currently no data for the brain. We aim to characterize elasticity of normal brain parenchyma and brain tumors using SWE. Materials and Methods: Patients with scheduled brain tumor removal were included in this study. In addition to standard ultrasonography, intraoperative SWE using an ultrafast ultrasonic device was used to measure the elasticity of each tumor and its surrounding normal brain. Data were collected by an investigator blinded to the diagnosis. Descriptive statistics, box plot analysis as well as intraoperator and interoperator reproducibility analysis were also performed. Results: 63 patients were included and classified into four main types of tumor: meningiomas, low-grade gliomas, high-grade gliomas and metastasis. Young's Modulus measured by SWE has given new insight to differentiate brain tumors: 33.1 ±â€Š5.9 kPa, 23.7 ±â€Š4.9 kPa, 11.4 ±â€Š3.6 kPa and 16.7 ±â€Š2.5 kPa, respectively, for the four subgroups. Normal brain tissue has been characterized by a reproducible mean stiffness of 7.3 ±â€Š2.1 kPa. Moreover, low-grade glioma stiffness is different from high-grade glioma stiffness (p = 0.01) and normal brain stiffness is very different from low-grade gliomas stiffness (p < 0.01). Conclusion: This study demonstrates that there are significant differences in elasticity among the most common types of brain tumors. With intraoperative SWE, neurosurgeons may have innovative information to predict diagnosis and guide their resection.

Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Imaging findings of intraventricular and ependymal lesions.

Intraventricular and ependymal lesions comprise a wide spectrum of tumoral, cystic, vascular, infectious and inflammatory disorders. With respect to tumoral and cystic diseases, the location, age and CT and MRI patterns are the main factors for diagnosis. The MRI findings of infectious diseases are supported by the clinical history, immune status and laboratory findings. Intracranial associated lesions may be very helpful for the diagnosis of Sturge-Weber, subependymal giant cell astrocytoma and systemic diseases, such as sarcoidosis and histiocytosis. Intraventricular vascular lesions are rare but present typical features on neuroimaging. The aim of this review is to provide a detailed description of these disorders with an emphasis on the key imaging findings and to generate a narrow differential diagnosis. We present a diagnostic approach based on the solid or cystic aspect of the intraventricular focal mass, its origin from the ventricular wall or choroid plexus and its location within the ventricular system. We also propose a differential diagnosis for ependymal dissemination: the ependymal enhancement may be due to ventriculitis from adjacent parenchymal lesions, the ependymal spread of tumors or infectious or inflammatory/systemic diseases.

Massive stroke in a patient with pituitary apoplexy, cervical carotid artery stenosis and hypotension.

We report a case of massive cerebral infarct in the early stage of pituitary apoplexy. The case is unique because the stroke was delayed and occurred only after the patient developed severe arterial hypotension superimposed on a tandem internal carotid artery stenosis by both the sellar mass on the siphon and an unknown homolateral atheromatous cervical lesion. Illustrated with MRI and specifically by diffusion-weighted imaging, this case reinforces the idea that a low apparent diffusion coefficient in a non-enhancing sellar mass may indicate the presence of pituitary apoplexy and help in the early adequate management of such patients.

[Optochiasmal cavernoma: a rare cause of unilateral visual loss]. / Baisse visuelle rapide unilatérale associée à un cavernome optochiasmatique.

INTRODUCTION: Optic pathways cavernomas are rare vascular hamartomas that can present either with an acute chiasmal syndrome or slowly progressive visual loss. OBSERVATION: A 29-year-old patient presented with mild unilateral visual loss of rapid onset and monocular left temporal hemianopia. MRI disclosed a heterogenous enhancing optochiasmal lesion. Work-up found no evidence for an inflammatory, infectious or tumoral disease and therefore a neurosurgical approach of the lesion allowed diagnosis of cavernoma, confirmed by pathological examination. Successful resection resulted in partial recovery of the visual field. CONCLUSION: Optochiasmal cavernomas are rare, removal can improve visual outcome.

[Anaesthesia and Parkinson's disease]. / Anesthésie et maladie de Parkinson.

OBJECTIVE: The purpose of this review is to draw up a statement on current knowledge available on perioperative management of Parkinson's disease patients. STUDY DESIGN: Review. DATA SYNTHESIS: In France, approximately 150,000 persons suffer from Parkinson's disease, a neurodegenerative disorder of central nervous system. Parkinson's disease results in selective and irreversible loss of dopaminergic neurons in the substantia nigra pars compacta. Medications based on dopaminergic drugs are used to control motor symptoms and improve motor function. Development of surgical approach, especially deep brain stimulation, has revolutionized the medical management of many patients with Parkinson's disease. Anesthesia of these patients remains a challenge for the clinician. The aim of this review is to describe anaesthetic considerations of patients with Parkinson's disease and to discuss management of antiparkinsonians medications during the perioperative period.

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology.

Subthalamic stimulation and neuronal activity in the substantia nigra in Parkinson's disease.

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.

Tourette's syndrome and deep brain stimulation.

In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.