White matter tracts and executive functions: a review of causal and correlation evidence.

Executive functions are high-level cognitive processes involving abilities such as working memory/updating, set-shifting and inhibition. These complex cognitive functions are enabled by interactions among widely distributed cognitive networks, supported by white matter tracts. Executive impairment is frequent in neurological conditions affecting white matter; however, whether specific tracts are crucial for normal executive functions is unclear. We review causal and correlation evidence from studies that used direct electrical stimulation during awake surgery for gliomas, voxel-based and tract-based lesion-symptom mapping, and diffusion tensor imaging to explore associations between the integrity of white matter tracts and executive functions in healthy and impaired adults. The corpus callosum was consistently associated with all executive processes, notably its anterior segments. Both causal and correlation evidence showed prominent support of the superior longitudinal fasciculus to executive functions, notably to working memory. More specifically, strong evidence suggested that the second branch of the superior longitudinal fasciculus is crucial for all executive functions, especially for flexibility. Global results showed left lateralization for verbal tasks and right lateralization for executive tasks with visual demands. The frontal aslant tract potentially supports executive functions, however, additional evidence is needed to clarify whether its involvement in executive tasks goes beyond the control of language. Converging evidence indicates that a right-lateralized network of tracts connecting cortical and subcortical grey matter regions supports the performance of tasks assessing response inhibition, some suggesting a role for the right anterior thalamic radiation. Finally, correlation evidence suggests a role for the cingulum bundle in executive functions, especially in tasks assessing inhibition. We discuss these findings in light of current knowledge about the functional role of these tracts, descriptions of the brain networks supporting executive functions and clinical implications for individuals with brain tumours.

Automatic gait events detection with inertial measurement units: healthy subjects and moderate to severe impaired patients.

BACKGROUND: Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed for the automatic detection of gait events (GEs). While many of them have achieved high levels of efficiency in healthy subjects, detecting GEs in highly degraded gait from moderate to severely impaired patients remains a challenge. In this paper, we aim to present a method for improving GE detection from IMU recordings in such cases. METHODS: We recorded 10-meter gait IMU signals from 13 healthy subjects, 29 patients with multiple sclerosis, and 21 patients with post-stroke equino varus foot. An instrumented mat was used as the gold standard. Our method detects GEs from filtered acceleration free from gravity and gyration signals. Firstly, we use autocorrelation and pattern detection techniques to identify a reference stride pattern. Next, we apply multiparametric Dynamic Time Warping to annotate this pattern from a model stride, in order to detect all GEs in the signal. RESULTS: We analyzed 16,819 GEs recorded from healthy subjects and achieved an F1-score of 100%, with a median absolute error of 8 ms (IQR [3-13] ms). In multiple sclerosis and equino varus foot cohorts, we analyzed 6067 and 8951 GEs, respectively, with F1-scores of 99.4% and 96.3%, and median absolute errors of 18 ms (IQR [8-39] ms) and 26 ms (IQR [12-50] ms). CONCLUSIONS: Our results are consistent with the state of the art for healthy subjects and demonstrate a good accuracy in GEs detection for pathological patients. Therefore, our proposed method provides an efficient way to detect GEs from IMU signals, even in degraded gaits. However, it should be evaluated in each cohort before being used to ensure its reliability.

A Machine Learning Pipeline for Gait Analysis in a Semi Free-Living Environment.

This paper presents a novel approach to creating a graphical summary of a subject's activity during a protocol in a Semi Free-Living Environment. Thanks to this new visualization, human behavior, in particular locomotion, can now be condensed into an easy-to-read and user-friendly output. As time series collected while monitoring patients in Semi Free-Living Environments are often long and complex, our contribution relies on an innovative pipeline of signal processing methods and machine learning algorithms. Once learned, the graphical representation is able to sum up all activities present in the data and can quickly be applied to newly acquired time series. In a nutshell, raw data from inertial measurement units are first segmented into homogeneous regimes with an adaptive change-point detection procedure, then each segment is automatically labeled. Then, features are extracted from each regime, and lastly, a score is computed using these features. The final visual summary is constructed from the scores of the activities and their comparisons to healthy models. This graphical output is a detailed, adaptive, and structured visualization that helps better understand the salient events in a complex gait protocol.

Peripheral neuropathies after BRAF and/or MEK inhibitor treatment: A pharmacovigilance study.

Reports suggested the potential occurrence of peripheral neuropathies (PN) in patients treated with BRAF (BRAFi) and/or MEK inhibitors (MEKi) for BRAF-activated tumours. We aimed to better characterize these PN. We queried the French pharmacovigilance database for all cases of PN attributed to BRAFi and/or MEKi. Fifteen patients were identified. Two main clinical PN phenotypes were seen. Six patients presented a length-dependent, axonal polyneuropathy: symptoms were mostly sensory and affecting the lower limbs; management and outcome were variable. Nine patients developed a demyelinating polyradiculoneuropathy: symptoms affected the four limbs and included hypoesthesia, weakness and ataxia; cranial nerves were involved in four cases; most patients received intravenous immunoglobulins or glucocorticoids, with variable outcome; one patient was rechallenged with a different BRAFi/MEKi combination with a rapid relapse in symptoms. In conclusion, patients under BRAFi/MEKi therapy may develop treatment-induced PN. Two main phenotypes can occur: a symmetric, axonal, length-dependent polyneuropathy and a demyelinating polyradiculoneuropathy.

Leukoencephalopathy with transient splenial lesions related to 5-fluorouracil or capecitabine.

BACKGROUND: 5-Fluorouracil (5-FU) and its oral prodrug capecitabine have been rarely but consistently associated with acute central nervous system toxicity, including transient leukoencephalopathies involving the splenium of the corpus callosum. METHODS: We performed a retrospective search in the French Pharmacovigilance database (FPDB) (January 1985-July 2020) for adult patients affected by solid cancers who developed acute toxic leukoencephalopathies with splenial lesions following treatment with 5-FU or capecitabine. A comprehensive review of the literature helped to circumstantiate our findings. RESULTS: Our research in the FPDB identified six patients who, within 3 days from their first cycle of 5-FU or capecitabine, developed acute neurological symptoms, including gait ataxia (n = 4), dysarthria (n = 3), dysmetria (n = 2), headache (n = 2), and confusion (n = 2). Brain magnetic resonance imaging (MRI) showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities in the corpus callosum, with diffusion restriction and no contrast enhancement, generally accompanied by additional alterations in the bilateral supratentorial white matter (n = 5). All patients discontinued the agent supposedly responsible for the toxicity and experienced full recovery after a median of 8.5 days from symptom onset. Control MRI showed a progressive normalization of acute MRI abnormalities. Literature review identified 26 cases with similar clinical and paraclinical characteristics. A single patient from the literature resumed 5-FU at a lower dose, with no recurrent toxicity. CONCLUSIONS: 5-FU and capecitabine might be responsible for acute leukoencephalopathies with transient splenial lesions that are generally reversible upon drug discontinuation. Resuming the agent responsible for toxicity might be feasible in selected cases, after having excluded dihydropyrimidine dehydrogenase deficiency, if expected benefits outweigh the risks.

Guillain-Barré Syndrome During Platinum-Based Chemotherapy: A Case Series and Review of the Literature.

Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non-dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. IMPLICATIONS FOR PRACTICE: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.

Sensitivity of the Montreal Cognitive Assessment in screening for cognitive impairment in patients with newly diagnosed high-grade glioma.

INTRODUCTION: Cognitive impairment is frequent in patients with high-grade glioma and requires cognitive follow-up. Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) have been used to assess cognition in these patients. Here we assessed the sensitivity of the MoCA in screening for cognitive impairment in a cohort of 156 patients with newly-diagnosed high-grade glioma, after surgery and before radiochemotherapy. METHODS: We assessed cognitive performance with the MoCA and a neuropsychological battery. Cognitive scores were analyzed in terms of a previously validated framework designed to control false positives and data for 1003 control participants from the GRECOGVASC study. After comparison of performance on the tests, we used stepwise logistic regression to produce a cognitive summary score from the neuropsychological battery. Then we analyzed sensitivity and specificity of the MoCA with receiver operator characteristic (ROC) curve analysis. RESULTS: Both raw and adjusted MoCA scores showed only moderate sensitivity. The area under the ROC curve was 0.759 (95% CI 0.703-0.815) for the raw score and 0.788 (95% CI 0.734-0.842) for the adjusted score. Optimal discrimination was obtained with a raw score ≤ 25 (sensitivity: 0.526; specificity: 0.832; positive predictive value: 0.2; negative predictive value: 0.96) and an adjusted score - 0.603 (sensitivity: 0.716; specificity: 0.768; positive predictive value: 0.24; negative predictive value: 0.96). CONCLUSION: The moderate sensitivity of MoCA indicates that it is not a suitable screening tool for detecting cognitive impairment in patients with newly-diagnosed high-grade glioma.

Correction to: Effect of vibration characteristics and vibror arrangement on the tactile perception of the upper arm in healthy subjects and upper limb amputees.

The original article [1] contained an error whereby the captions to Fig. 3 and Fig. 8 were mistakenly interchanged.

The Use of Inertial Measurement Units for the Study of Free Living Environment Activity Assessment: A Literature Review.

This article presents an overview of fifty-eight articles dedicated to the evaluation of physical activity in free-living conditions using wearable motion sensors. This review provides a comprehensive summary of the technical aspects linked to sensors (types, number, body positions, and technical characteristics) as well as a deep discussion on the protocols implemented in free-living conditions (environment, duration, instructions, activities, and annotation). Finally, it presents a description and a comparison of the main algorithms and processing tools used for assessing physical activity from raw signals.

Non-Linear Template-Based Approach for the Study of Locomotion.

The automatic detection of gait events (i.e., Initial Contact (IC) and Final Contact (FC)) is crucial for the characterisation of gait from Inertial Measurements Units. In this article, we present a method for detecting steps (i.e., IC and FC) from signals of gait sequences of individuals recorded with a gyrometer. The proposed approach combines the use of a dictionary of templates and a Dynamic Time Warping (DTW) measure of fit to retrieve these templates into input signals. Several strategies for choosing and learning the adequate templates from annotated data are also described. The method is tested on thirteen healthy subjects and compared to gold standard. Depending of the template choice, the proposed algorithm achieves average errors from 0.01 to 0.03 s for the detection of IC, FC and step duration. Results demonstrate that the use of DTW allows achieving these performances with only one single template. DTW is a convenient tool to perform pattern recognition on gait gyrometer signals. This study paves the way for new step detection methods: it shows that using one single template associated with non-linear deformations may be sufficient to model the gait of healthy subjects.

Patients' and physicians' interpretation of chemotherapy-induced peripheral neurotoxicity.

To test if and how chemotherapy-induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI-PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation ("impossible") generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%-65% of patients; 76%-78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%-56% of them. In Group 3 strength reduction was observed in 49%-50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.

Effect of vibration characteristics and vibror arrangement on the tactile perception of the upper arm in healthy subjects and upper limb amputees.

BACKGROUND: Vibrotactile stimulation is a promising venue in the field of prosthetics to retrain sensory feedback deficits following amputation. Discrimination is well established at the forearm level but not at the upper arm level. Moreover, the effects of combining vibration characteristics such as duration and intensity has never been investigated. METHOD: We conducted experiments on spatial discrimination (experiment 1) and tactile intensity perception (experiment 2), using 9 combinations of 3 intensities and 3 durations of vibror stimulations device. Those combinations were tested under 4 arrangements with an array of 6 vibrors. In both experiments, linear orientation aligned with the upper arm longitudinal axis were compared to circular orientation on the upper arm circumference. For both orientations, vibrors were placed either with 3cm space between the center of 2 vibrors or proportionally to the length or the circumference of the subject upper arm. Eleven heathy subjects underwent the 2 experiments and 7 amputees (humeral level) participated in the spatial discrimination task with the best arrangement found. RESULTS: Experiment 1 revealed that circular arrangements elicited better scores than the linear ones. Arrangements with vibrors spaced proportionally elicited better scores (up to 75% correct) than those with 3 cm spacing. Experiment 2, showed that the perceived intensity of the vibration increases with the intensity of the vibrors' activation, but also with their duration of activation. The 7 patients obtained high scores (up to 91.67% correct) with the circular proportional (CP) arrangement. DISCUSSION: These results highlight that discrete and short vibrations can be well discriminated by healthy subjects and people with an upper limb amputation. These new characteristics of vibrations have great potential for future sensory substitution application in closed-loop prosthetic control.

Comparing Gait Trials with Greedy Template Matching.

Gait assessment and quantification have received an increased interest in recent years. Embedded technologies and low-cost sensors can be used for the longitudinal follow-up of various populations (neurological diseases, elderly, etc.). However, the comparison of two gait trials remains a tricky question as standard gait features may prove to be insufficient in some cases. This article describes a new algorithm for comparing two gait trials recorded with inertial measurement units (IMUs). This algorithm uses a library of step templates extracted from one trial and attempts to detect similar steps in the second trial through a greedy template matching approach. The output of our method is a similarity index (SId) comprised between 0 and 1 that reflects the similarity between the patterns observed in both trials. Results on healthy and multiple sclerosis subjects show that this new comparison tool can be used for both inter-individual comparison and longitudinal follow-up.

Phase I trial of bortezomib daily dose: safety, pharmacokinetic profile, biological effects and early clinical evaluation in patients with advanced solid tumors.

Purpose This phase I study investigated bortezomib in solid tumors used as a daily subcutaneous regimen. Previous regimens showed only modest activity in solid tumors which was potentially related to sub-optimal tumor penetration. We aimed at exploring if daily low dose administration of bortezomib may allow a greater and tolerable pharmacokinetic exposure which might be required for antitumor activity in solid tumors. Patients and methods This 3 + 3 design, dose escalation, monocentric study aimed at defining the maximum tolerated dose of daily low dose schedule of bortezomib. Tolerability, pharmacokinetics, pharmacodynamics, antitumor activity, biomarkers for proteasome inhibition, pre- and post-treatment tumor biopsies were also evaluated. Results A total of eighteen patients were dosed in 3 bortezomib cohorts (0.5, 0.6 and 0.7 mg/m2), with 3, 11 and 4 patients respectively. Three patients experienced dose-limiting toxicities: Grade (G) 3 Sweet's syndrome (at 0.6 mg/m2), G3 asthenia and anorexia or ataxia (2 patients at 0.7 mg/m2). The most common study drug-related adverse events (all grades) were thrombocytopenia (72%), fatigue (56%), neuropathy (50%), anorexia (44%) and rash (39%). Dose 0.6 mg/m2 of bortezomib was considered as the recommended phase II dose. A significant tumor shrinkage (-36% according to WHO criteria) was observed in one patient with heavily pre-treated GIST, and 2 minor responses (-20%) were recorded in two patients with melanoma and mesothelioma. Conclusion This daily subcutaneous regimen of bortezomib showed a dose dependent plasma exposure, evidence of target inhibition and preliminary signs of clinical activity. However, cumulative neurological toxicity of this dose-dense daily regimen might preclude its further clinical development.

New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study.

BACKGROUND: Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria. METHODS: Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded. RESULTS: Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL). CONCLUSIONS: RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Template-Based Step Detection with Inertial Measurement Units.

This article presents a method for step detection from accelerometer and gyrometer signals recorded with Inertial Measurement Units (IMUs). The principle of our step detection algorithm is to recognize the start and end times of the steps in the signal thanks to a predefined library of templates. The algorithm is tested on a database of 1020 recordings, composed of healthy subjects and patients with various neurological or orthopedic troubles. Simulations on more than 40,000 steps show that the template-based method achieves remarkable results with a 98% recall and a 98% precision. The method adapts well to pathological subjects and can be used in a medical context for robust step estimation and gait characterization.

Neurological toxicities associated with immune-checkpoint inhibitors.

PURPOSE OF REVIEW: Immune-checkpoint inhibitors (ICIs) constitute a novel class of agents recently approved to treat a number of human malignancies. Due to their immunomodulatory mechanism of action, ICIs can generate a wide range of immune-related adverse events (irAEs) of which neurological toxicities are of special interest because of their potential severity. The objective of this review is to examine the recent literature describing neurological irAEs and discuss their optimal management. RECENT FINDINGS: As opposed to irAEs involving other organs, neurological complications of ICIs are uncommon. These complications encompass various toxicities of the central and peripheral nervous systems, including myositis, myasthenia gravis, demyelinating polyradiculoneuropathy, meningitis and encephalitis. Neurologic irAEs are often responsive to corticosteroids and other immune-modulating treatments (e.g. plasmapheresis, intravenous immunoglobulin), which have been used in patients presenting with severe neurologic irAEs or irAEs unresponsive to corticosteroids. Data from literature indicate that early treatment is critical for reducing the morbidity associated with neurologic irAEs. SUMMARY: ICI-associated irAEs constitute a new group of neurologic complications of systemic anticancer therapies. Although potentially severe, these rare neurologic toxicities are often responsive to immune-modulating therapies. Early recognition and treatment is crucial for timely improvement of functional outcome and requires a multidisciplinary approach.

Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.

Cognitive outcome after radiotherapy in brain tumor.

PURPOSE OF REVIEW: Survival of brain tumor patients has increased with improvements in cancer treatments. However, treatments like radiotherapy can be neurotoxic and thus new end-points in clinical trials, as well as in individual management, have appeared. This article reviews the cognitive outcomes after radiotherapy in brain tumor patients, focusing on radiation-induced impairments, and then discusses actual cognitive assessment limitations. RECENT FINDINGS: Although physiopathology of radiation-induced cognitive impairments remains elusive, a general course can be described as acute, early-delayed, and late-delayed effects corresponding to different processes. The last is of high interest because the related impairments are irreversible. In this context, a cognitive assessment should be performed as often as possible, but actual tools are unfortunately not developed. Nevertheless, with respect to neuro-oncologic specificities, new cognitive tools could be developed to overcome these limitations. SUMMARY: Improvements in neuropsychologic assessment for brain tumor patients are urgently needed. A dynamic vision of radiation-induced cognitive impairments appears inevitable and should lead to a change in actual considerations about neurotoxicity follow-up.

EpiBrainRad: an epidemiologic study of the neurotoxicity induced by radiotherapy in high grade glioma patients.

BACKGROUND: Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations. METHOD/DESIGN: The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement. DISCUSSION: With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors. TRIAL REGISTRATION: NCT02544178.