Damien Ricard

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

BackgroundRadiotherapy 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/DesignThe 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 3xa0years 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.DiscussionWith 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 RegistrationNCT02544178

A Non Linear Scoring Approach for Evaluating Balance: Classification of Elderly as Fallers and Non-Fallers.

Almost one third of population 65 years-old and older faces at least one fall per year. An accurate evaluation of the risk of fall through simple and easy-to-use measurements is an important issue in current clinic. A common way to evaluate balance in posturography is through the recording of the centre-of-pressure (CoP) displacement (statokinesigram) with force platforms. A variety of indices have been proposed to differentiate fallers from non fallers. However, no agreement has been reached whether these analyses alone can explain sufficiently the complex synergies of postural control. In this work, we study the statokinesigrams of 84 elderly subjects (80.3+− 6.4 years old), which had no impairment related to balance control. Each subject was recorded 25 seconds with eyes open and 25 seconds with eyes closed and information pertaining to the presence of problems of balance, such as fall, in the last six months, was collected. Five descriptors of the statokinesigrams were computed for each record, and a Ranking Forest algorithm was used to combine those features in order to evaluate each subject’s balance with a score. A classical train-test split approach was used to evaluate the performance of the method through ROC analysis. ROC analysis showed that the performance of each descriptor separately was close to a random classifier (AUC between 0.49 and 0.54). On the other hand, the score obtained by our method reached an AUC of 0.75 on the test set, consistent over multiple train-test split. This non linear multi-dimensional approach seems appropriate in evaluating complex postural control.

An Automated Recording Method in Clinical Consultation to Rate the Limp in Lower Limb Osteoarthritis.

For diagnosis and follow up, it is important to be able to quantify limp in an objective, and precise way adapted to daily clinical consultation. The purpose of this exploratory study was to determine if an inertial sensor-based method could provide simple features that correlate with the severity of lower limb osteoarthritis evaluated by the WOMAC index without the use of step detection in the signal processing. Forty-eight patients with lower limb osteoarthritis formed two severity groups separated by the median of the WOMAC index (G1, G2). Twelve asymptomatic age-matched control subjects formed the control group (G0). Subjects were asked to walk straight 10 meters forward and 10 meters back at self-selected walking speeds with inertial measurement units (IMU) (3-D accelerometers, 3-D gyroscopes and 3-D magnetometers) attached on the head, the lower back (L3-L4) and both feet. Sixty parameters corresponding to the mean and the root mean square (RMS) of the recorded signals on the various sensors (head, lower back and feet), in the various axes, in the various frames were computed. Parameters were defined as discriminating when they showed statistical differences between the three groups. In total, four parameters were found discriminating: mean and RMS of the norm of the acceleration in the horizontal plane for contralateral and ipsilateral foot in the doctor’s office frame. No discriminating parameter was found on the head or the lower back. No discriminating parameter was found in the sensor linked frames. This study showed that two IMUs placed on both feet and a step detection free signal processing method could be an objective and quantitative complement to the clinical examination of the physician in everyday practice. Our method provides new automatically computed parameters that could be used for the comprehension of lower limb osteoarthritis. It may not only be used in medical consultation to score patients but also to monitor the evolution of their clinical syndrome during and after rehabilitation. Finally, it paves the way for the quantification of gait in other fields such as neurology and for monitoring the gait at a patient’s home.

On the importance of local dynamics in statokinesigram: A multivariate approach for postural control evaluation in elderly

The fact that almost one third of population >65 years-old has at least one fall per year, makes the risk-of-fall assessment through easy-to-use measurements an important issue in current clinical practice. A common way to evaluate posture is through the recording of the center-of-pressure (CoP) displacement (statokinesigram) with force platforms. Most of the previous studies, assuming homogeneous statokinesigrams in quiet standing, used global parameters in order to characterize the statokinesigrams. However the latter analysis provides little information about local characteristics of statokinesigrams. In this study, we propose a multidimensional scoring approach which locally characterizes statokinesigrams on small time-periods, or blocks, while highlighting those which are more indicative to the general individual’s class (faller/non-faller). Moreover, this information can be used to provide a global score in order to evaluate the postural control and classify fallers/non-fallers. We evaluate our approach using the statokinesigram of 126 community-dwelling elderly (78.5 ± 7.7 years). Participants were recorded with eyes open and eyes closed (25 seconds each acquisition) and information about previous falls was collected. The performance of our findings are assessed using the receiver operating characteristics (ROC) analysis and the area under the curve (AUC). The results show that global scores provided by splitting statokinesigrams in smaller blocks and analyzing them locally, classify fallers/non-fallers more effectively (AUC = 0.77 ± 0.09 instead of AUC = 0.63 ± 0.12 for global analysis when splitting is not used). These promising results indicate that such methodology might provide supplementary information about the risk of fall of an individual and be of major usefulness in assessment of balance-related diseases such as Parkinson’s disease.

Neurologic Complications of Radiation Therapy

Radiation-induced nervous system toxicity remains a cause of morbidity in patients with cancer. Real advances in the design of safer radiation procedures have been counterbalanced by a wider use of combined radiotherapy-chemotherapy regimens, the development of radiosurgery, and the increasing number of long-term survivors. While classic radionecrosis have become less common, more subtle changes such as progressive cognitive dysfunction are increasingly reported after cranial radiotherapy (radiation-induced leukoencephalopathy) administered alone or in combination with chemotherapy. The most important and controversial complications of radiotherapy and combined treatments in the central nervous system and peripheral nervous system are reviewed here, including new diagnostic tools, practical management, and prevention.

Troubles cognitifs chimio-induits ou « chemobrain » : concept et état de l’art

Cognitive complaints are frequent in patients who received chemotherapy for a non-CNS cancer. These observations have been described as «xa0chemobrainxa0». However, studies results are contradictory concerning the implication of chemotherapy in the onset of cognitive defects. Moreover, other factors as mood, anxiety and fatigue are often associated in this population and could be confounding. This article present principal results of research in human experiencing chemobrain, concerning clinical presentation, neuropsychological examination, imaging techniques and treatment possibilities. Physiopathological hypothesis are presented. The implication of hormonotherapy is also discussed.

Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.

BACKGROUNDnDespite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities.nnnMETHODSnThis retrospective, multi-centrexa0study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8xa0weeks after termination of treatmentxa0and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded.nnnRESULTSnThirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (nxa0=xa018), PRES (nxa0=xa09), TIA (nxa0=xa06)xa0or haemorrhagic stroke (nxa0=xa01). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (nxa0=xa06), severe vascular toxicity recurred in two patients.nnnCONCLUSIONSnNeurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions.