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.

Tilt perception is different in the pitch and roll planes in human.

Neurophysiological tests probing the vestibulo-ocular, colic and spinal pathways are the gold standard to evaluate the vestibular system in clinics. In contrast, vestibular perception is rarely tested despite its potential usefulness in professional training and for the longitudinal follow-up of professionals dealing with complex man-machine interfaces, such as aircraft pilots. This is explored here using a helicopter flight simulator to probe the vestibular perception of pilots. The vestibular perception of nine professional helicopter pilots was tested using a full flight helicopter simulator. The cabin was tilted six times in roll and six times in pitch (-15°, -10°, -5°, 5°, 10° and 15°) while the pilots had no visual cue. The velocities of the outbound displacement of the cabin were kept below the threshold of the semicircular canal perception. After the completion of each movement, the pilots were asked to put the cabin back in the horizontal plane (still without visual cues). The order of the 12 trials was randomized with two additional control trials where the cabin stayed in the horizontal plane but rotated in yaw (-10° and +10°). Pilots were significantly more precise in roll (average error in roll: 1.15 ± 0.67°) than in pitch (average error in pitch: 2.89 ± 1.06°) (Wilcoxon signed-rank test: p < 0.01). However, we did not find a significant difference either between left and right roll tilts (p = 0.51) or between forward and backward pitch tilts (p = 0.59). Furthermore, we found that the accuracies were significantly biased with respect to the initial tilt. The greater the initial tilt was, the less precise the pilots were, although maintaining the direction of the tilt, meaning that the error can be expressed as a vestibular error gain in the ability to perceive the modification in the orientation. This significant result was found in both roll (Friedman test: p < 0.01) and pitch (p < 0.001). However, the pitch trend error was more prominent (gain = 0.77 vs gain = 0.93) than roll. This study is a first step in the determination of the perceptive-motor profile of pilots, which could be of major use for their training and their longitudinal follow-up. A similar protocol may also be useful in clinics to monitor the aging process of the otolith system with a simplified testing device.

Preventing falls: the use of machine learning for the prediction of future falls in individuals without history of fall.

Nowadays, it becomes of paramount societal importance to support many frail-prone groups in our society (elderly, patients with neurodegenerative diseases, etc.) to remain socially and physically active, maintain their quality of life, and avoid their loss of autonomy. Once older people enter the prefrail stage, they are already likely to experience falls whose consequences may accelerate the deterioration of their quality of life (injuries, fear of falling, reduction of physical activity). In that context, detecting frailty and high risk of fall at an early stage is the first line of defense against the detrimental consequences of fall. The second line of defense would be to develop original protocols to detect future fallers before any fall occur. This paper briefly summarizes the current advancements and perspectives that may arise from the combination of affordable and easy-to-use non-wearable systems (force platforms, 3D tracking motion systems), wearable systems (accelerometers, gyroscopes, inertial measurement units-IMUs) with appropriate machine learning analytics, as well as the efforts to address these challenges.

A review of center of pressure (COP) variables to quantify standing balance in elderly people: Algorithms and open-access code.

Postural control is often quantified by recording the trajectory of the center of pressure (COP)-also called stabilogram-during human quiet standing. This quantification has many important applications, such as the early detection of balance degradation to prevent falls, a crucial task whose relevance increases with the aging of the population. Due to the complexity of the quantification process, the analyses of sway patterns have been performed empirically using a number of variables, such as ellipse confidence area or mean velocity. This study reviews and compares a wide range of state-of-the-art variables that are used to assess the risk of fall in elderly from a stabilogram. When appropriate, we discuss the hypothesis and mathematical assumptions that underlie these variables, and we propose a reproducible method to compute each of them. Additionally, we provide a statistical description of their behavior on two datasets recorded in two elderly populations and with different protocols, to hint at typical values of these variables. First, the balance of 133 elderly individuals, including 32 fallers, was measured on a relatively inexpensive, portable force platform (Wii Balance Board, Nintendo) with a 25-s open-eyes protocol. Second, the recordings of 76 elderly individuals, from an open access database commonly used to test static balance analyses, were used to compute the values of the variables on 60-s eyes-open recordings with a research laboratory standard force platform.

An opinion paper on the maintenance of robustness: Towards a multimodal and intergenerational approach using digital twins.

The increasing number of frail elderly people in our aging society is becoming problematic: about 11% of community-dwelling older persons are frail and another 42% are pre-frail. Consequently, a major challenge in the coming years will be to test people over the age of 60 years to detect pre-frailty at the earliest stage and to return them to robustness using the targeted interventions that are becoming increasingly available. This challenge requires individual longitudinal monitoring (ILM) or follow-up of community-dwelling older persons using quantitative approaches. This paper briefly describes an effort to tackle this challenge. Extending the detection of the pre-frail stages to other population groups is also suggested. Appropriate algorithms have been used to begin the tracing of faint physiological signals in order to detect transitions from robustness to pre-frailty states and from pre-frailty to frailty states. It is hoped that these studies will allow older adults to receive preventive treatment at the correct institutions and by the appropriate professionals as early as possible, which will prevent loss of autonomy. Altogether, ILM is conceived as an emerging property of databases ("digital twins") and not the reverse. Furthermore, ILM should facilitate a coordinated set of actions by the caregivers, which is a complex challenge in itself. This approach should be gradually extended to all ages, because frailty has no age, as is testified by overwork, burnout, and post-traumatic syndrome.

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.

Balance Impairment in Radiation Induced Leukoencephalopathy Patients Is Coupled With Altered Visual Attention in Natural Tasks.

Background: Recent studies have shown that alterations in executive function and attention lead to balance control disturbances. One way of exploring the allocation of attention is to record eye movements. Most experimental data come from a free viewing of static scenes but additional information can be leveraged by recording eye movements during natural tasks. Here, we aimed to provide evidence of a correlation between impaired visual alteration in natural tasks and postural control in patients suffering from Radiation-Induced Leukoencephalopathy (RIL). Methods: The study subjects were nine healthy controls and 10 patients who were diagnosed with RIL at an early stage, with isolated dysexecutive syndrome without clinically detectable gait or posture impairment. We performed a balance evaluation and eye movement recording during an ecological task (reading a recipe while cooking). We calculated a postural score and oculomotor parameters already proposed in the literature. We performed a variable selection using an out-of-bag random permutation and a random forest regression algorithm to find: (i) if visual parameters can predict postural deficit and, (ii) which are the most important of them in this prediction. Results were validated using the leave-one-out cross-validation procedure. Results: Postural scores indeed were found significantly lower in patients with RIL than in healthy controls. Visual parameters were found able to predict the postural score of RIL patients with normalized root mean square error (RMSE) of 0.16. The present analysis showed that horizontal and vertical eye movements, as well as the average duration of the saccades and fixations influenced significantly the prediction of the postural score in RIL patients. While two patients with very low MATTIS-Attention sub score showed the lowest postural scores, no statistically significant relationship was found between the two outcomes. Conclusion: These results highlight the significant relationship between the severity of balance deficits and the visual characteristics in RIL patients. It seems that increased balance impairment is coupled with a reduced focusing capacity in ecological tasks. Balance and eye movement recordings during a natural task could be a useful aspect of multidimensional scoring of the dysexecutive syndrome.

Inertial Sensors to Assess Gait Quality in Patients with Neurological Disorders: A Systematic Review of Technical and Analytical Challenges.

Gait disorders are major causes of falls in patients with neurological diseases. Understanding these disorders allows prevention and better insights into underlying diseases. InertiaLocoGraphy (ILG) -the quantification of gait by using inertial measurement units (IMUs) -shows great potential to address this public health challenge, but protocols vary widely and normative values of gait parameters are still unavailable. This systematic review critically compares ILG protocols, questions features extracted from inertial signals and proposes a semeiological analysis of clinimetric characteristics for use in neurological clinical routine. For this systematic review, PubMed, Cochrane and EMBASE were searched for articles assessing gait quality by using IMUs that were published from January 1, 2014 to August 31, 2016. ILG was used to assess gait in a wide range of neurological disorders - including Parkinson disease, mild cognitive impairment, Alzheimer disease, cerebral palsy, and cerebellar atrophy - as well as in the faller or frail older population and in people presenting rheumatological pathologies. However, results have not yet been driving changes in clinical practice. One reason could be that studies mainly aimed at comparing pathological gait to healthy gait, but there is stronger need for semiological descriptions of gait perturbation, severity or prognostic assessment. Furthermore, protocols used to assess gait using IMUs are too many. Likely, outcomes are highly heterogeneous and difficult to compare across large panels of studies. Therefore, homogenization is needed to foster the use of ILG to assess gait quality in neurological routine practice. The pros and cons of each protocol are emphasized so that a compromise can be reached. As well, analysis of seven complementary clinical criteria (springiness, sturdiness, smoothness, steadiness, stability, symmetry, synchronization) is advocated.

Observational Study of 180° Turning Strategies Using Inertial Measurement Units and Fall Risk in Poststroke Hemiparetic Patients.

OBJECTIVE: We analyzed spontaneous 180° turning strategies in poststroke hemiparetic patients by using inertial measurement units (IMUs) and the association of turning strategies with risk of falls. METHODS: We included right paretic (RP) and left paretic (LP) post-stroke patients, and healthy controls (HCs) from a physical and rehabilitation department in France between July 2015 and October 2015. All subjects were right-handed and right-footed for mobilization tasks. Participants were instructed to turn 180° in a self-selected direction after a 10-m walk while wearing three IMUs on their trunk and both feet. We defined three turning patterns based on the number of external steps (pattern I = 1; II = 2-4 steps; and III ≥ 5) and four turning strategies based on the side chosen to turn (healthy or paretic) and the stance limb used during the first step of the turn (healthy or paretic). Falls in the 6 months after measurement were investigated. RESULTS: We included 17 RP [mean (SD) age 57.5 (9.5) years (range 43-73)], 20 LP patients [mean age 60.7 (8.8) years (range 43-63)], and 15 HCs [mean age 56.7 (16.1) years (range 36-83)]. The LP and RP groups behaved similarly in turning patterns, but 90% of LP patients turned spontaneously to the paretic side versus 59% of RP patients. This difference increased with turning strategies: 85% of LP versus 29% of RP patients used strategy 4 (paretic turn side with paretic limb). Patients using strategy 4 had the highest rate of falls. CONCLUSION: We propose to consider spontaneous turning strategies as new indicators to evaluate the risk of fall after stroke. IMU could be routinely used to identify this risk and guide balance rehabilitation programs.

OB3D, a new set of 3D objects available for research: a web-based study.

Studying object recognition is central to fundamental and clinical research on cognitive functions but suffers from the limitations of the available sets that cannot always be modified and adapted to meet the specific goals of each study. We here present a new set of 3D scans of real objects available on-line as ASCII files, OB3D. These files are lists of dots, each defined by a triplet of spatial coordinates and their normal that allow simple and highly versatile transformations and adaptations. We performed a web-based experiment to evaluate the minimal number of dots required for the denomination and categorization of these objects, thus providing a reference threshold. We further analyze several other variables derived from this data set, such as the correlations with object complexity. This new stimulus set, which was found to activate the Lower Occipital Complex (LOC) in another study, may be of interest for studies of cognitive functions in healthy participants and patients with cognitive impairments, including visual perception, language, memory, etc.

Repetition blindness for natural images of objects with viewpoint changes.

When stimuli are repeated in a rapid serial visual presentation (RSVP), observers sometimes fail to report the second occurrence of a target. This phenomenon is referred to as "repetition blindness" (RB). We report an RSVP experiment with photographs in which we manipulated object viewpoints between the first and second occurrences of a target (0°, 45°, or 90° changes), and spatial frequency (SF) content. Natural images were spatially filtered to produce low, medium, or high SF stimuli. RB was observed for all filtering conditions. Surprisingly, for full-spectrum (FS) images, RB increased significantly as the viewpoint reached 90°. For filtered images, a similar pattern of results was found for all conditions except for medium SF stimuli. These findings suggest that object recognition in RSVP are subtended by viewpoint-specific representations for all spatial frequencies except medium ones.