Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Early post-stroke period: A privileged time for sensory re-weighting?

International audienceBACKGROUND: Shortly after stroke, patients exhibit excessive sensitivity to visual, proprioceptive and vestibular perturbations regarding balance control. OBJECTIVE: To evaluate the stability of this perceptual behaviour after stroke and test the relationships between sensory sensitivity and balance. METHODS: Thirty subjects following a hemispheric stroke (mean age 54.7 (standard deviation (SD) 10.6 years), 21 men, right hemisphere lesion = 13) and 30 control subjects (mean age 52.0 (SD 12.0), 14 men). Sensitivity to sensory perturbations was evaluated using the displacement of the centre of pressure during tendon vibration (proprioception score), optokinetic (visual score) and galvanic perturbations (vestibular score) while standing on a force-platform a mean of 2 months after stroke, and 1 month later. Balance and independence were evaluated using the Berg Balance Scale (BBS), Timed Up and Go test (TUG) and Barthel Index (BI). RESULTS: Global sensitivity to perturbations decreased (p = 0.001). Patients remained more sensitive to visual perturbation than did controls (p = 0.033). The Vestibular Score was correlated with BBS (Rs = -0.576, p = 0.006), TUG (Rs = 0.408, p = 0.045), BI (Rs = -0.481, p = 0.016); the Visual Score was correlated with BBS (Rs = -0.500, p = 0.019), TUG (Rs = 0.401, p = 0.049). CONCLUSION: The initial months following stroke appear to be a period of individual perceptual motor adaptation. Sensory re-weighting is likely to be a major component of that process

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

ObjectiveWe 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.MethodsWe 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.ResultsWe 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.ConclusionWe 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

Standing postural reaction to visual and proprioceptive stimulation in chronic acquired demyelinating polyneuropathy

Objective: To investigate the weight of visual and proprioceptive inputs, measured indirectly in standing position control, in patients with chronic acquired demyelinating polyneuropathy (CADP). Design: Prospective case study. Subjects: Twenty-five patients with CADP and 25 healthy controls. Methods: Posture was recorded on a double force platform. Stimulations were optokinetic (60°/s) for visual input and vibration (50 Hz) for proprioceptive input. Visual stimulation involved 4 tests (upward, downward, rightward and leftward) and proprioceptive stimulation 2 tests (triceps surae and tibialis anterior). A composite score, previously published and slightly modified, was used for the recorded postural signals from the different stimulations. Results: Despite their sensitivity deficits, patients with CADP were more sensitive to proprioceptive stimuli than were healthy controls (mean composite score 13.9 ((standard deviation; SD) 4.8) vs 18.4 (SD 4.8), p = 0.002). As expected, they were also more sensitive to visual stimuli (mean composite score 10.5 (SD 8.7) vs 22.9 (SD 7.5), p< 0.0001). Conclusion: These results encourage balance rehabilitation of patients with CADP, aimed at promoting the use of proprioceptive information, thereby reducing too-early development of visual compensation while proprioception is still available

Stocktaking on the development of posturography for clinical use

This report identifies fundamental problems to be addressed in order to build relevant clinical tests of human balance while standing. The stated purpose of these tests is identification of lesion site and/or definition of functional balance deficits in a specific patient. During a recent consensus meeting (ESCEBD), 60 researchers and experienced clinical users of posturography (14 European countries, 9 different disciplines) inventoried and critically analyzed the various methodologies of posturography currently used for clinical evaluation. To complement posturography, alternative methods of assessment of balance control were considered. The indications for the clinical use of posturography were defined as well as recommendations regarding measurement parameters, type of perturbations and signal analysis techniques to improve assessment of balance control. Consensus was reached that a force platform cannot be considered as a technique which is sufficient on its own to perform a clinically relevant test for the assessment of neuro-otological and musculo-skeletal conditions, evaluation of compensation or treatment (rehabilitation) or prediction of falls. It should be supported by complementary methods, such as segment motion analysis, body-fixed 2D or 3D accelerometer-gyroscope or electromyography. At present, no generally applicable posturography test is available with reasonable sensitivity and specificity for the diagnosis of balance disorders. Perturbation techniques are most likely needed to enhance the diagnostic yield of posturography

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

<div><p>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 <i>blocks</i>, 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.</p></div

Rehabilitation of balance after stroke with multisensorial training: a single-blind randomized controlled study.

International audienceOBJECTIVE: To compare 2 rehabilitation strategies to improve balance after stroke: (1) a multisensorial approach based on higher intensity of balance tasks and exercise during visual deprivation and (2) a conventional neurodevelopmentaltheory-based treatment (NDT) that used a general approach for sensorimotor rehabilitation. METHODS: This prospective, multicenter, randomized, parallel-group study measured outcomes with blinded assessors. Sixty-eight patients able to walk without human assistance were entered from 3 to 15 months (mean, 7 months) after a first hemispheric stroke. They received 20 sessions in 4 weeks of NDT or multisensorial rehabilitation. On day 0, day 30, and day 90, assessment included the Berg Balance Scale (BBS), posturography, gait (velocity, double stance phase, climbing 10 steps, amount of walking per day), the Functional Independence Measure, and the Nottingham Health Profile. RESULTS: All subjects improved significantly in balance and walking parameters. Regarding the main dependent variable (BBS on day 30), no difference between groups was found. Analysis of secondary outcomes suggested small differences in favor of the experimental group, but the differences are not likely to be clinically relevant. CONCLUSION: No evidence was found for the superiority of a multisensorial rehabilitation program in ambulatory patients with impairments beyond the time of inpatient therapy. Additional studies are recommended

Representation of the analysis of four statokinesigrams that have not easily distinguishable statokinesigrams(two fallers, two non-fallers) deduced from the CoP antero-posterior and medio-lateral using block-length of 1 second.

<p>It can be observed that although all the examples include parts that are strongly classified as possible UBs, these parts are more frequent in fallers than in non-fallers.</p

Probability density for the two-component mixture distribution (95%) and three-second-blocks of A) Non-fallers and B)Fallers, illustrated in the normalized 3-dimensional space.

<p>The two normal components overlap, but their centers are distinct. Many faller-derived periods are closer to the QBs component and conversely, many non-faller derived blocks are closer to the UBs centre.</p