Kinect-based assessment of proximal arm non-use after a stroke.

BACKGROUND: After a stroke, during seated reaching with their paretic upper limb, many patients spontaneously replace the use of their arm by trunk compensation movements, even though they are able to use their arm when forced to do so. We previously quantified this proximal arm non-use (PANU) with a motion capture system (Zebris, CMS20s). The aim of this study was to validate a low-cost Microsoft Kinect-based system against the CMS20s reference system to diagnose PANU. METHODS: In 19 hemiparetic stroke individuals, the PANU score, reach length, trunk length, and proximal arm use (PAU) were measured during seated reaching simultaneously by the Kinect (v2) and the CMS20s over two testing sessions separated by two hours. RESULTS: Intraclass correlation coefficients (ICC) and linear regression analysis showed that the PANU score (ICC = 0.96, r2 = 0.92), reach length (ICC = 0.81, r2 = 0.68), trunk length (ICC = 0.97, r2 = 0.94) and PAU (ICC = 0.97, r2 = 0.94) measured using the Kinect were strongly related to those measured using the CMS20s. The PANU scores showed good test-retest reliability for both the Kinect (ICC = 0.76) and CMS20s (ICC = 0.72). Bland and Altman plots showed slightly reduced PANU scores in the re-test session for both systems (Kinect: - 4.25 ± 6.76; CMS20s: - 4.71 ± 7.88), which suggests a practice effect. CONCLUSION: We showed that the Kinect could accurately and reliably assess PANU, reach length, trunk length and PAU during seated reaching in post stroke individuals. We conclude that the Kinect can offer a low-cost and widely available solution to clinically assess PANU for individualised rehabilitation and to monitor the progress of paretic arm recovery. TRIAL REGISTRATION: The study was approved by The Ethics Committee of Montpellier, France (N°ID-RCB: 2014-A00395-42) and registered in Clinical Trial (N° NCT02326688, Registered on 15 December 2014, https://clinicaltrials.gov/ct2/show/results/NCT02326688 ).

Kinematics in the brain: unmasking motor control strategies?

In rhythmical movement performance, our brain has to sustain movement while correcting for biological noise-induced variability. Here, we explored the functional anatomy of brain networks during voluntary rhythmical elbow flexion/extension using kinematic movement regressors in fMRI analysis to verify the interest of method to address motor control in a neurological population. We found the expected systematic activation of the primary sensorimotor network that is suggested to generate the rhythmical movement. By adding the kinematic regressors to the model, we demonstrated the potential involvement of cerebellar-frontal circuits as a function of the irregularity of the variability of the movement and the primary sensory cortex in relation to the trajectory length during task execution. We suggested that different functional brain networks were related to two different aspects of rhythmical performance: rhythmicity and error control. Concerning the latter, the partitioning between more automatic control involving cerebellar-frontal circuits versus less automatic control involving the sensory cortex seemed thereby crucial for optimal performance. Our results highlight the potential of using co-registered fine-grained kinematics and fMRI measures to interpret functional MRI activations and to potentially unmask the organisation of neural correlates during motor control.

Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR® approach.

Scaling up and replication of successful innovative integrated care models for chronic diseases is one of the targets of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). MACVIA-LR® (MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon) is a Reference Site of the EIP on AHA. The main objective of MACVIA-LR® is to develop innovative solutions in order to (1) improve the care of patients affected by chronic diseases, (2) reduce avoidable hospitalization and (3) scale up the innovation to regions of Europe. The MACVIA-LR® project also aims to assess all possible aspects of medicine-including non-pharmacologic approaches-in order to maintain health and prevent chronic diseases. These approaches include hydrotherapy and balneotherapy which can be of great importance if health promotion strategies are considered. Balneotherapy at Balaruc-les-Bains focusses on musculoskeletal diseases and chronic venous insufficiency of the lower limbs. Each year, over 46,000 people attend an 18-day course related to a new falls prevention initiative combining balneotherapy and education. On arrival, each person receives a flyer providing information on the risk of fall and, depending on this risk, a course is proposed combining education and physical activity. A pilot study assesses the impact of the course 6 and 12 months later. This health promotion strategy for active and healthy ageing follows the FEMTEC (World Federation of Hydrotherapy and Climatotherapy) concept.

Aging effects on electrical and hemodynamic responses in the sensorimotor network during unilateral proximal upper limb functional tasks.

Healthy aging leads to poorer performance in upper limb (UL) daily living movements. Understanding the neural correlates linked with UL functional movements may help to better understand how healthy aging affects motor control. Two non-invasive neuroimaging methods allow for monitoring the movement-related brain activity: functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), respectively based on the hemodynamic response and electrical activity of brain regions. Coupled, they provide a better spatiotemporal mapping. The aim of this study was to evaluate the effect of healthy aging on the bilateral sensorimotor (SM1) activation patterns of functional proximal UL movements. Twenty-one young and 21 old healthy participants realized two unilateral proximal UL movements during: i) a paced reaching target task and ii) a circular steering task to capture the speed-accuracy trade-off. Combined fNIRS-EEG system was synchronised with movement capture system to record SM1 activation while moving. The circular steering task performance was significantly lower for the older group. The rate of increase in hemodynamic response was longer in the older group with no difference on the amplitude of fNIRS signal for the two tasks. The EEG results showed aging related reduction of the alpha-beta rhythms synchronisation but no desynchronisation modification. In conclusion, this study uncovers the age-related changes in brain electrical and hemodynamic response patterns in the bilateral sensorimotor network during two functional proximal UL movements using two complementary neuroimaging methods. This opens up the possibility to utilise combined fNIRS-EEG for monitoring the movement-related neuroplasticity in clinical practice.

What can be expected from tendon transfers in the upper limb in central nervous system disorders?

In addition to motor deficits, central nervous system disorders combine major alterations in the motor pattern with spasticity and over time, contractures. Their varied clinical presentation makes their assessment and the therapeutic strategy more complex. For these reasons, tendon transfers in this population will have more limited indications and above all, will have to be integrated into a complex surgical program combining other procedures such as tendon lengthening, selective neurotomies and joint stabilization. The surgical strategy is far from being obvious. When faced with clinical presentations having very different objectives-functional or comfort only-it is difficult at first sight to build a standardized surgical program. We therefore propose a method to evaluate these patients, thanks to a score (INOM) that integrates prognostic factors and parameters to be corrected surgically. Three components guide this program: a prognostic factor (proximal motor control of the shoulder and elbow), correction of abnormal limb postures and restoration of active elbow, wrist and finger extension. The surgical strategy can be constructed from the INOM score which establishes the priorities for care. Nerve blocks and botulinum toxin injections are essential tools for this analysis. They help distinguish between spasticity and contracture, and can unmask certain antagonistic muscles. A tendon transfer in this population will be just as effective by the function it restores as by the action it suppresses in a malpositioned limb. For each joint, we describe the indications for tendon transfers and their relative role among the techniques with which they must be combined.

Assessment of the upper limb of the tetraplegic patient.

The aim of our study is to describe the assessment of the upper limb in tetraplegic patients to follow his (her) neurological progression and to define the medical or surgical treatment program. We selected upper limb assessment tools and scales for tetraplegic patients described in the medical literature through a PubMed search over the last four decades. For each method, we present the implementation rules and its metrological properties, including its validity in French. We selected five clinical scales for functional evaluation of grasping, as well as four scales for evaluating the overall function of these patients. Finally, we identified three complementary precision assessment tools. The AIS (ASIA Impairment Scale) classification describes the level and the severity of the spinal cord lesion. The Giens classification is more practical for describing the upper limb in middle and low tetraplegia. Impairments can be assessed with most common generic scales and nonspecific measurement devices: range of motion, strength, sensory loss, spasticity, joint pain. Measurement of pinch and grip strength is widely used and easy to perform. The Capabilities of Upper Extremity (CUE) and the Jebsen Taylor Test are the best validated and usable scales. At a general functional level, the Spinal Cord Independence Measure (SCIM) is the most relevant scale in these patients. Motor nerve blocks, electromyography, movement analysis and echography are promising additional methods. Assessment of the upper limb of tetraplegic patients relies both on generic and specific assessment tools and scales.

Self-catheterization acquisition after hand reanimation protocols in C5-C7 tetraplegic patients.

STUDY DESIGN: Case series from a prospectively acquired database and phone survey. OBJECTIVES: To assess the efficacy of upper limb reanimation (ULR) protocols on acquisition of intermittent self-catheterization (ISC) in C5-C7 ASIA tetraplegic patients. SETTING: University Hospital, Paris, France. METHODS: A prospectively acquired database of 152 tetraplegic patients followed in ULR consultation between 1997 and 2008 in a rehabilitation unit was studied. A total of 20 patients met the inclusion criteria, which mainly were traumatic C5-C7 tetraplegic adult patients who were unable to perform ISC, and who benefited from ULR with the objectives of improving hand abilities and of ISC acquisition, through urethral orifice for males or via a continent urinary stoma for females. The main outcome measure was ISC acquisition (ISC+) proportion. Population characteristics and secondary outcome measures: ISC+/ISC- patients were compared regarding epidemiological and surgical data, key-grip strength, patient global improvement score, activities of daily living and quality of life (PGI-I, Wuolle questionnaire, verbal rating scale). RESULTS: ISC+ was 75%. It depended on key-grip strength (P<0.05) and led to a statistically significant improvement of urinary status compared with ISC- patients (P<0.01). ULR improved patients' abilities and QoL in both ISC+ and ISC- patients. CONCLUSION: ULR protocols allow ISC in most C5-C7 tetraplegic patients. Multidisciplinary care with surgeons and PRM physicians improves patients' vital and functional prognosis by changing their urological-management method.

Relation between corset use and lung function postural variation in spinal cord injury.

Corsets are widely used to improve trunk stability in patients with spinal cord injury (SCI) and can improve respiratory function. The aim of the present study was to identify predictors of respiratory benefits from wearing a corset in SCI patients. In a prospective observational study, respiratory function was tested in the supine and upright seated position with and without a corset in 36 SCI patients who regularly used a corset. SCI patients who no longer used a corset were matched to users on sex, injury level and severity. Vital capacity (VC) did not differ between users and nonusers in the supine position. In users, contrary to nonusers, VC increased significantly in the supine position compared to the seated position (increase of 0.43+/-0.39 versus -0.05+/-0.32 L in nonusers; p<0.0001). Corset use was associated with a significant VC increase in the upright position (2.13+/-0.71 L without versus 2.41+/-0.69 L with the corset; p<0.001). The VC increase with the corset in the upright position correlated significantly with the VC increase induced by being supine, compared to sitting without the corset. The VC increase induced in SCI patients by lying supine may predict the effects of wearing a corset. The long-term effects of corset use should be evaluated.

Upper limb surgery for tetraplegia: assessment of a 10-point strategy.

PURPOSE: Palliative motor surgery of the tetraplegic upper limb is well-defined, with relatively precise indications that however vary somewhat from team to team. Our personal indications originated mainly from Zancolli, and were applied by the same surgeon in two independent rehabilitation centers. The goals of this study were to assess the application of these indications with time. METHODS: Our retrospective study included three parts: summarization of our initial indications into a 10-point reference strategy; gathering the medical records related to all of the tetraplegic upper limb operations from 1989 to 2006, except for those related to complications and/or salvage procedures. For each patient, collected data corresponded to the 10 strategic points (SP); comparison of the collected data with the reference strategy, upper limb by upper limb, point by point, in order to identify and document any deviations. RESULTS: We assessed the use of the reference strategy in 272 consecutive operations (139 upper limbs, 96 patients). Overall nonconformity rate with the use of the 10-point strategy was 27% (38/139). Except for one very atypical case, all of the exceptions from the reference strategy were due to specific anatomical or physiological conditions. CONCLUSIONS: Our reference strategy has remained noticeably stable over time. However, three important evolutionary modifications occurred: systematic choice of biceps instead of deltoid to restore elbow extension; addition of the split distal flexor pollicis longus tenodesis procedure; and removal of extensor carpi radialis brevis from the list of potential flexor pollicis longus motors. Two issues, dealing with the systematic use of lassos and with brachio radialis to extensor digitorum communis transfer, are likely to be revisited in the future.

Results and complications of superficialis-to-profundus tendon transfer in brain-damaged patients, a series of 26 patients.

INTRODUCTION: In hemiplegic patients with a spastic clenched fist deformity, one of the goals of surgery is to address the hygiene, nursing and appearance problems. Transfer of the flexor digitorum superficialis (FDS) to the flexor digitorum profundus (FDP), initially described by Braun and colleagues, opens the non-functional hand in these patients. The primary objective of our study was to confirm the effectiveness of this technique for correcting these deformities. The secondary objectives were to demonstrate potential functional gains and to identify potential complications. MATERIAL AND METHODS: A Braun procedure was performed in 26 patients (9 women, 17 men, ranging in age from 36 to 79 years). The overall appearance of the hand was graded using the Keenan classification system. Complications related to the surgery were documented. The hand's function was evaluated with the House score. RESULTS: The average follow-up was 47 months. Preoperatively, all patients had a class V hand: severe clenched-fist deformity with zero pulp-to-palm distance. Postoperatively, 10 patients had a type I hand (open hand, with less than 20° spontaneous extension deficit of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints) and 12 patients had a type II hand (20° to 40° spontaneous extension deficit of the MCP and PIP joints). The mean House score for all patients went from 0 to 0.88, and seven patients had functional improvements. Four patients had a forearm supination posture, 10 had intrinsic deformity with spontaneous MCP flexion and 6 had a swan-neck deformity. CONCLUSION: Superficialis-to-profundus tendon transfer (STP) provides satisfactory outcomes in terms of hand opening, with some patients also experiencing improved hand function. However, the complications cannot be ignored. LEVEL OF EVIDENCE: IV-retrospective or historical series.

Proximal arm non-use when reaching after a stroke.

After a stroke, many people "cannot and do not" use their paretic upper limb. With recovery, some people "can but do not" use their paretic upper limb and this non-use should be counteracted with specific rehabilitation. The aim of the study was to quantify one aspect of the non-use: proximal arm non-use when reaching within one's arm length in 45 post-stroke and 45 age matched controls. Arm use refers to the contribution of the shoulder and elbow motion to the hand movement towards the target. Proximal arm non-use is calculated as the ratio of the difference between spontaneous arm use and maximal arm use. We found that proximal arm non-use has very good test-retest reliability, does not depend on time since stroke, increases with impairment (Fugl-Meyer) and loss of function (Box & Block), and most importantly, that 61% of patients with lower impairment (Fugl-Meyer >28/42) exhibit proximal arm non-use. We conclude that quantifying proximal arm non-use in post-stroke individuals provides novel information that complements routine clinical measures. It is likely that proximal arm non-use quantifies one aspect of the motor reserve that therapists can target in patient specific rehabilitation programs.

Health related quality of life in people with hereditary neuromuscular diseases: an investigation of test-retest agreement with comparison between two generic questionnaires, the Nottingham health profile and the short form-36 items.

The present work attempts to define reproducibility, test-retest and internal consistencies of two standardised tools that measure health related quality of life (HRQoL), specifically as they apply to hereditary neuromuscular disease (HNMD): the Nottingham health profile (NHP) and the medical outcome study 36-item short-form questionnaire (MOS SF-36). A cross sectional survey of 108 hereditary neuromuscular disease patients completed the questionnaires consecutively in the course of multidisciplinary consultations in Reims between April 2002 and February 2005. The results of the study confirm the acceptability of using generic questionnaires such as the Nottingham health profile and the SF-36, and show good reliability for these instruments. For both instruments, reproducibility (test-retest) appears excellent for the physical dimensions explored, and satisfactory for the mental dimensions. There is nonetheless a need for health related quality of life measures validated for neuromuscular disease patients. Health related quality-of-life (HRQoL) measures provide information on how patients assess their health and the care provision they are offered.

How to extend the elbow with a weak or paralyzed triceps: control of arm kinematics for aiming in C6-C7 quadriplegic patients.

This study aims to investigate how quadriplegic patients with a C6-C7 spinal lesion coordinate their upper limb to extend the elbow despite the paralysis or weakness of the triceps brachii, and what is the effect of a surgical musculotendinous transfer. For this purpose, aiming movements in a wide workspace were recorded in seven healthy subjects and in patients with incomplete (five cases) or complete (eight cases) triceps paralysis and after musculotendinous transfer (eight cases). We used four electromagnetic field sensors to quantify hand trajectory and to compute the angles describing the rotations at the scapula, glenohumeral joint, elbow and wrist (10 degrees of freedom). Extent and smoothness of the hand trajectories and hand velocity profiles were surprisingly similar between healthy subjects and quadriplegic patients. The reduction of elbow extension observed in patients was compensated by rotations distributed across several degrees of freedom including the scapula. Principal components analysis showed that the joint rotations could be summarized by an additive combination of two synergies, respectively orientating and stretching out the limb, which explained similar amounts of variance in healthy subjects and in patients. The participations of degrees of freedom in the synergies were roughly similar in the different groups of subjects, the main difference concerning scapular medial-lateral rotation, which seems to be critical in patients with a complete triceps paralysis. This demonstrates that elbow extension in quadriplegic patients is due to anticipated mechanical interaction coupling between upper limb segments. We propose that the persisting (incomplete paralysis) or restored (musculotendinous transfer) elbow extensor strength may act by stabilizing the elbow. This counterintuitive preservation of limb kinematics for horizontal aiming movements in quadriplegic patients despite the drastic changes in muscle action provoked by paralysis and/or by surgery strongly suggests that the motor system does not primarily control forces but the morphological aspects of movement, via joint rotation synergies.

[Transforaminal epidural steroid injection and paraplegia: case report and bibliographic review]. / Paraplégie à la suite d'une infiltration foraminale lombaire: revue de la littérature à partir d'un cas.

OBJECTIVES: We report a patient in whom paraplegia developed following transforaminal epidural injection of a corticosteroid and discuss the physiopathology of this complication, based on a literature survey. CASE REPORT: A 40-year-old man presented with low-back pain and symptoms of L4 radiculopathy due to degenerative disc herniation resistant to conventional medical treatment. Computed tomography revealed posterolateral L4-L5 disc protrusion. A dosage of 125 mg of hydrocortisone was given by epidural transforaminal L4-L5 left injection under radioscopy guidance. Within minutes following the injection, intense pain developed in both legs, with T12 complete paraplegia. Emergency magnetic resonance imaging (MRI) 2 hours later did not reveal spinal cord abnormalities. The patient underwent immediate surgery consisting of excising the protruding disc and extensive L3-L5 laminectomy. MRI performed 3 months later did not reveal medullar abnormalities. Six months later, the patient continued to show slow neurologic improvement, permitting him to walk with crutches and to stop intermittent self-catheterisation. DISCUSSION: The occurrence of paraplegia following epidural transforaminal injection of corticosteroids is a rare complication. To our knowledge, only 5 similar cases have been described. Most of the authors proposed that the mechanism of this complication is ischemia of the terminal cone due to accidental suppression of medullary blood supply. Direct lesion of a medullar artery, arterial spasm, or corticosteroid-induced occlusion due to undetected intra-arterial injection could lead to this medullar infarction. Anatomical variations of the path followed by the Adamkievicz artery strongly support this hypothesis.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

[Constituted adult equine from the ankle: surgical treatment by Ilizarov external fixator]. / Pieds équins constitués de l'adulte: correction par fixateur externe d'Ilizarov.

INTRODUCTION: Ilizarov's external fixator indications are classically used in children to lengthen the lower limbs. This technique is used for adults to gradually correct articular limitations, especially in the knee, ankle and foot. METHOD AND RESULTS: We report a case of a 53-year-old patient with distal microangiopathy of the lower limbs leading to amputation of the toes and a bilateral, direct, irreducible, isolated equine feature? from the back foot to 0/50/60 degrees? on retraction of the Achilles tendon. The aim of patient management was to regain walking ability. Because of vascular and cutaneous fragility, the classical surgical treatment was contra-indicated. Progressive reduction by Ilizarov's external fixator was tried. Dorsal inflection was obtained by twice-daily screwing until a radiological angle of 90 degrees was obtained between the tibia and talus. At ten weeks post-surgery, the dorsal voluntary inflection ankle amplitude was symmetrical to 0/10/60 degrees. The patient walked with orthopaedic shoes compensating for the few degrees of residual equine. DISCUSSION: Correction of adult equine without osseous deformation by Ilizarov's external fixator should be considered when conventional surgery is contra-indicated.

Brain computer interfaces for neurorehabilitation ­ its current status as a rehabilitation strategy post-stroke.

The idea of using brain computer interfaces (BCI) for rehabilitation emerged relatively recently. Basically, BCI for neurorehabilitation involves the recording and decoding of local brain signals generated by the patient, as he/her tries to perform a particular task (even if imperfect), or during a mental imagery task. The main objective is to promote the recruitment of selected brain areas involved and to facilitate neural plasticity. The recorded signal can be used in several ways: (i) to objectify and strengthen motor imagery-based training, by providing the patient feedback on the imagined motor task, for example, in a virtual environment; (ii) to generate a desired motor task via functional electrical stimulation or rehabilitative robotic orthoses attached to the patient's limb ­ encouraging and optimizing task execution as well as "closing" the disrupted sensorimotor loop by giving the patient the appropriate sensory feedback; (iii) to understand cerebral reorganizations after lesion, in order to influence or even quantify plasticity-induced changes in brain networks. For example, applying cerebral stimulation to re-equilibrate inter-hemispheric imbalance as shown by functional recording of brain activity during movement may help recovery. Its potential usefulness for a patient population has been demonstrated on various levels and its diverseness in interface applications makes it adaptable to a large population. The position and status of these very new rehabilitation systems should now be considered with respect to our current and more or less validated traditional methods, as well as in the light of the wide range of possible brain damage. The heterogeneity in post-damage expression inevitably complicates the decoding of brain signals and thus their use in pathological conditions, asking for controlled clinical trials.

Increased protein glycation in cerebrospinal fluid of Alzheimer's disease.

Accumulation of advanced glycation end products occurs in the brain with ageing and was proposed to be involved in pathogenesis of Alzheimer's disease. We studied changes in the level of an early glycation product, an Amadori product, in cerebrospinal fluid (CSF) in ageing and in late-onset Alzheimer's disease. The work was carried out on 99 consecutive patients. The concentration of Amadori product in CSF correlated with CSF glucose concentration but was not changed with age (n = 70). In contrast, level of CSF Amadori product was 1.7-fold higher in Alzheimer's disease patients (n = 29) as compared with non-demented age-matched control group (n = 20; P < 0.0005), although CSF glucose concentration was similar in both groups (4.1 +/- 1.3 vs. 3.8 +/- 0.6 mmol/liter, resp.). An increased accumulation of Amadori products was found in all major proteins of CSF of Alzheimer's disease including albumin, apolipoprotein E and transthyretin. We propose that the increased early glycation of CSF proteins in the Alzheimer's patients may stimulate the formation and the consequent deposition of advanced glycation end products as well as oxidative stress in the brain.

Kinetics of apolipoprotein E isoforms-binding to the major glycosaminoglycans of the extracellular matrix.

Apolipoprotein E (apoE), a key lipid transport protein, displays a heparin-binding property that is critical in several apoE functions. The kinetics of the interaction between apoE isoforms and glycosaminoglycans (GAGs) were studied using surface plasmon resonance. The dissociation constant of equilibrium K(D) for apoE3-heparin interaction was estimated to be 12 nM for apoE3 and three common apoE isoforms revealed similar affinities for heparin. ApoE binds to GAGs in the following order: heparin>heparan sulfate>dermatan sulfate>chondroitin sulfate. The affinity parameter of the binding of low molecular weight heparins to apoE is correlated with the chain length. The effective number Z of electrostatic interactions between plasma apoE3 and heparin was assessed to be three. Metal chelators were able to diminish apoE-binding to heparin, suggesting some stabilizing effect of metal ions while reconstitution with lipids did not affect binding affinities for heparin, suggesting that the N-terminal heparin-binding site is responsible for apoE-containing lipoprotein interactions with heparin.