POS0724 GENDER DIFFERENCES IN THROMBOTIC PRIMARY ANTIPHOSPHOLIPID SYNDROME IN A LARGE COHORT OF PATIENTS FROM FOUR EUROPEAN CENTERS

Background:Autoimmune diseases occur more frequently in females and their course and severity can be affected by gender. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder in which antiphospholipid antibodies (aPL) exert a pathogenic role resulting in vascular thrombosis and/or pregnancy morbidities. Data about gender differences in thrombotic APS (t-APS) are still scarce1,2.Objectives:To evaluate the differences in frequency, disease expression and severity between females and males affected by primary t-APS.Methods:Retrospective study enrolling subjects with a formal diagnosis of primary APS (Miyakis 2006) with vascular thrombosis at onset. Women who presented with obstetric events as first aPL-related manifestation were excluded. All the patients were followed from 1967 to 2019 in four European centers: three French centers and one Italian center.Results:The study included 433 patients (68% females, 32% males). Median age at t-APS onset [31 (24-46) vs 41 (29-53) years, p<0.001] and at diagnosis [34 (27-50) vs 46 (34-57) years, p<0.001] was significantly lower in females.The most common presenting manifestations were venous thrombosis (60%) followed by arterial events (37%) and catastrophic APS (3%). Venous events were more frequent in women as compared to men (64% vs 51% p:0.012 OR:1.7 [1.1-2.5]). Sites of venous thrombosis included: limbs (35%), pulmonary (17%), cerebral (3%), portal and inferior cava (2%) and retinal (1%) veins, without gender differences. The arterial events were more frequent among men (43% vs 34% p:0.053). Strokes (27%) and myocardial infarctions (4%) were the most frequent manifestations, followed by thrombosis of limbs (2%), retina (2%) and abdominal organs (1%). Noteworthy, only men presented with visceral ischemia.During the follow-up, new thrombosis occurred in 41% of patients (179/433). 33% out of them had at least two episodes and these occurred especially among males (22% vs 10% p:0.001 OR:2.5 [1.3-4.8]). New events were mostly of the same type, but ⅓ of patients presented a switch from venous to arterial side and viceversa, with no gender differences.Complete aPL profile was available in 357 subjects: 33% had single aPL positivity, 24% double positivity and 43% triple positivity, with no differences between women and men. About 80% of the patients had a concomitant risk factor (RF) for thrombosis. Established cardiovascular RFs were more represented among men as shown in table 1. In women, estrogenic exposure was the main RFs, present in almost 40% of them.Table 1.MALESn= 137FEMALESn= 296POR [IC 95%]Traditional cardiovascular RFs, n (%)Smoke66 (48)81 (27)<0.0012.5 [1.6-3.8]Arterial hypertension59 (43)75 (25)<0.0012.2 [1.5-3.4]Dyslipidemia52 (38)72 (24)0.0041.9 [1.2-2.9]Diabetes16 (12)15 (5)0.0142.5 [1.8-5.1]Obesity13 (10)38 (13)nsOther thrombophilic factors, n (%)Estrogenic stimuli*0116 (39)-Trauma / surgery / immobilization21 (15)32 (11)nsCongenital thrombophilia9/94 (10)33/204 (16)nsData were compared using contingency tables, p value was calculated with Chi-Squared or Fisher exact test. *= hormonal therapy, pregnancy, post-partumConclusion:This gender-oriented analysis of patients with primary t-APS showed that women had the first vascular event at a younger age and mostly on the venous side, while men presented mainly with arterial events, later in life and suffered from more recurrent events. No differences were observed in the distribution of the aPL profile. The different frequency of arterial and venous events in the two groups could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, it should be underlined that some RFs, such as the use of estrogens or classic cardiovascular RFs, are exclusive or more represented in one gender rather than the other, making it difficult to assess the link of causality between gender and manifestations of t-APS.References:[1]JF de Carvalho. Rheumatol Int. 2011.[2]LJ Jara. Lupus. 2005.Disclosure of Interests:None declare

Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy

Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive–compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1–8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative–limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative–limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology

Weight Gain Is Associated with Medial Contact Site of Subthalamic Stimulation in Parkinson's Disease

The aim of our study was to assess changes in body-weight in relation to active electrode contact position in the subthalamic nucleus. Regular body weight measurements were done in 20 patients with advanced Parkinson's disease within a period of 18 months after implantation. T1-weighted (1.5T) magnetic resonance images were used to determine electrode position in the subthalamic nucleus and the Unified Parkinson's disease rating scale (UPDRS-III) was used for motor assessment. The distance of the contacts from the wall of the third ventricle in the mediolateral direction inversely correlated with weight gain (r = −0.55, p<0.01) and with neurostimulation-related motor condition expressed as the contralateral hemi-body UPDRS-III (r = −0.42, p<0.01). Patients with at least one contact within 9.3 mm of the wall experienced significantly greater weight gain (9.4±(SD)4.4 kg, N = 11) than those with both contacts located laterally (3.9±2.7 kg, N = 9) (p<0.001). The position of the active contact is critical not only for motor outcome but is also associated with weight gain, suggesting a regional effect of subthalamic stimulation on adjacent structures involved in the central regulation of energy balance, food intake or reward

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

Short-term locomotor adaptation to a robotic ankle exoskeleton does not alter soleus Hoffmann reflex amplitude

<p>Abstract</p> <p>Background</p> <p>To improve design of robotic lower limb exoskeletons for gait rehabilitation, it is critical to identify neural mechanisms that govern locomotor adaptation to robotic assistance. Previously, we demonstrated soleus muscle recruitment decreased by ~35% when walking with a pneumatically-powered ankle exoskeleton providing plantar flexor torque under soleus proportional myoelectric control. Since a substantial portion of soleus activation during walking results from the stretch reflex, increased reflex inhibition is one potential mechanism for reducing soleus recruitment when walking with exoskeleton assistance. This is clinically relevant because many neurologically impaired populations have hyperactive stretch reflexes and training to reduce the reflexes could lead to substantial improvements in their motor ability. The purpose of this study was to quantify soleus Hoffmann (H-) reflex responses during powered versus unpowered walking.</p> <p>Methods</p> <p>We tested soleus H-reflex responses in neurologically intact subjects (n=8) that had trained walking with the soleus controlled robotic ankle exoskeleton. Soleus H-reflex was tested at the mid and late stance while subjects walked with the exoskeleton on the treadmill at 1.25 m/s, first without power (first unpowered), then with power (powered), and finally without power again (second unpowered). We also collected joint kinematics and electromyography.</p> <p>Results</p> <p>When the robotic plantar flexor torque was provided, subjects walked with lower soleus electromyographic (EMG) activation (27-48%) and had concomitant reductions in H-reflex amplitude (12-24%) compared to the first unpowered condition. The H-reflex amplitude in proportion to the background soleus EMG during powered walking was not significantly different from the two unpowered conditions.</p> <p>Conclusion</p> <p>These findings suggest that the nervous system does not inhibit the soleus H-reflex in response to short-term adaption to exoskeleton assistance. Future studies should determine if the findings also apply to long-term adaption to the exoskeleton.</p