An EEG index of sensorimotor interhemispheric coupling after unilateral stroke: clinical and neurophysiological study

Brain connectivity has been employed to investigate on post‐stroke recovery mechanisms and assess the effect of specific rehabilitation interventions. Changes in interhemispheric coupling after stroke have been related to the extent of damage in the corticospinal tract (CST) and thus, to motor impairment. In this study, we aimed at defining an index of interhemispheric connectivity derived from electroencephalography (EEG), correlated with CST integrity and clinical impairment. Thirty sub‐acute stroke patients underwent clinical and neurophysiological evaluation: CST integrity was assessed by Transcranial Magnetic Stimulation and high‐density EEG was recorded at rest. Connectivity was assessed by means of Partial Directed Coherence and the normalized Inter‐Hemispheric Strength (nIHS) was calculated for each patient and frequency band on the whole network and in three sub‐networks relative to the frontal, central (sensorimotor) and occipital areas. Interhemipheric coupling as expressed by nIHS on the whole network was significantly higher in patients with preserved CST integrity in beta and gamma bands. The same index estimated for the three sub‐networks showed significant differences only in the sensorimotor area in lower beta, with higher values in patients with preserved CST integrity. The sensorimotor lower beta nIHS showed a significant positive correlation with clinical impairment. We propose an EEG‐based connectivity index which is a measure of the interhemispheric cross‐talking and correlates with functional motor impairment in subacute stroke patients. Such index could be employed to evaluate the effects of training aimed at re‐establishing interhemispheric balance and eventually drive the design of future connectivity‐driven rehabilitation interventions.     

Mechanisms inducing low bone density in duchenne muscular dystrophy in mice and humans

Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro–computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild‐type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro‐osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL‐6) was increased compared with wild‐type mice. Likewise, DMD patients showed low bone mineral density (BMD) Z‐scores and high bone‐resorption marker and serum IL‐6. Human primary osteoblasts from healthy donors incubated with 10% sera from DMD patients showed decreased nodule mineralization. Many osteogenic genes were downregulated in these cultures, including osterix and osteocalcin, by a mechanism blunted by an IL‐6‐neutralizing antibody. In contrast, the mRNAs of osteoclastogenic cytokines IL6, IL11, inhibin‐βA, and TGFβ2 were increased, although only IL‐6 was found to be high in the circulation. Consistently, enhancement of osteoclastogenesis was noted in cultures of circulating mononuclear precursors from DMD patients or from healthy donors cultured in the presence of DMD sera or IL‐6. Circulating IL‐6 also played a dominant role in osteoclast formation because ex vivo wild‐type calvarial bones cultured with 10% sera of MDX mice showed increase osteoclast and bone‐resorption parameters that were dampen by treatment with an IL‐6 antibody. These results point to IL‐6 as an important mediator of bone loss in DMD and suggest that targeted anti‐IL‐6 therapy may have a positive impact on the bone phenotype in these patients. © 2011 American Society for Bone and Mineral Research     

Isokinetic flexion strength recovery after ACL reconstruction: a comparison between all inside graft-link technique and full tibial tunnel technique

Introduction: Recently, a new minimally invasive single bundle technique for anatomic ACL reconstruction has been described, called the ‘All-Inside graft-link technique’. One of the advantages of this procedure is the reduced morbidity at the donor site as the graft choice is the quadrupled semitendinosus, thus sparing the gracilis tendon. The aim of this study was to evaluate isokinetic flexion strength recovery in patients who underwent a gracilis sparing technique compared to those with a full-tibial tunnel technique using a doubled gracilis and semitendinosus tendons (DGST) graft.

Methods: Patients were divided into two groups: Group A (22 patients) who underwent ACL reconstruction performed with an All-Inside graft-link technique; Group B (22 patients) who underwent ACL reconstruction with an Out-In technique and DGST graft. At a mean follow-up of 13 months, quadriceps and hamstring isokinetic peak torque deficits were recorded.

Results: In group A, the mean side to side peak torque flexion difference between the operated and non-operated limbs was ?3% and the mean torque at 30° was ?7.5% at high angular velocity (180°/sec); the mean peak flexion torque was 7.2% and the mean torque at 30° was 3.1% at low angular velocity (60°/sec).

In group B, the mean side to side peak flexion torque was ?3.5% and the mean torque at 30° was ?7.6% at high angular velocity (180°/sec); the mean peak flexion torque was ?7.2% and the mean torque at 30° was ?11% at low angular velocity (60°/sec).

A statistically significant difference was found between the two groups at lower angular velocity both for the mean peak flexion torque and the mean torque at 30° (p = 0.009), with better results in the study group.

Discussion/conclusion: Gracilis sparing technique is a minimally invasive technique for ACL reconstruction and yielded a significantly better flexion strength recovery at lower angular velocity compared to a full tibial tunnel technique with DGST for ACL reconstruction.     

Diagnostic accuracy of ICD-9 code 780.2 for the identification of patients with syncope in the emergency department

Purpose

Syncope is a common condition that affects individuals of all ages and is responsible for 1–3% of all emergency department (ED) visits. Prospective studies on syncope are often limited by the exiguous number of subjects enrolled. A possible alternative approach would be to use of hospital discharge diagnoses from administrative databases to identify syncope subjects in epidemiological observational studies. We assessed the accuracy of the International Classification of Diseases, Ninth Revision (ICD-9) code 780.2 “syncope and collapse” to identify patients with syncope.

Methods

Patients in two teaching hospitals in Milan, Italy with a triage assessment for ED access that was possibly related to syncope were recruited in this study. We considered the index test to be the attribution of the ICD-9 code 780.2 at ED discharge and the reference standard to be the diagnosis of syncope by the ED physician.

Results

The sensitivity, specificity, positive and negative predictive values of the ICD-9 code 780.2 to identify patients with syncope were 0.63 (95% confidence interval [CI] 0.58–0.67), 0.98 (95% CI 0.98–0.99), 0.83 (95% CI 0.79–0.87) and 0.95 (95% CI 0.94–0.95), respectively.

Conclusions

The moderate sensitivity of ICD-9 code 780.2 should be considered when the code is used to identify patients with syncope through administrative databases.

     

Early nocturnal blood pressure changes in diabetic autonomic neuropathy assessed by Fourier series

The 24 h periodic pattern of blood pressure was studied in 44 patients with diabetes mellitus (14 type 1, 30 type 2; mean duration of disease 6.5 ± 1.8 years) in good metabolic control but with abnormal cardiovascular reflex responses; of these 21 were normotensive and 23 hypertensive. All had abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manoeuvre and postural hypotension. Two sex- and agematched groups, consisting of 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, were studied as controls. Each patient underwent ambulatory blood pressure monitoring for at least 24 h, using an auscultatory automatic device. Data were analysed using the sum of three periodic functions (Fourier partial sum). In the diabetic normotensive groups, the absolute blood pressure fell to its night-time minimum more rapidly, and increased to its morning maximum more slowly, in those with abnormal cardiovascular reflexes than in the controls (nightly blood pressure decrease –5.8/–4.7 vs. –3.8/–4.0 mmHg/h; increase 4.7/3.6 vs. 5.9/6.1 mmHg/h). The same behaviour was found in both hypertensive groups but the amplitude of the differences was more marked (blood pressure nocturnal decrease –7.7/–7.1 vs. –4.3/–3.9 mmHg/h; increase 3.2/2.1 vs. 5.8/4.3 mmHg/h). This analysis of 24 h ambulatory blood pressure data may be of value in diagnosis and evaluation of autonomic deficits.     

Boosting the traditional physiotherapist approach for stroke spasticity using a sensorized ankle foot orthosis: a pilot study

Background: Spasticity is a motor disorder that is commonly treated manually by a physical therapist (PhT) stretching the muscles. Recent data on learning have demonstrated the importance of human-to-human interaction in improving rehabilitation: cooperative motor behavior engages specific areas of the motor system compared with execution of a task alone.

Objectives: We hypothesize that PhT-guided therapy that involves active collaboration with the patient (Pt) through shared biomechanical visual biofeedback (vBFB) positively impacts learning and performance by the Pt during ankle spasticity treatment. A sensorized ankle foot orthosis (AFO) was developed to provide online quantitative data of joint range of motion (ROM), angular velocity, and electromyographic activity to the PhT and Pt during the treatment of ankle spasticity.

Methods: Randomized controlled clinical trial. Ten subacute stroke inpatients, randomized into experimental (EXP) and control (CTRL) groups, underwent six weeks of daily treatment. The EXP group was treated with an active AFO, and the CTRL group was given an inactive AFO. Spasticity, ankle ROM, ankle active and passive joint speed, and coactivation index (CI) were assessed at enrollment and after 15–30 sessions.

Results: Spasticity and CI (p < 0.005) decreased significantly after training only in the EXP group, in association with a significant rise in active joint speed and active ROM (p < 0.05). Improvements in spasticity (p < 0.05), active joint speed (p < 0.001), and CI (p < 0.001) after treatment differed between the EXP and CTRL groups.

Conclusions: PhT–Pt sharing of exercise information, provided by joint sensorization and vBFB, improved the efficacy of the conventional approach for treating ankle spasticity in subacute stroke Pts.     

Interhemispheric Connectivity Characterizes Cortical Reorganization in Motor-Related Networks After Cerebellar Lesions

Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30–40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general.     

Sex-dependent and differential responses to acute restraint stress of corticotropin-releasing factor-producing neurons in the rat paraventricular nucleus, central amygdala, and bed nucleus of the stria terminalis

Male and female rodents respond differently to acute stress. We tested our hypothesis that this sex difference is based on differences in stress sensitivity of forebrain areas, by determining possible effects of a single acute psychogenic stressor (1-hr restraint stress) on neuronal gene expression (c-Fos and FosB immunoreactivities), storage of corticotropin-releasing factor (CRF) immunoreactivity, and CRF production (CRF mRNA in situ hybridization) as well as the expression of genes associated with epigenetic processes (quantitative RT-PCR) in the rat paraventricular nucleus (PVN), the oval and fusiform subdivisions of the bed nucleus of the stria terminalis (BSTov and BSTfu, respectively), and the central amygdala (CeA), in both males and females. Compared with females, male rats responded to the stressor with a stronger rise in corticosterone titer and a stronger increase in neuronal contents of c-Fos, CRF mRNA, and CREB-binding protein mRNA in the PVN. In the BSTov, females but not males showed an increase in c-Fos, whereas the CRF mRNA content was increased in males only. In the BSTfu, males and females showed similar stress-induced increases in c-Fos and FosB, whereas in the CeA, both sexes revealed similar increases in c-Fos and in CRF mRNA. We conclude that male and female rats differ in their reactivity to acute stress with respect to possibly epigenetically mediated (particularly in the PVN) neuronal gene expression and neuropeptide dynamics (PVN and BSTov) and that this difference may contribute to the sex dependence of the animal's physiological and behavioral responses to an acute stressor.