Suleimy Cristina Mazin

Ischemic myocardial injuries after cardiac malformation repair in infants may be associated with oxidative stress mechanisms

BACKGROUND Despite advances in pediatric cardiac surgery, perioperative myocardial injury can be the major determinant of postoperative dysfunction after cardiac surgery. This study investigated the pathology-related differences in 29 infants with congenital heart disease that led to death. The infants were treated at the University Hospital of Ribeirão Preto, Brazil. METHODS The patients were divided into four groups: Group 1, 16 infants who underwent operations for congenital heart disease on cardiopulmonary bypass; Group 2, four infants who underwent off-cardiopulmonary bypass operations for congenital heart disease; Group 3, nine infants who died from congenital heart disease prior to surgical treatment; and Group 4 (control group), five infants with no congenital heart disease and who died from other causes. The myocardial injuries and oxidative stress mechanisms were assessed by histopathology and immunohistochemistry and were quantified by morphometrical analyses. RESULTS Contraction band necrosis and dystrophic calcification were found primarily in infants of Group 1. Coagulation necrosis and healing were prominent in Group 2, while infants without repair (Group 3) showed mainly colliquative myocytolysis. Apoptotic cells were more prominent in the operative groups. The control group showed no significant myocardial lesions. Lipid peroxidation was the principal mechanism of oxidative stress accounting for the myocardial lesions. CONCLUSION The diversity of the lesions observed in these hearts seemed to indicate a large spectrum of cell damage due to inadequate myocardial perfusion, especially when these infants underwent surgery. Oxidative mechanisms could be a common mediator in the pathogenesis of myocardial injuries, mediated by peroxidation of the membrane phospholipids and resulting in changes in the permeability of the cell membrane, cell death, and intracellular calcium overload. Furthermore, an immature and often hypertrophied myocardium may promote unfavorable conditions, leading to heart failure and a lethal outcome.

Verticality Perceptions Associate with Postural Control and Functionality in Stroke Patients

Deficits of postural control and perceptions of verticality are disabling problems observed in stroke patients that have been recently correlated to each other. However, there is no evidence in the literature confirming this relationship with quantitative posturography analysis. Therefore, the objectives of the present study were to analyze the relationship between Subjective Postural Vertical (SPV) and Haptic Vertical (HV) with posturography and functionality in stroke patients. We included 45 stroke patients. The study protocol was composed by clinical interview, evaluation of SPV and HV in roll and pitch planes and posturography. Posturography was measured in the sitting and standing positions under the conditions: eyes open, stable surface (EOSS); eyes closed, stable surface (ECSS); eyes open, unstable surface (EOUS); and eyes closed, unstable surface (ECUS). The median PV in roll plane was 0.34° (-1.44° to 2.54°) and in pitch plane 0.36° (-2.72° to 2.45°). The median of HV in roll and pitch planes were -0.94° (-5.86° to 3.84°) and 3.56° (-0.68° to 8.36°), respectively. SPV in the roll plane was correlated with all posturagraphy parameters in sitting position in all conditions (r = 0.35 to 0.47; p < 0.006). There were moderate correlations with the verticality perceptions and all the functional scales. Linear regression model showed association between speed and SPV in the roll plane in the condition EOSS (R2 of 0.37; p = 0.005), in the condition ECSS (R2 of 0.13; p = 0.04) and in the condition EOUS (R2 of 0.22; p = 0.03). These results suggest that verticality perception is a relevant component of postural control and should be systematically evaluated, particularly in patients with abnormal postural control.

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.

How Many Patients Become Functionally Dependent after a Stroke? A 3-Year Population-Based Study in Joinville, Brazil

The decrease in stroke mortality will increase the burden of survivors with functional dependence (FD). The aim of this study was to evaluate how many patients become functionally dependent over 3 years after an incident event in Joinville, Brazil. The proportion of FD (defined as a modified Rankin score 3 to 5) among stroke survivors from the Joinville Stroke Registry was assessed using a validated telephone interview. Incidence of FD after stroke in Joinville in one year was 23.24 per 100,000 population. The overall proportion of FD among stroke survivors at discharge was 32.7%. Of 303 patients with first-ever ischaemic stroke (IS), one-third were FD at discharge, and 12%, 9% and 8%, respectively at 1, 2 and 3 years. Among 37 patients with haemorrhagic stroke (HS), 38% were dependent at discharge, 16% after 1 and 2 years and 14% after 3. Among 27 patients with subarachnoid haemorrhage (SAH), 19% were dependent at discharge and 4% from 1 to 3 years. Among IS subtypes, cardioembolic ones had the worst risk of FD. (RR 19.8; 95% CI: 2.2 to 175.9). Our results showed that one-third of stroke survivors have FD during the first year after stroke in Brazil. Therefore, a city with half a million people might expect 120 new stroke patients with FD each year.

Intravenous rtPA versus mechanical thrombectomy in acute ischemic stroke: A historical cohort in Joinville, Brazil

Groundbreaking results concerning ischemic stroke (IS) hyperacute treatment worldwide were published in 2014 and 2015. We aimed to compare functional status after 3 months in patients treated with intra-arterial thrombectomy (IAT) and those treated with intravenous thrombolysis (IVT) alone in Joinville, Brazil. From the Joinville Stroke Registry, we extracted and compared all consecutive IVT patients treated with r-tPA within 4.5 h in the period 2009–2011 versus all consecutive IAT treated within 6 h with the Solitaire FR device plus IVT in the period 2012–2014. We registered 82 patients in the IVT group and 31 patients in the IAT group. At hospital admission, patients in the IAT group were significantly younger (p < 0.001), had a higher educational level (p = 0.001), had a slightly higher prevalence of atrial fibrillation (p = 0.057) and had more severe strokes measured by the NIH stroke scale (p = 0.011). After 90 days, 45% of patients in the IAT group and 27% in the IVT group were independent (0–1 points) according to the modified Rankin scale (adjusted odds ratio: 4.53; 95% CI: 1.22 to 16.75). Symptomatic hemorrhage was diagnosed in 10% of patients in both groups (p = 1.0). The 90-day case-fatality was 39% (32/82) in the IVT group and 26% (8/31) in the IAT group (p = 0.27). In this small cohort, a greater rate of functional independence was achieved in patients treated with IAT plus IVT, compared with patients treated with IVT lysis alone. Our “real-world” findings are consistent with results of controlled, randomized clinical trials.

Center of Pressure Speed Changes with tDCS Versus GVS in Patients with Lateropulsion after Stroke

Weoffer this letter to spark discussion about potential transcranial methods to augment rehabilitation to ameliorate lateropulsion after stroke. Patients with lateropulsion after stroke, also known as ‘pusher syndrome,’ actively push themselves to the weak side and resist passive correction of the posture to the vertical upright [1]. Various lesion sites along pathways which formulate subjective perceptions of verticality have been implicated in lateropulsion. Transcranial direct current stimulation (tDCS) or galvanic vestibular stimulation (GVS) over parts of the impaired pathways may change seated center of pressure for patients with lateropulsion and provide insight into the nature of the lesioned pathway. The parietal-insular vestibular cortex (PIVC) is a multi-modal cortical region that synthesizes sensory input from vestibular, somatosensory, and visual systems to allow dynamic regulation of postural orientation [2]. In addition, trans-mastoidal galvanic vestibular stimulation (GVS) may provide a means of augmenting vestibular neural systems controlling posture and balance. Both tDCS and GVS could be used to impact posture before, during or after physical therapy sessions [3] because they are portable, safe and well-tolerated. We tested the hypotheses that anodal upregulation on the lesion side via tDCS over the area of the PIVC or GVS might change tonic seated posture, as measured by the speed of the center of pressure, in the frontal plane. Nine patients with ischemic strokewith Burke Lateropulsion Scale (BLS) scores of 2 or greater (BLS range 0 to 17, 17 =maximal lateropulsion) [4] admitted to an inpatient rehabilitation facility participated in this pilot study.1 Patients were: at least one week post ischemic stroke, able to sit for at least 25minutes, cleared by admitting physician for study participation, and able to verbalize. Excluded patients had: hemorrhagic stroke, history of seizure or receiving medications that may lower seizure threshold, implanted cardiac devices, prior craniotomy, or cervical fusions with metallic implant. tDCS and GVS were delivered using a Starstim current limited stimulator (Neuroelectrics®, Cambridge, MA, USA) via two 25 cm2 saline-soaked sponge electrodes. Patients were blinded to randomized stimulation sequences on different days: A) bipolar-balanced tDCS anode over the ipsilesional PIVC, defined as the circumcenter of a triangle defined by EEG locations P3, C3, T3 for left brain lesions; and P4, C4, T4 for right brain lesions. The cathode was placed in the same location on the contralesional side; B) tDCS with anode over the ipsilesional PIVC as for condition A, but with the cathode placed over the contralateral supraorbital region; C) trans-mastoidal GVS with anode over the mastoid on the lesion side; D) sham stimulation with electrodes randomized to one of the above montages but with 30-sec ramp-up to 2 mA then immediate ramp down to 0 mA for the remainder of the test period. Patients were seated in a specialized chair mounted on an AMTITM (Advanced Mechanical Technology, Inc., Watertown, MA, USA) force plate, which measured the center of pressure (COP) of the subject over time. AcqKnowledge® software (BioPac® Systems, Inc., Goleta, CA, USA) collected data. A 4th order, low-pass Butterworth filter with a cut-off frequency of 10 Hz was applied. Baseline assessments of COP were recorded for 1 min. A stimulation protocol was initiated and subsequent 1-min recordings of COP were taken at 5, 10, and 15 min. Stimulation was stopped and a final 1-min recording was taken at 20 min. Data were analyzed using a linear mixed-effect model with time (T0 to T4) and stimulation conditions (A, B, C, and D) as the fixed effects and subject as random effect. The primary outcome variable, mean speed of COP in the roll plane (COP-Xs), was operationally defined as the average speed (cm/s) of oscillation of the displacement of COP [5]. Means were compared using orthogonal contrasts via t statistics (p < .05, SAS System version 9.2 (SAS Institute Inc., Cary, NC, USA)). The Fig. 1 illustrates a small but significant increase in mean COP-X speed for Condition A versus D at T1 ( X cm/s diff = 0 13 . , 95% CI 0.002 to 0.25, p = .04, effect size = 0.22). Mean COP-Xs did not differ significantly for conditions B and C compared to sham condition at any of the time intervals studied. Mean COP-Xs was also significantly different for condition A between time points T0 and T1 (X cm/s diff = 0 17 . , 95% CI 0.05 to 0.29, p < .001, effect size = 0.53). Mean COP-Xs did not differ significantly between respective time points for montages B, C and D. We need to be conservative about the interpretation of these results due to the small sample size. However, the findings open the possibility that anodal stimulation of the affected PIVC and cathodal inhibition of the contralesional “disinhibited” PIVC may reduce the contralesional tonic bias of seated posture of patients with poststroke lateropulsion. Restoration of “normal” bilateral PIVC balance may provide an opportunity for training more accurate postural control at least for a brief initial interval of tDCS. These findings also indicate that vestibular stimulation via GVS did not change mean COP-Xs as explained in previous studies with healthy subjects [6,7]. The lack of change via GVS may strengthen the argument that postural awareness and control are cortical functions that prioritize visual and proprioceptive sensory input over direct vestibular sensory input. The current density used in our study (2 mA/25 cm2 or 0.08 mA/cm2), as described previously [6], may have been too weak to produce an adequate, prolonged neuronal response. These observations are important to publicize as they may lead to the next step in study design. We plan to explore the use of 2 mA 1 The study was approved by the Committee on Human Rights in Research (IRB) of the institution. Informed consent was obtained both from the patient and their next-of-kin or health care proxy. ARTICLE IN PRESS

The Informal Caregiver Burden Assessment Questionnaire: validation for Brazil

OBJECTIVES to analyze the dimensionality, convergent construct validity and internal consistency of the Informal Caregiver Burden Assessment Questionnaire (QASCI) after its semantic adaptation to Brazil. METHOD this methodological study was developed with 132 informal caregivers of elders who are dependent of help for basic or instrumental activities of daily living, in a capital city in Northeast Brazil. Quality of life measures related to health, anxiety and depression were used in the analysis of the convergent construct validity of the QASCI. RESULTS the results of the instrument construct validation evidenced statistically significant correlations with the three measures. The confirmatory factor analysis evidenced good adjustment of the theoretical model of seven factors (domains) of the version used in the group studied. Cronbachs alpha for the scale total was 0.92. CONCLUSION the Brazilian version of the QASCI was considered to be valid and reliable for assessing the burden of informal elder caregivers.

Questionário de Avaliação da Sobrecarga do Cuidador Informal: validação para o Brasil

OBJECTIVES to analyze the dimensionality, convergent construct validity and internal consistency of the Informal Caregiver Burden Assessment Questionnaire (QASCI) after its semantic adaptation to Brazil. METHOD this methodological study was developed with 132 informal caregivers of elders who are dependent of help for basic or instrumental activities of daily living, in a capital city in Northeast Brazil. Quality of life measures related to health, anxiety and depression were used in the analysis of the convergent construct validity of the QASCI. RESULTS the results of the instrument construct validation evidenced statistically significant correlations with the three measures. The confirmatory factor analysis evidenced good adjustment of the theoretical model of seven factors (domains) of the version used in the group studied. Cronbachs alpha for the scale total was 0.92. CONCLUSION the Brazilian version of the QASCI was considered to be valid and reliable for assessing the burden of informal elder caregivers.

Normative data for human postural vertical: A systematic review and meta-analysis

Perception of verticality is required for normal daily function, yet the typical human detection error range has not been well characterized. Vertical misperception has been correlated with poor postural control and functionality in patients after stroke and after vestibular disorders. Until now, all the published studies that assessed Subjective Postural Vertical (SPV) in the seated position used small groups to establish a reference value. However, this sample size does not represent the healthy population for comparison with conditions resulting in pathological vertical. Therefore, the primary objective was to conduct a systematic review with meta-analyses of Subjective Postural Vertical (SPV) data in seated position in healthy adults to establish the reference value with a representative sample. The secondary objective was to investigate the methodological characteristics of different assessment protocols of SPV described in the literature. A systematic literature search was conducted using Medline, EMBASE, and Cochrane libraries. Mean and standard deviation of SPV in frontal and sagittal planes were considered as effect size measures. Sixteen of 129 identified studies met eligibility criteria for our systematic review (n = 337 subjects in the frontal plane; n = 187 subjects in sagittal plane). The meta-analyses measure was estimated using the pooled mean as the estimator and its respective error. Mean reference values were 0.12°±1.49° for the frontal plane and 0.02°±1.82° for the sagittal plane. There was a small variability of the results and this systematic review resulted in representative values for SPV. The critical analysis of the studies and observed homogeneity in the sample suggests that the methodological differences used in the studies did not influence SPV assessment of directional bias in healthy subjects. These data can serve as a reference for clinical studies in disorders of verticality.

Sinusoidal Transcranial Direct Current Versus Galvanic Vestibular Stimulation for Treatment of Lateropulsion Poststroke

OBJECTIVE To compare the effects of Transcranial Direct Current Stimulation (tDCS) versus Galvanic Vestibular Stimulation (GVS) on Lateropulsion following stroke. METHODS Patients with Stroke and Burke Lateropulsion Scale (BLS) scores greater than or equal to 2 gave informed consent to receive sinusoidal 1 Hz DC (0-2 mA) anodal stimulation over the affected parietal cortex versus similar GVS with ipsilesional mastoidal anode. Seated haptic center of pressure (COP-X) was measured using an AMTI analog-to-digital forceplate. An inclinometer (Biopac ) measured lateral thoracic tilt. COP-X Power Spectra were analyzed over 3 frequency intervals: 0-.3 Hz, .3-1 Hz, and 1-3 Hz. RESULTS Six males/4 females age 66 ± 9.5 standard deviation with admission BLS scores of 5.4 ± 3.7 within 8.6 ± 8.1 days poststroke were enrolled. COP-X medial-lateral speed increased for both the tDCS and the GVS protocols compared to sham condition. Fourier Analysis of COP-X velocity for 0-.3 Hz responses showed a significant increase for tDCS stimulation. The .3-1 Hz responses for the tDCS condition were decreased from baseline. Lateral thoracic tilt showed significant improvement for tDCS compared to Sham stimulation at 10 minutes and for GVS versus Sham at 15 minutes. DISCUSSION Anodal tDCS over the ipsilesional PIVC increases low frequency postural responses usually attributed to visual control with down regulation of median frequency vestibular responses, biasing postural control toward more dependence on visual as opposed to vestibular control. CONCLUSIONS 2 mA sinusoidal 1 Hz anodal tDCS over the ipsi-lesional PIVC or similar ipsi-lesional anodal GVS improve Lateropulsion following stroke.