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Genomic insights into stroke recovery: cross-phenotype associations.

Stroke is a major cause of long-term disability with variable recovery. While clinical factors such as initial severity play a role, genetic factors are increasingly recognized as important contributors to stroke recovery. Genotype studies are generally focused on a single post-stroke behavioural domain, but some genes might relate to broad mechanisms of plasticity. This study therefore aimed to identify cross-phenotypic genetic variants associated across two or more stroke recovery domains. DNA from Stroke, Stress, Rehabilitation, and Genetics study participants was genotyped, resulting in 9 814 610 variants. In order to examine cross-phenotypic results, we first conducted genome-wide association studies on the six recovery domains: motor (grip force), cognition (Telephone Montreal Cognitive Assessment), depression (Patient Health Questionnaire-8), stress (Primary Care Post-Traumatic Stress Disorder Screen), functional status (Stroke Impact Scale-Activities of Daily Living), and disability (modified Rankin Scale 0-2 versus 3-6), some of which were tested longitudinally, yielding nine phenotypes. Models were adjusted for age, sex, initial severity (NIH Stroke Scale score), and ancestry. Cross-phenotype associations were identified by evaluating single nucleotide polymorphisms (SNPs) associated (P < 5e-5) with multiple phenotypes. To determine how these genetic variants may relate to biological mechanisms of recovery, we conducted gene enrichment analyses. Participants (n = 565, 59% male) had mild-moderate initial stroke severity (median acute NIH Stroke Scale score = 4). After accounting for the correlation structure among the nine phenotypes, we observed 319 cross-phenotypic SNPs, 3.45 times the expected number. Five of the cross-phenotypic SNPs were linked to genes relevant to neural development, function and plasticity, e.g. ERICH1 (rs11778883-C), FOX3 (rs55726768-G), LIFR-AS1 (rs76401391-T), RPS6KA2 (rs113518460-C) and TUBGCP2 (rs147150392-C), as were enrichments in RAB5-EEA1, CTNNA1-CTNNB1, CIN85-SH3GL2 and ELMO1-DOCK2 complexes. Multiple gene enrichments were found, e.g. Stroke Impact Scale-Activities of Daily Living and Patient Health Questionnaire 8 at 3 months were enriched for CREB phosphorylation, which is important for long-term potentiation. We identified cross-phenotypic SNPs associated with multiple behavioural domains of stroke recovery. Some of these genes encode, or regulate, druggable proteins. These genetic factors are not well captured by clinical or neuroimaging assessments and so provide a unique window into stroke recovery. These findings, if validated, suggest that some genes may be broadly important to stroke recovery.

GWAS↗

The interacting effects of cognitive demand and recovery of postural stability in balance-impaired elderly persons.

BACKGROUND: Although postural recovery is attentionally demanding in healthy elderly persons, an inability to recover balance due to competition for attentional resources between the postural system and a second task could contribute to falls in older adults with poor balance. This study examined the attentional demands of balance recovery from a mild postural disturbance in balance-impaired elderly persons. A second purpose of this research was to determine the effect of performing a cognitive task on the recovery of balance in balance-impaired elderly persons. METHODS: Fifteen healthy older adults and 13 older adults with clinical balance impairment were exposed to balance disturbances by means of sudden movement of a platform on which they stood. A dual-task paradigm where postural recovery served as the primary task and verbal reaction time to auditory tones served as the secondary task was used to assess attentional demand. To determine the effect of the cognitive task on postural recovery, kinetic, kinematic, and neuromuscular measures of a feet-in-place response were investigated. RESULTS: Balance recovery using a feet-in-place response was attentionally demanding in both groups of older adults and was more demanding in balance-impaired than in healthy elderly persons. With the concurrent performance of a cognitive task, balance-impaired elderly persons took longer to stabilize their center of pressure and regain balance than in a single task, while healthy elderly persons showed no change between conditions. In addition, only balance-impaired elderly individuals had a greater center-of-pressure resultant velocity during recovery in a dual-task compared with a single-task situation. CONCLUSIONS: The ability to recover balance using a feet-in-place response was more attentionally demanding in balance-impaired than in healthy elderly persons. The recovery of balance was also slower and less efficient in balance-impaired elderly persons when simultaneously performing a cognitive task, whereas the ability of healthy elderly individuals to recover was not influenced by concurrent task demands. This suggests that dual-task performance may contribute to postural instability and falls in balance-impaired elderly individuals.

Accidental Falls↗

Recovery after anesthesia with remifentanil combined with propofol, desflurane, or sevoflurane for otorhinolaryngeal surgery.

UNLABELLED: Because no previous investigation has directly compared the combination of remifentanil (REM) and a hypnotic with that of REM and the newer volatile anesthetics, we studied recovery characteristics and patient satisfaction after the combination of REM with propofol (PRO), desflurane (DES), or sevoflurane (SEVO). One hundred twenty patients were randomly assigned to receive anesthesia with either REM/PRO, REM/DES, REM/SEVO, or thiopental/alfentanil/isoflurane/N(2)O (control group) for ear, nose, and throat surgery (n = 30 each). In the REM groups, the dosage of PRO (75 microg. kg(-1). min(-1)), and of DES or SEVO (0.5 minimum alveolar anesthetic concentration) was kept unchanged, and REM was titrated to hemodynamic response. The control group was managed according to standard practice. Early recovery (times to eye opening, extubation, and statement of name and date of birth) was predictably faster and more complete in the REM groups compared with the control group. However, late recovery (times to discharge from postanesthesia care unit and hospital) and overall patient satisfaction were not different among groups. No clinically relevant differences existed among the three REM groups. In conclusion, the combination of REM infusion with small-dose DES, SEVO, or PRO is characterized by predictably rapid, early recovery. However, late recovery and patient satisfaction are comparable to a conventional anesthetic technique. IMPLICATIONS: Remifentanil anesthesia, combined with small-dose propofol, desflurane, or sevoflurane, enables predictably fast and smooth early recovery after ear, nose, and throat surgery. Despite such faster, early recovery and less need for postoperative analgesic and antiemetic medication, late recovery was comparable among the remifentanil combination groups and the control group.

Adolescent↗

Postoperative recovery after desflurane, propofol, or isoflurane anesthesia among morbidly obese patients: a prospective, randomized study.

UNLABELLED: Recovery from anesthesia might be compromised in obese patients. Because of its pharmacological properties, desflurane might allow rapid postoperative recovery for these patients. We compared postoperative recovery for 36 obese patients randomized to receive either desflurane, propofol, or isoflurane to maintain anesthesia during laparoscopic gastroplasties. Anesthesia was induced with propofol and succinylcholine IV and was maintained with rocuronium, alfentanil, inhaled nitrous oxide, and the study drug. Immediate recovery (i.e., times from the discontinuation of anesthesia to tracheal extubation, eye opening, and the ability to state one's name) was measured. At the time of postanesthesia care unit (PACU) admission, arterial saturation and the ability of patients to move were recorded. In the PACU, intermediate recovery was measured by using sedation and psychometric evaluations, 30, 60, and 120 min postoperatively. Data were compared between groups by using the Kruskal-Wallis and chi(2) tests. Results were reported as means +/- SD. P: < 0.05, compared with desflurane, was considered significant. Immediate recovery occurred faster, and was more consistent, after desflurane than after propofol or isoflurane (times to extubation were 6 +/- 1 min, 13 +/- 8 min [P: < 0.05, compared with desflurane], and 12 +/- 6 min [P: < 0.05, compared with desflurane], respectively). At PACU admission, SpO(2) values were significantly higher and patient mobility was significantly better after desflurane than after isoflurane or propofol. Sedation was significantly less pronounced with desflurane at 30 and 120 min postoperatively. In morbidly obese patients, postoperative immediate and intermediate recoveries are more rapid after desflurane than after propofol or isoflurane anesthesia. This advantage of desflurane persists at least for 2 h after surgery and is associated with both an improvement in patient mobility and a reduced incidence of postoperative desaturation. IMPLICATIONS: In morbidly obese patients, postoperative immediate and intermediate recoveries are more rapid and consistent after desflurane than after propofol or isoflurane anesthesia.

Adult↗

Pain as a factor complicating recovery and discharge after ambulatory surgery.

UNLABELLED: Pain complicates the recovery process after ambulatory surgery. We surveyed 175 ambulatory surgery patients to determine pain severity, analgesic use, relationship of pain to duration of recovery, and the relative importance of various factors to predicting these outcomes. Multivariate regression analysis was used to determine unique contributions of predictor variables to outcome. Surgical procedures included knee arthroscopy (n = 50), hernia surgery (n = 25), pelvic laparoscopy (n = 25), transvaginal uterine surgery (n = 25), surgery for breast disease (n = 25), and plastic surgery (n = 25). Maximum pain (on a scale of 0-10) varied from 2.3 +/- 0.5 to 5.1 +/- 0.5 (mean +/- SE), depending on surgical procedure; 24% of patients had pain scores of > or =7, and 24% were delayed in Phase 1 recovery by pain. Pain scores were lower if local anesthetic or ketorolac was administered intraoperatively (22% and 26% respectively). Fentanyl dose during recovery correlated with maximum pain scores; fentanyl dose was 42% less if ketorolac was administered intraoperatively. In females, the recovery fentanyl dose increased in proportion to the intraoperative fentanyl dose. The maximum pain score was predictive of total recovery time (135, 172, and 212 min of recovery for maximum pain scores of 0-3, 4-6, and 7-10, respectively; P < 0.001). We conclude that improvements in pain therapy are warranted to improve patient comfort and to expedite recovery. IMPLICATIONS: Moderate to severe pain is common after ambulatory surgery and is a frequent cause of delayed discharge. Postoperative pain, opioid-related side effects, and time to discharge were less when nonsteroidal antiinflammatory drugs or local anesthetics were used intraoperatively to prevent pain before patient awakening.

Adult↗

Quality of recovery from anesthesia in neurosurgical patients.

BACKGROUND: Factors influencing quality of recovery in cranial and spinal neurosurgical patients are not known, possibly because of lack of a suitable instrument. Therefore, the authors measured quality of recovery using the QoR-40 score (a 40-item questionnaire on quality of recovery from anesthesia). METHODS: With informed consent, 200 patients undergoing elective neurosurgery were recruited. The QoR-40 score, visual analog scores for pain and quality of recovery, and data on complications were collected over 90 days. The psychometrics of the QoR-40 were tested and regression models were developed to determine predictors of quality of recovery and postoperative pain. RESULTS: The QoR-40 score demonstrated significant responsiveness, validity, and reliability. In cranial surgery patients, QoR-40 scores were lower on days 1 and 2 than either preoperatively or on days 3, 30, and 90. In spinal surgery patients, QoR-40 scores were lower preoperatively and on days 1 and 2 than on days 3, 30, and 90. Longer duration of surgery, more complications, and higher visual analog scores for pain were predictors of poor quality of recovery on day 3. Cranial surgery patients had moderately severe pain on days 1 and 2, whereas spinal surgery patients reported moderate pain for the whole study period. Neurologic deficits were negatively correlated with QoR-40 scores in cranial and spinal surgery patients. CONCLUSIONS: The QoR-40 score is a useful instrument with which to assess quality of recovery in cranial and spinal surgery patients. Postoperative pain and neurologic deficits correlate with poor quality of recovery in these patients.

Adult↗

Predictors of neurologic recovery in acute central cervical cord injury with only upper extremity impairment.

STUDY DESIGN: A prospective study of 22 patients with the syndrome of acute central cervical spinal cord injury with motor and sensory impairment involving only upper extremities (ACCSCI-U) was done from admission to the 2-year follow-up. OBJECTIVES: To evaluate the course of neurologic function and to identify predictors of a good neurologic recovery in patients with ACCSCI-U. SUMMARY OF BACKGROUND DATA: Little is known regarding the time-course profile of neurologic and functional recovery and the prognostic factors for neurologic recovery in patients with ACCSCI-U. METHODS: Between 1997 and 1998, 22 new cases of ACCSCI-U were identified (15 men and 7 women) with a mean age of 45.9 years (range, 13-75 years). They were all treated nonsurgically. Neurologic impairment, as evaluated by the American Spinal Injury Association (ASIA) motor and sensory scores, was assessed on patient arrival at the emergency department and followed prospectively at intervals from admission to the 2-year follow-up. The magnetic resonance imaging (MRI) studies were performed acutely (1 hours to 2 days after injury), subacutely (3-21 days after injury), and chronically (3-9 months after injury). Logistic regression analysis was used to identify the variables that were associated with neurologic improvement. RESULTS: No patient sustained cervical fractures. The mean sagittal diameter of the cervical spinal canals (14.8 mm) was smaller than that of normal subjects in Japan. Of these 22 patients, seven (32%) had radiologic evidence of developmental cervical canal stenosis and two (9%) had evidence of ossification of posterior longitudinal ligament. Thirteen (59%) had cervical spondylosis: of these, four (31%) had cervical stenosis. Nonsurgical treatment resulted in nearly full neurologic recovery within approximately 6 weeks after the injury. None of the patients went on to need surgery. Their average ASIA score of motor, light touch sensation, and pin sensation was increased from 82.2, 104.5, and 104.3 at admission to 99.3, 111.2, and 111.0, respectively, at 2 years after injury. Logistic regression analysis revealed that the best predictor associated with a better neurologic recovery of motor, light touch sensation, and pin sensation was the absence of MRI findings of abnormal signal intensity in the spinal cord, with an odds ratio of 64 (P < 0.006), 13 (P < 0.04),and 15 (P < 0.03), respectively. The results also revealed that percent deficit improvement became significant at 1 week after injury to predict neurologic recovery at 2-year follow-up points. CONCLUSIONS: In patients with ACCSCI-U, a favorable neurologic prognosis can be predicted following nonsurgical treatment. Most recovery occurred by 6 weeks, and patients with severe initial neurologic damage and old age had poorer recovery. Touch and pin sensation recovered at the same rate, whereas motor recovered more quickly. The absence of abnormal MRI signal intensity in the spinal cord and a good early neurologic improvement were the significant predictors of long-term improvement in neurologic function.

Acute Disease↗

Recovery of neurologic function following nontraumatic spinal cord lesions in Israel.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess neurologic recovery and the manner in which it is affected by various factors following nontraumatic spinal cord lesions (NTSCLs). SUMMARY OF BACKGROUND DATA: NTSCLs comprise a considerable portion of spinal cord lesions. However, information about neurologic recovery in these lesions is scarce. METHOD: The study sample included 1,085 patients with NTSCL treated between 1962 and 2000 at the premier referral hospital for rehabilitation in Israel. Demographic and clinical data were collected from hospital charts. The degree of neurologic recovery was determined by comparing each patient's Frankel grades of neurologic deficit at first admission to rehabilitation and at discharge from the same hospitalization. The study population was also compared with previously studied 250 patients with traumatic spinal cord lesions (TSCLs). RESULTS: Complete or substantial neurologic recovery (upgrade to Frankel Grade D or E) occurred during rehabilitation in 51% of patients who were Grade A, B, or C on admission, and in 57% of those who were Grade C. Neurologic recovery in NTSCL during rehabilitation was significantly affected by initial Frankel grade and by NTSCL etiology. Age had a borderline effect. Gender, lesion level, and the decade of rehabilitation did not affect recovery. Recovery rate was usually higher in NTSCLs than in TSCLs. CONCLUSIONS: The prognosis for neurologic recovery is affected mainly by SCL severity and etiology, and is usually better in NTSCLs than in TSCLs.

Adolescent↗

Motor recovery, functional status, and health-related quality of life in patients with complete spinal cord injuries.

STUDY DESIGN: A retrospective cohort with cross- sectional follow-up. OBJECTIVES: The primary objective was to determine motor recovery in patients with complete traumatic spinal cord injury (SCI). Secondary objectives included: 1) determining which factors predict local recovery, 2) assessing functional status using the Functional Independence Measure (FIM), and 3) assessing generic health-related quality of life using the Short Form-36 (SF-36). SUMMARY OF BACKGROUND DATA: Motor recovery following complete SCI has been documented in the literature; however, it has been difficult to interpret: 1) spinal shock is often not addressed; 2) the definition of complete SCI has changed over the last 10 years; and 3) few studies differentiate between local neurologic recovery in the zone of partial preservation and neurologic recovery caudal to the lesion. METHODS: All patients admitted to Vancouver Hospital with a complete SCI between 1994 and 2001 were identified and included in the study if they remained complete following the resolution of spinal shock. Minimum 2-year follow-up consisted of an ASIA motor score, an FIM, and the SF-36. RESULTS: Of 133 patients identified, 94 were eligible and 70 completed follow-up. For the tetraplegic patients, the average ASIA motor score was 11.9 +/- 10.7 on admission and 20.1 +/- 10.8 at follow-up, a change reflecting local recovery only. For the paraplegic patients, the average ASIA motor score was 49.3 +/- 2.4 on admission and 50.6 +/- 1.7 at follow-up. CONCLUSIONS: Motor recovery does not occur below the zone of injury for patients with complete SCI. Varying degrees of local recovery can be expected in tetraplegic individuals.

Adolescent↗

Median and ulnar nerve injuries: a meta-analysis of predictors of motor and sensory recovery after modern microsurgical nerve repair.

BACKGROUND: The aim of this study was to quantify variables that influence outcome after median and ulnar nerve transection injuries. The authors present a meta-analysis based on individual patient data on motor and sensory recovery after microsurgical nerve repair. METHODS: From 130 studies found after literature review, 23 articles were ultimately included, giving individual data for 623 median or ulnar nerve injuries. The variables age, sex, nerve, site of injury, type of repair, use of grafts, delay between injury and repair, follow-up period, and outcome were extracted. Satisfactory motor recovery was defined as British Medical Research Council motor scale grade 4 and 5, and satisfactory sensory recovery was defined as British Medical Research Council grade 3+ and 4. For motor and sensory recovery, complete data were available for 281 and 380 nerve injuries, respectively. RESULTS: Motor and sensory recovery were significantly associated (Spearman r = 0.62, p < 0.001). Multivariate logistic regression analysis showed that age (< 16 years versus > 40 years: odds ratio, 4.3; 95 percent confidence interval, 1.6 to 11.2), site (proximal versus distal: odds ratio, 0.46; 95 percent confidence interval, 0.20 to 1.10), and delay (per month: odds ratio, 0.94; 95 percent confidence interval, 0.90 to 0.98) were significant predictors of successful motor recovery. In ulnar nerve injuries, the chance of motor recovery was 71 percent lower than in median nerve injuries (odds ratio, 0.29; 95 percent confidence interval, 0.15 to 0.55). For sensory recovery, age (odds ratio, 27.0; 95 percent confidence interval, 9.4 to 77.6) and delay (per month: odds ratio, 0.92; 95 percent confidence interval, 0.87 to 0.98) were found to be significant predictors. CONCLUSIONS: In this individual patient data meta-analysis, age, site, injured nerve, and delay significantly influenced prognosis after microsurgical repair of median and ulnar nerve injuries.

Adult↗

Analysis of abnormal recovery pattern of liver function tests after surgical repair of bile duct strictures.

BACKGROUND: Gradual normalization of conventional liver function tests occurs in a majority of patients with extrahepatic biliary obstruction following adequate biliary drainage. Abnormal recovery pattern of liver function has been reported in up to 70% of these patients and there is scarcity of relevant information about this. The purpose of the present paper was to identify variables predictive of abnormal recovery pattern of liver function tests after surgical repair of benign biliary stricture. METHODS: Patient data, disease-related characteristics and serial liver function tests were prospectively collected in 64 patients with post-cholecystectomy bile duct strictures undergoing hepaticojejunostomy. Hepatic histology (fibrosis, portal inflammation, ductular proliferation and cholestasis) was independently graded by two pathologists using a previously validated scale. A cut-off limit of longer than 2 weeks for normalization of liver function tests following definitive surgical repair was considered abnormal. The patients were accordingly dichotomized into groups. Univariate and multivariate analysis was performed. RESULTS: Fourteen patients (22%) each had abnormal recovery pattern of serum bilirubin and serum alanine aminotransferase (ALT) levels while 13 (20%) had abnormal recovery pattern of serum alkaline phosphatase (SAP) levels. Multivariate analysis revealed basal serum bilirubin level was an independent predictor of abnormal recovery pattern of serum bilirubin level while basal ALT level as well as degree of hepatic fibrosis were independent predictors of abnormal recovery of serum ALT level. Similarly, basal SAP level and degree of hepatic fibrosis were independent predictors of abnormal recovery of SAP level. CONCLUSIONS: Basal values of liver function tests and degree of hepatic fibrosis are the most important predictors of abnormal recovery pattern of liver function following adequate biliary decompression in patients with post-cholecystectomy bile duct stricture.

Adolescent↗

The recovery of horses from inhalant anesthesia: a comparison of halothane and isoflurane.

OBJECTIVE: Recovery is one of the more precarious phases of equine general anesthesia. The quality and rate of recovery of horses from halothane and isoflurane anesthesia were compared to determine differences in the characteristics of emergence from these commonly used inhalant anesthetics. EXPERIMENTAL DESIGN: Prospective, randomized blinded clinical trial. SAMPLE POPULATION: A total of 96 Thoroughbred and 3 Standardbred racehorses admitted for elective distal forelimb arthroscopy. METHODS: All horses were premedicated with intravenous xylazine, induced with guaifenesin and ketamine, and maintained on a large animal circle system fitted with an out of the circle, agent specific vaporizer. Recoveries were managed by a blinded scorer with a standardized protocol. A 10 category scoring system was used to assess each horse's overall attitude, purposeful activity, muscle coordination, strength and balance from the time of arrival in recovery to standing. Times to extubation, sternal recumbency and standing were recorded. Median recovery scores and mean times to extubation, sternal and standing were compared using the Mann-Whitney U test and student's t test, respectively. RESULTS: The median score for horses recovering from halothane was lower (20.0; range, 10 to 57) than that for horses recovering from isoflurane (27.5; range, 10 to 55). Horses in the two groups were extubated at similar mean times (halothane, 11.3 +/- 5.5 and isoflurane, 9.5 +/- 5.2 minutes) but horses recovering from isoflurane achieved sternal recumbency (halothane, 37.7 +/- 12.1 and isoflurane, 24.7 +/- 8.8 minutes) and stood (halothane, 40.6 +/- 12.9 and isoflurane, 27.6 +/- 9.6 minutes) sooner than those recovering from halothane. CONCLUSIONS: The recovery of horses from isoflurane anesthesia was more rapid but less composed than that from halothane. CLINICAL RELEVANCE: The quality of recovery following isoflurane was worse than after halothane anesthesia using the criteria chosen for this study. However, the range of recovery scores was similar for both groups and all horses recovered without significant injury.

Anesthesia Recovery Period↗

Measurement of functional recovery in individuals with acute anterior cruciate ligament rupture.

OBJECTIVES: To measure functional recovery following acute anterior cruciate ligament (ACL) rupture using a simple and reliable clinical movement analysis system. Clinic based methods that simultaneously quantify different aspects of movement over a range of activities and model functional recovery will help guide rehabilitation. METHODS: A longitudinal study was used to measure gait variables at initial physiotherapy attendance and then at monthly intervals using a digital camcorder and computer for quantitative analysis. Jogging and distance hopping were added during recovery. A sample of 63 ACL deficient subjects entered the study and 48 subjects were measured at least three times. To determine the pattern of recovery, repeated measurements were analysed using a least square fit of the data. RESULTS: Gait variables took between 95 and 130 days post injury to reach the control mean and stabilise shortly after this. Hopping distance for the injured leg took 62 days to recover to within normal limits and 5 months post injury to reach the control mean. Jogging was already within the control limits at 30 days post injury and demonstrated little change with recovery. CONCLUSIONS: Functional recovery of multiple variables has been modelled. In the early phase of post injury, gait velocity seems to be the most useful variable to measure improvement. Recovery of more challenging activities appears to take an average of 5 months. Therefore, patients may need to be monitored in physiotherapy until this time and advised not to return to sport until sufficient recovery is demonstrated on activities such as distance hopping.

Adult↗

Abnormal heart rate recovery after exercise: a comparison with known indicators of increased mortality.

BACKGROUND: Abnormal heart rate (HR) recovery at 1 min after exercise (< or =12 beats) was recently suggested to be a predictor of all cause and cardiac mortality. AIM: This study aimed to (1) correlate HR recovery at 1 min after exercise with known exercise and myocardial perfusion markers of increased cardiac mortality, and (2) compare the known exercise and myocardial perfusion markers of increased cardiac mortality between patients with a normal and abnormal HR recovery at 1 min after exercise. METHODS: One hundred patients with known or suspected coronary artery disease referred for exercise stress testing (ETT) were prospectively enrolled. Percent, ETT time peak HR, HR reserve, summed stress score (SSS), extent of stress (SE%) and reversible perfusion abnormalities (RE%) were recorded in every patient. RESULTS: There was poor correlation with markers of myocardial ischemia or infarction [SSS (r = 0.15), SE% (r = 0.05), RE% (r = 0.12), all p = n.s.] but highly significant correlation between HR recovery at 1 min after exercise and chronotropic variables [ETT time (r = 0.56), peak HR (r = 0.65), HR reserve % (r = 0.64), all p < 0.001]. Patients on beta-blockers had significantly more incidence of an abnormal HR recovery at 1 min after exercise, compared to patients not on beta-blockers (88 vs. 56%, p < 0.01). CONCLUSION: Abnormal HR recovery at 1 min after exercise has no correlation with known myocardial perfusion markers of increased cardiac mortality. Patients with an abnormal HR recovery do not appear to have an increased incidence or more severe myocardial infarction or ischemia. However, there is a strong correlation between HR recovery at 1 min after exercise and the chronotropic variables during exercise.

Age Factors↗

Delayed blood pressure recovery after psychological stress is associated with carotid intima-media thickness: Whitehall psychobiology study.

OBJECTIVE: Delayed blood pressure (BP) recovery after psychological stress is associated with low socioeconomic status (SES) and prospectively with increases in clinic BP. We tested whether poststress BP recovery was related to carotid atherosclerosis. METHODS AND RESULTS: Psychophysiological stress testing was performed with a healthy subgroup of the Whitehall II epidemiological cohort, and recovery systolic BP was monitored 40 to 45 minutes after stressful behavioral tasks. Carotid ultrasound scanning was conducted on 136 men and women (aged 55.3+/-2.7 years) 3 years after stress testing. Participants were divided into those whose systolic BP had returned to baseline in the recovery period (adequate recovery, n=37), and those whose BP remained elevated (delayed recovery, n=99). Systolic BP stress responses did not differ in the 2 groups. Carotid intima-media thickness (IMT) was associated with delayed recovery in lower SES (means 0.78 versus 0.65 mm) but not higher SES participants (means 0.75 versus 0.74 mm) after adjustment for age, gender, baseline systolic BP, and resting BP, smoking, body mass and fasting cholesterol at the time of ultrasound scanning (P=0.010). CONCLUSIONS: Variations in poststress recovery reflect dysfunction of biological regulatory processes, and may partly mediate psychosocial influences on cardiovascular disease.

Blood Pressure↗

Motor impairment and recovery in the upper limb after stroke: behavioral and neuroanatomical correlates.

BACKGROUND AND PURPOSE: Motor recovery after stroke is associated with cerebral reorganization. However, few studies have investigated the relationship directly, and findings are equivocal. We therefore aimed to characterize the relationship between motor impairment, motor recovery, and task-related changes in regional cerebral blood flow (DeltarCBF) longitudinally. METHODS: We obtained a profile of motor impairment and recovery in the upper limb and conducted positron emission tomography motor activation studies using a simple finger-tapping task in 9 stroke patients 2 to 7 weeks after stroke and 6 months later. For correlation analysis, mean images of task-related DeltarCBF for each individual were linearly regressed with motor impairment scores. Motor recovery was correlated with longitudinal DeltarCBF images. RESULTS: Patients (7 males; 72.0+/-9.8 years) demonstrated a wide range of impairment severity and variable recovery. Upper-limb motor function was linearly correlated with task-related DeltarCBF. Importantly, sites of correlated DeltarCBF differed over time. Subacutely correlated DeltarCBF was observed in supplementary motor area (SMA), bilateral cingulate, and contralesional insula with a small area in ipsilesional primary sensorimotor cortex (SM1). Conversely, at the 6-month study, correlated DeltarCBF was primarily in ipsilesional SM1, extending to the cingulate gyrus. Better motor recovery was correlated with reduction in contralesional activity and increase in ipsilesional SM1. CONCLUSIONS: Upper-limb motor function and recovery are correlated with DeltarCBF in SMA, cingulate, insula, and SM1, highlighting the role of these areas in the recovery process. The dynamic nature of the relationship suggests ongoing adaptation within motor networks.

Aged↗

TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice.

BACKGROUND: Although pharmacological studies suggest that the transient receptor potential vanilloid type 1 (TRPV1) channels expressed in sensory nerve fibers innervating the heart may exert a cardioprotective effect, definitive evidence supporting such a notion is lacking. In addition, function and regulation of sensory neuropeptides, namely, calcitonin gene-related peptide (CGRP) and substance P (SP), in the face of challenges induced by cardiac injury in the presence or absence of the TRPV1 are largely unknown. METHODS AND RESULTS: The hearts of gene-targeted TRPV1-null mutant (TRPV1(-/-)) mice or wild-type (WT) mice were perfused in a Langendorff apparatus in the presence or absence of capsazepine (a TRPV1 receptor antagonist), CGRP, CGRP(8-37) (a CGRP receptor antagonist), SP, or RP67580 (a neurokinin-1 [NK1] receptor antagonist) when hearts were subjected to 40 minutes of ischemia and 30 minutes of reperfusion. Hemodynamic alterations and SP release measured by radioimmunoassay were assessed before and after ischemia/reperfusion injury of the heart. Expression of the NK1 receptor in the hearts of TRPV1(-/-) and WT mice were determined with the use of Western blot analyses. Impairment of postischemic recovery, defined by increased left ventricular end-diastolic pressure (LVEDP) and decreased left ventricular developed pressure (LVDP) and coronary flow (CF), was more severe in TRPV1(-/-) hearts than in WT hearts. Although it had no effect on postischemic recovery of TRPV1(-/-) hearts, blockade of the TRPV1 with capsazepine caused a most severe impairment of postischemic recovery in WT hearts compared with untreated WT and TRPV1(-/-) hearts. Exogenous CGRP and SP produced a significant improvement in postischemic recovery in both TRPV1(-/-) and WT hearts, and the maximal functional improvement in TRPV1(-/-) hearts was not different from that of WT hearts except that SP-induced increases in LVDP were larger in the former than in the latter. Blockade of the NK1 receptor with RP67580, but not blockade of the CGRP receptor with CGRP(8-37), caused more severe impairment in postischemic recovery in both TRPV1(-/-) and WT hearts than in untreated hearts in both genotypes. The release of SP after ischemia/reperfusion injury was increased in both WT and TRPV1(-/-) hearts, albeit with a smaller magnitude of the increase in the latter. Capsazepine attenuated injury-induced SP release in WT but not TRPV1(-/-) hearts. There was no difference in the expression of the NK1 receptor between the 2 genotype hearts. CONCLUSIONS: Thus, our data show that (1) TRPV1 gene deletion decreases injury-induced SP release and impairs cardiac recovery function after ischemia/reperfusion injury; (2) TRPV1 gene deletion leads to reconditioning of the heart with improved postischemic recovery compared with that induced by acute TRPV1 blockade and in terms of cardiac response to exogenous SP; and (3) blockade of the NK1 but not CGRP receptors worsens postischemic recovery of hearts in both genotypes. Taken together, these data indicate that TRPV1 plays a role in protecting the heart from injury possibly via increasing SP release and that deletion of this receptor reconditions the heart for escaping, at least in part, from injury possibly via enhancing NK1 receptor function.

Animals↗

A new method for predicting recovery after stroke.

BACKGROUND AND PURPOSE: Several prognostic factors have been identified for outcome after stroke. However, there is a need for empirically derived models that can predict outcome and assist in medical management during rehabilitation. To be useful, these models should take into account early changes in recovery and individual patient characteristics. We present such a model and demonstrate its clinical utility. METHODS: Data on functional recovery (Barthel Index) at 0, 2, 4, 6, and 12 months after stroke were collected prospectively for 299 stroke patients at 2 London hospitals. Multilevel models were used to model recovery trajectories, allowing for day-to-day and between-patient variation. The predictive performance of the model was validated with an independent cohort of 710 stroke patients. RESULTS: Urinary incontinence, sex, prestroke disability, and dysarthria affected the level of outcome after stroke; age, dysphasia, and limb deficit also affected the rate of recovery. Applying this to the validation cohort, the average difference between predicted and observed Barthel Index was -0.4, with 90% limits of agreement from -7 to 6. Predicted Barthel Index lay within 3 points of the observed Barthel Index on 49% of occasions and improved to 69% when patients' recovery histories were taken into account. CONCLUSIONS: The model predicts recovery at various stages of rehabilitation in ways that could improve clinical decision making. Predictions can be altered in light of observed recovery. This model is a potentially useful tool for comparing individual patients with average recovery trajectories. Patients at elevated risk could be identified and interventions initiated.

Activities of Daily Living↗