Major Bleeding Postadministration of Tenecteplase Versus Alteplase in Acute Ischemic Stroke.

BACKGROUND: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. OBJECTIVE: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. METHODS: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. RESULTS: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. CONCLUSIONS AND RELEVANCE: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

Self-reported long-term needs after stroke.

BACKGROUND AND PURPOSE: Development of interventions to manage patients with stroke after discharge from the hospital requires estimates of need. This study estimates the prevalence of self-reported need in community-dwelling stroke survivors across the United Kingdom. METHODS: We conducted a survey of stroke survivors 1 to 5 years poststroke recruited through Medical Research Council General Practice Research Framework general practices and 2 population-based stroke registers. Levels and type of need were calculated with comparisons among sociodemographic groups, disability level, and cognitive status using the χ2 test or Fisher exact test, as appropriate. RESULTS: From 1251 participants, response rates were 60% (national sample) and 78% (population registers sample) with few differences in levels of reported need between the 2 samples. Over half (51%) reported no unmet needs; among the remainder, the median number of unmet needs was 3 (range, 1 to 13). Proportions reporting unmet clinical needs ranged from 15% to 59%; 54% reported an unmet need for stroke information; 52% reported reduction in or loss of work activities, significantly more from black ethnic groups (P=0.006); 18% reported a loss in income and 31% an increase in expenses with differences by age, ethnic group, and deprivation score. In multivariable analysis, ethnicity (P=0.032) and disability (P=0.014) were associated with total number of unmet needs. CONCLUSIONS: Multiple long-term clinical and social needs remain unmet long after incident stroke. Higher levels of unmet need were reported by people with disabilities, from ethnic minority groups, and from those living in the most deprived areas. Development and testing of novel methods to meet unmet needs are required.

Signal intensity in T2' magnetic resonance imaging is related to brain glioma grade.

OBJECTIVES: T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas. METHODS: MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis. RESULTS: Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p < 0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875). CONCLUSIONS: High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism.

Platelet-leucocyte adhesion markers before and after the initiation of antiretroviral therapy with HIV protease inhibitors.

INTRODUCTION: Thromboembolic complications under antiretroviral therapy (ART) have been described in the past. In particular, the influence of protease inhibitors (PIs) on platelet activation and coagulation is currently under discussion. METHODS: HIV-1-infected, PI-naive adults (n = 18) were investigated before and 4 weeks after the start of the ART, consisting either of boosted PI regimens (n = 13) plus reverse transcriptase inhibitors (RTIs) or a double PI regimen (n = 5) without RTI co-medication. Administered PIs were saquinavir (n = 15), lopinavir (n = 4), fosamprenavir (n = 2) and atazanavir (n = 2). Platelet CD62P, CD40L (%+ cells) and PAC-1 binding [mean fluorescence intensity (MFI)] as well as monocyte CD11b (MFI) and monocyte-associated CD41 (%+ cells and MFI) expression were assessed by flow cytometry with or without platelet stimulation. To investigate the influence of platelets on coagulation, the endogenous thrombin potential (ETP) [render fluorescence units (RFI)] was determined. RESULTS: CD62P, PAC-1 binding and CD11b expression remained unchanged. In contrast, the mean+/-SD MFI of CD40L (from 18.2+/-9.0 to 25.5+/-10.4, P = 0.038) and CD41 (from 446.1+/-213.8 to 605.0+/-183.8, P = 0.010) as markers for increased platelet-leucocyte interaction increased significantly. The collagen-induced ETP time-to-peak was altered significantly from 23.8+/-11.4 to 17.0+/-4.2 min (P = 0.028), although the ETP RFI peak showed no evidence for increased procoagulatory capacity (47.1+/-18.6 to 57.3+/-19.9, P = 0.085). CONCLUSIONS: Effects of the evaluated PI HIV therapy on platelet function assessed under field conditions seem to be minor, not affecting all investigated parameters. We found no evidence for increased platelet activation under PI-containing ART. However, CD41 as a marker for increased platelet-leucocyte interaction and CD40L, which can contribute to atherosclerosis, increased significantly.

Improvement of tactile discrimination performance and enlargement of cortical somatosensory maps after 5 Hz rTMS.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used to investigate mechanisms of brain functions and plasticity, but also as a promising new therapeutic tool. The effects of rTMS depend on the intensity and frequency of stimulation and consist of changes of cortical excitability, which often persists several minutes after termination of rTMS. While these findings imply that cortical processing can be altered by applying current pulses from outside the brain, little is known about how rTMS persistently affects learning and perception. Here we demonstrate in humans, through a combination of psychophysical assessment of two-point discrimination thresholds and functional magnetic resonance imaging (fMRI), that brief periods of 5 Hz rTMS evoke lasting perceptual and cortical changes. rTMS was applied over the cortical representation of the right index finger of primary somatosensory cortex, resulting in a lowering of discrimination thresholds of the right index finger. fMRI revealed an enlargement of the right index finger representation in primary somatosensory cortex that was linearly correlated with the individual rTMS-induced perceptual improvement indicative of a close link between cortical and perceptual changes. The results demonstrate that repetitive, unattended stimulation from outside the brain, combined with a lack of behavioral information, are effective in driving persistent improvement of the perception of touch. The underlying properties and processes that allow cortical networks, after being modified through TMS pulses, to reach new organized stable states that mediate better performance remain to be clarified.

Clinical applications of quantitative T2 determination: a complementary MRI tool for routine diagnosis of suspected myelination disorders.

BACKGROUND AND AIMS: Though magnetic resonance imaging (MRI) plays an important role in studying pathological changes in central nervous system, a quantitative measure of contrast variance on MRI, allowing the detection of subtle signal variances in pathological processes, is not readily available for routine imaging. We report on the first experiences with evaluation of routine T2 relaxation time measurement as a diagnostic tool in routine imaging of suspected myelination disorders. METHODS: Twenty patients suffering from defined or suspected myelination disorders were examined by MRI. T2 relaxation time maps of the brain were derived from a triple spin echo sequence. T2 values were measured for each patient by regions of interest (ROI) analysis. As references age-dependent T2 prediction values in normal maturating brains were calculated by using a biexponentional function reported earlier. Deviations from these prediction values were used as an assisting tool both for detection of pathology and for monitoring of changes over time. These quantitative results were compared to conventional visual inspections by two independent neuroradiologists. RESULTS: In 18 patients with single diagnostic MRI, the T2 measurements were more graduated or definite in 9/18 cases, confirmatory in 9/18 cases. In two patients with MRI follow up, the dynamic clinical course of the disease had no correlate in visual inspection of the images but was associated with the quantitative T2 values. CONCLUSIONS: Quantitative T2 measurement is a promising tool for routine imaging as a complementary method in detecting and monitoring of suspected myelination disorders.

Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.

In the complex regional pain syndrome (CRPS), several theories proposed the existence of pathophysiological mechanisms of central origin. Recent studies highlighted a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) during non-painful stimulation of the affected side. We addressed the question whether reorganizational changes can also be found in the secondary somatosensory cortex (SII). Moreover, we investigated whether cortical changes might be accompanied by perceptual changes within associated skin territories. Seventeen patients with CRPS of one upper limb without the presence of peripheral nerve injuries (type I) were subjected to functional magnetic resonance imaging (fMRI) during electrical stimulation of both index fingers (IFs) in order to assess hemodynamic signals of the IF representation in SI and SII. As a marker of tactile perception, we tested 2-point discrimination thresholds on the tip of both IFs. Cortical signals within SI and SII were significantly reduced contralateral to the CRPS-affected IF as compared to the ipsilateral side and to the representation of age- and sex-matched healthy controls. In parallel, discrimination thresholds of the CRPS-affected IF were significantly higher, giving rise to an impairment of tactile perception within the corresponding skin territory. Mean sustained, but not current pain levels were correlated with the amount of sensory impairment and the reduction in signal strength. We conclude that patterns of cortical reorganization in SI and SII seem to parallel impaired tactile discrimination. Furthermore, the amount of reorganization and tactile impairment appeared to be linked to characteristics of CRPS pain.

Sensorimotor retuning [corrected] in complex regional pain syndrome parallels pain reduction.

Patients with complex regional pain syndrome (CRPS) and intractable pain showed a shrinkage of cortical maps on primary (SI) and secondary somatosensory cortex (SII) contralateral to the affected limb. This was paralleled by an impairment of the two-point discrimination thresholds. Behavioral treatment over 1 to 6 months consisting of graded sensorimotor retuning led to a persistent decrease in pain intensity, which was accompanied by a restoration of the impaired tactile discrimination and regaining of cortical map size in contralateral SI and SII. This suggests that the reversal of tactile impairment and cortical reorganization in CRPS is associated with a decrease in pain.

Crossed cerebro-cerebellar language dominance.

In addition to its traditional role in motor control, the cerebellum has been implicated in various cognitive and linguistic functions. Lesion, anatomic, and functional imaging studies indicate a link between left frontal language regions and the right cerebellum. To probe the specificity of this circuit, we examined the association between language-related lateralized activation of the frontal cortex with lateralized activation of the cerebellum. Functional magnetic resonance imaging (fMRI) was carried out during letter-cued word generation in 14 healthy subjects: 7 subjects displayed typical left-hemisphere and 7 subjects displayed atypical right-hemisphere language dominance. We found activation of the cerebellar hemisphere contralateral to the language-dominant cerebral hemisphere in each subject. The cerebellar activation was confined to the lateral posterior cerebellar hemisphere (lobule VI, VII B, Cr I, Cr II). This study demonstrates that crossed cerebral and cerebellar language dominance is a typical characteristic of brain organization. The functional significance of the reported activations can now be tested in patients with lesions of the lateral posterior cerebellum.