Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials.

BACKGROUND: Since its approval, the use of alteplase had been limited to patients aged ≤80 years. AIMS: TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence. METHODS: TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0-2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly. RESULTS: Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69-2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights. CONCLUSIONS: The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.

Effects of Palmitoylethanolamide Combined with Luteoline on Frontal Lobe Functions, High Frequency Oscillations, and GABAergic Transmission in Patients with Frontotemporal Dementia.

BACKGROUND: Frontotemporal dementia (FTD) is a presenile neurodegenerative disease for which there is no effective pharmacological treatment. Recently, a link has been proposed between neuroinflammation and FTD. OBJECTIVE: Here, we aim to investigate the effects of palmitoylethanolamide (PEA) combined with luteoline (PEA-LUT), an endocannabinoid with anti-inflammatory and neuroprotective effects, on behavior, cognition, and cortical activity in a sample of FTD patients. METHODS: Seventeen patients with a diagnosis of probable FTD were enrolled. Cognitive and neurophysiological evaluations were performed at baseline and after 4 weeks of PEA-LUT 700 mg×2/day. Cognitive effects were assessed by Neuropsychiatric Inventory (NPI), Mini-Mental State Examination, Frontal Assessment Battery (FAB), Screening for Aphasia in Neurodegeneration, Activities of Daily Living-Instrumental Activities of Daily Living, and Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating scale. To investigate in vivo neurophysiological effects of PEA-LUT, we used repetitive and paired-pulse transcranial magnetic stimulation (TMS) protocols assessing LTP-like cortical plasticity, short-interval intracortical inhibition, long-interval intracortical inhibition (LICI), and short-latency afferent inhibition. Moreover, we used TMS combined with EEG to evaluate the effects on frontal lobe cortical oscillatory activity. RESULTS: Treatment with PEA-LUT was associated with an improvement in NPI and FAB scores. Neurophysiological evaluation showed a restoration of LICI, in particular at ISI 100 ms, suggesting a modulation of GABA(B) activity. TMS-EEG showed a remarkable increase of TMS-evoked frontal lobe activity and of high-frequency oscillations in the beta/gamma range. CONCLUSION: PEA-LUT could reduce behavioral disturbances and improve frontal lobe functions in FTD patients through the modulation of cortical oscillatory activity and GABA(B)ergic transmission.

Clinical worsening despite intravenous thrombolysis in acute ischemic stroke secondary to carotid plaque rupture.

First-line therapy of acute ischemic stroke is intravenous thrombolysis (IVT) irrespective of etiology. We report on a patient with acute ischemic stroke secondary to carotid plaque rupture who experienced plaque thrombosis and marked clinical worsening despite IVT. While the latter is the gold standard therapy optimal platelets inhibition should be guaranteed to allow a safe as possible carotid intervention. Hereby we discuss all available strategies to be considered in order to better individualized treatment decision-making.

Efficacy and Safety of Mechanical Thrombectomy in Older Adults with Acute Ischemic Stoke.

OBJECTIVES: To evaluate the safety and efficacy of endovascular therapy in elderly adults treated for acute ischemic stroke. DESIGN: Retrospective cohort study. SETTING: Comprehensive Stroke Center, University of Tor Vergata, Rome, Italy. PARTICIPANTS: Elderly adults treated for acute ischemic stroke (N = 219). MEASUREMENTS: Participants were divided into two groups based on their age (n = 62, ≥80; n = 157, <80). Baseline and procedural characteristics, safety outcomes such as intracranial hemorrhage (ICH) and mortality and efficacy outcomes such as successful reperfusion and 3-month good clinical outcome of the two groups were compared. Mutivariable analysis was performed to identify predictors of clinical outcome. RESULTS: Intravenous thrombolysis was more frequent (67.7% vs 52.8%, P = .04), and onset to reperfusion time was shorter (318.7 ± 128.7 vs 282 ± 53.5, P = .02) in participants aged 80 and older, but no between-group differences were found in terms of successful reperfusion (69% vs 63%, P = .4), good clinical outcome (30.6% vs 34.3%, P = .6), any (37% vs 37.5%, P > .99) or symptomatic (11% vs 14%, P = .6) ICH, or mortality (40.3% vs 29.2%, P = .14). Multivariable analysis revealed that, in the older group, onset National Institute of Health Stroke Scale (NIHSS) score (odds ratio (OR) = 0.65, 95% confidence interval (CI) = 0.44-0.96, P = .03) and 24-hour clinical improvement (OR = 141.13, 95% CI = 2.96-6,720.7, P = .01) were independent predictors of 3-month functional independence. CONCLUSION: These findings suggest that endovascular treatment for stroke in selected elderly adults could be safe and effective. Major determinants of outcome in this subgroup of elderly patients are presentation NIHSS score and 24-hour clinical improvement.

CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke.

BACKGROUND: Collateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy. METHODS: Baseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals. RESULTS: Evaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0-2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome. CONCLUSIONS: CTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.

Intra-arterial thrombectomy versus standard intravenous thrombolysis in patients with anterior circulation stroke caused by intracranial arterial occlusions: a single-center experience.

BACKGROUND: Severely impaired patients with persisting intracranial occlusion despite standard treatment with intravenous (IV) administration of recombinant tissue plasminogen activator (rtPA) or presenting beyond the therapeutic window for IV rtPA may be candidates for interventional neurothrombectomy (NT). The safety and efficacy of NT by the Penumbra System (PS) were compared with standard IV rtPA treatment in patients with severe acute ischemic stroke (AIS) caused by large intracranial vessel occlusion in the anterior circulation. METHODS: Consecutive AIS patients underwent a predefined treatment algorithm based on arrival time, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score, and site of arterial occlusion on computed tomographic angiography (CTA). NT was performed either after a standard dose of IV rtPA (bridging therapy [BT]) or as single treatment (stand-alone NT [SAT]). Rates of recanalization, symptomatic intracranial bleeding (SIB), mortality, and functional outcome in NT patients were compared with a historical cohort of IV rtPA treated patients (i.e., controls). Three-month favourable outcome was defined as a modified Rankin Scale (mRS) score ≤2. RESULTS: Forty-six AIS patients were treated with NT and 51 with IV rtPA. The 2 groups did not differ with regard to demographics, onset NIHSS score (18.5±4 v 17±5; P=.06), or site of intracranial occlusion. Onset-to-treatment time in the NT and IV rtPA groups was 230 minutes (±78) and 176.5 (±44) minutes, respectively (P=.001). NT patients had significantly higher percentages of major improvement (≥8 points NIHSS score change at 24 hours; 26% v 10%; P=.03) and partial/complete recanalization (93.5% v 45%; P<.0001) compared to controls. Treatment by either SAT or BT similarly improved the chance of early recanalization and early clinical improvement. No significant differences were observed in the rate of SIB (11% v 6%), 3-month mortality (24% v 25%), or favorable outcome (40% v 35%) between NT and IV rtPA patients. CONCLUSIONS: Despite significantly delayed time of intervention, NT patients had higher rates of recanalization and early major improvement, with no differences in symptomatic intracranial hemorrhages. Early NIHSS score improvement did not translate into better 3-month mortality or outcome. NT seems a safe and effective adjuvant treatment strategy for selected patients with severe AIS secondary to large intracranial vessel occlusion in the anterior circulation.

Long-term consequences of pelvic trauma patients with thromboembolic disease treated with inferior vena caval filters.

BACKGROUND: The use of inferior vena cava (IVC) filters for prevention of pulmonary embolism (PE) in high-risk trauma patients is well accepted. High rates of recurrent venous thrombosis, however, and postthrombotic syndrome (PTS) have been reported in nonsurgical patients with medical comorbidities. Patients with pelvic trauma and thromboembolic disease have a unique thrombogenic pathophysiology, and the long-term consequences of filter placement in these patients are unknown. We sought to evaluate the outcomes of patients who sustained pelvic trauma, and who developed venous thrombosis and were treated with a vena caval filter. METHODS: A cohort of 102 consecutive patients was treated for a pelvic or acetabular fracture who developed deep vein thrombosis (DVT) preoperatively and had a caval filter placed. Thromboembolic events and complications were evaluated by both retrospective chart review and a prospective questionnaire. Eighty-eight patients (86%) returned the questionnaire at an average follow-up of 4 years. RESULTS: No patients were readmitted to the hospital for recurrent venous thrombosis or PE. Six patients (7%) described new swelling in the lower extremities, and one (1%) demonstrated evidence of PTS. No deaths occurred related to PE. CONCLUSIONS: The use of IVC filters appears to be safe and effective in preventing PE in patients with pelvic trauma and established venous thrombosis. The risk of recurrent DVT is low and PTS is negligible in these patients. Filter placement use is not associated with the same long-term complications as in patients with thrombosis because of chronic medical comorbidities.

Management of persistent postpartum pelvic pain.

Persistent postpartum pelvic pain is an uncommon but disabling disorder. Although symptoms resolve spontaneously in the majority of cases, some carefully selected women with this chronic condition might benefit from surgical stabilization of the pelvic ring. We retrospectively studied 19 patients whose persistent postpartum pelvic pain was treated at our center. Although most patients were successfully treated nonoperatively, 6 (31.5%) underwent surgery because of symptoms persisting more than 1 year. Imaging studies, including magnetic resonance imaging, were used to assess the extent and the nature of the lesion before surgery. Eleven patients had degenerative changes in the anterior pelvic ring; the other 8 patients had degenerative sacroiliac joint changes. Surgical procedures included resection of the diseased fragment, anterior symphyseal plating, and bone grafting with and without posterior ring stabilization. For all patients, mean Majeed outcome score was 85 (range, 46-100). No significant difference in outcomes was found between the surgically treated patients and the nonoperatively treated patients.

Plate fixation of ununited humeral shaft fractures: effect of type of bone graft on healing.

BACKGROUND: Delayed union or nonunion of a fracture of the humerus is an infrequent but debilitating complication. Open reduction and internal fixation combined with autologous bone-grafting can result in reliable healing of the fracture; however, there is morbidity associated with the bone-graft donor site. This study was designed to evaluate healing of ununited fractures of the humeral shaft treated by one surgeon at one institution with a strict and consistent surgical protocol but with the use of two different types of bone graft: autologous iliac crest bone graft and demineralized bone matrix. METHODS: A consecutive retrospective cohort series was analyzed. From 1992 to 1999, forty-five patients with an aseptic, atrophic delayed union or nonunion of a humeral shaft fracture were treated with open reduction and internal fixation with a plate and autologous iliac crest bone graft. The mean time from the fracture to the surgery was 14.0 months, and the mean duration of follow-up was 32.8 months. From 2000 to 2003, thirty-three patients with the same condition were treated with the same protocol with the exception that demineralized bone matrix was used instead of autologous iliac crest bone graft. The mean time from the fracture to the surgery in that group was 22.6 months, and the mean duration of follow-up was 20.4 months. All patients in both groups were assessed clinically and radiographically. RESULTS: Osseous union was noted clinically and radiographically following the index surgery in 100% of the forty-five patients treated with autologous bone graft and 97% (thirty-two) of the thirty-three patients treated with demineralized bone matrix. The mean time to union was 4.5 months in the group treated with autologous bone graft and 4.2 months in the group treated with demineralized bone matrix. The overall functional outcome did not differ between the groups; however, twenty (44%) of the autologous bone-graft recipients had donor site morbidity, including a prolonged pain in the majority and a superficial infection requiring irrigation and débridement in one patient. CONCLUSIONS: Healing of an ununited humeral shaft fracture can be achieved consistently with rigid plate fixation and lag-screw compression augmented with either autologous cancellous bone graft or commercially available demineralized bone matrix. The harvest of the autologous bone graft is frequently associated with complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.