Second-dose intravenous thrombolysis with tenecteplase in alteplase-resistant medium-vessel-occlusion strokes: A retrospective and comparative study.

INTRODUCTION: In intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase. PATIENTS AND METHODS: This retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup. RESULTS: Among 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p < 0.0001), with similar sICH rate (3 vs 2, p = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p < 0.0001). Propensity score matching analyses supported all these associations. CONCLUSION: In this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05809921.

Detection of moderate to severe middle cerebral artery atherosclerotic stenosis in stroke patients: Transcranial color-coded duplex sonography versus computed tomography angiography.

Background: Intracranial atherosclerotic stenosis is a common cause of ischemic cerebrovascular events and is associated with a high risk of stroke recurrence. This study aimed to assess the diagnostic accuracy of transcranial color-coded duplex sonography for moderate-to-severe middle cerebral artery stenosis in stroke patients. Methods: A retrospective analysis was carried out, including 31 patients aged ⩾18 years hospitalized for ischemic cerebrovascular event in whom middle cerebral artery stenosis ⩾30% was identified on computed tomography angiography. Transcranial color-coded duplex sonography findings were compared to the degree of stenosis blindly identified on the computed tomography angiography used as the reference method. Results: Overall, 27 patients had M1 stenosis and the other 4 had M2 stenosis. To detect M2 stenosis ⩾ 50% and ⩾ 70%, stenotic to pre-stenotic ratio ⩾ 2 and ⩾ 3 had a sensitivity of 100%, respectively. To detect M1 stenosis ⩾ 70%, peak systolic velocity ⩾ 300 cm/s had a sensitivity of 53.8% and specificity of 85.7% with area under the receiver-operating characteristic curve of 0.753 (95% confidence interval: 0.568-0.938; p = 0.026), and stenotic to pre-stenotic ratio ⩾ 3 had a sensitivity of 84.6% and a specificity of 78.6% (area under the curve = 0.854; 95% confidence interval: 0.707-1; p = 0.002). Middle cerebral artery/anterior cerebral artery velocity ratio < 0.7 had a sensitivity of 57.1% and specificity of 90% to detect dampened pre-stenotic flow in middle cerebral artery secondary to downstream M1 stenosis ⩾ 70% (area under the curve = 0.800; 95% confidence interval: 0.584-1; p = 0.040). Conclusion: This study showed that stenotic to pre-stenotic ratio ⩾ 3 was more sensitive than peak systolic velocity ⩾ 300 cm/s to screen M1 stenosis ⩾ 70%. Middle cerebral artery/anterior cerebral artery ratio < 0.7 was a good indirect sign to detect dampened pre-stenotic flow due to M1 stenosis ⩾ 70%.

Functional Outcome, Recanalization, and Hemorrhage Rates After Large Vessel Occlusion Stroke Treated With Tenecteplase Before Thrombectomy.

BACKGROUND AND OBJECTIVES: To investigate in routine care the efficacy and safety of IV thrombolysis (IVT) with tenecteplase prior to mechanical thrombectomy (MT) in patients with large vessel occlusion acute ischemic strokes (LVO-AIS), either secondarily transferred after IVT or directly admitted to a comprehensive stroke center (CSC). METHODS: We retrospectively analyzed clinical and procedural data of patients treated with 0.25 mg/kg tenecteplase within 270 minutes of LVO-AIS who underwent brain angiography. The main outcome was 3-month functional independence (modified Rankin Scale score ≤2). Recanalization (revised Treatment in Cerebral Ischemia score 2b-3) was evaluated before (pre-MT) and after MT (final). RESULTS: We included 588 patients (median age 75 years [interquartile range (IQR) 61-84]; 315 women [54%]; median NIH Stroke Scale score 16 [IQR 10-20]), of whom 520 (88%) were secondarily transferred after IVT. Functional independence occurred in 47% (n = 269/570; 95% confidence interval [CI] 43.0-51.4) of patients. Pre-MT recanalization occurred in 120 patients (20.4%; 95% CI 17.2-23.9), at a similar rate across treatment paradigms (direct admission, n = 14/68 [20.6%]; secondary transfer, n = 106/520 [20.4%]; p > 0.99) despite a shorter median IVT to puncture time in directly admitted patients (38 [IQR 23-55] vs 86 [IQR 70-110] minutes; p < 0.001). Final recanalization was achieved in 492 patients (83.7%; 95%CI 80.4-86.6). Symptomatic intracerebral hemorrhage occurred in 2.5% of patients (n = 14/567; 95% CI 1.4-4.1). DISCUSSIONS: Tenecteplase before MT is safe, effective, and achieves a fast recanalization in everyday practice in patients secondarily transferred or directly admitted to a CSC, in line with published results. These findings should encourage its wider use in bridging therapy. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that tenecteplase within 270 minutes of LVO-AIS increases the probability of functional independence.

Isolated cerebellar nodulus infarction: Two case reports and literature review.

BACKGROUND: Isolated cerebellar nodulus infarction (ICNI) is rare and has great clinical similarity with acute peripheral vestibulopathy (APV), from which it is difficult to distinguish. We report two cases of ICNI followed by a literature review to identify the discriminant clinical elements that differentiate ICNI from APV. METHODS: We describe in detail our 2 cases. Besides, a literature search in Medline via PubMed and Scopus was performed up to May 17, 2020. Clinical characteristics, mainly of well-described cases, were extracted and analyzed. RESULTS: Our search yielded 43 total publications, among which 13 were selected, including 23 patients. Spontaneous or positional rotatory vertigo with unidirectional spontaneous horizontal nystagmus, associated with the postural imbalance and unilateral lateropulsion or fall on Romberg's test, was the most common clinical picture. According to our literature review, the discriminant clinical elements which differentiate ICNI from APV were direction-changing gaze-evoked nystagmus, bilateral lateropulsion or fall on Romberg's test, and normal horizontal head impulse test. Our two patients reported a positional fleeting abnormal visual perception of spatial orientation of objects. We proposed this symptom as a discriminant clinical element. CONCLUSION: The ICNI constitutes a difficult differential diagnosis of APV. Through our two patients reported here, we proposed a supplementary discriminant symptom helpful for the clinical diagnosis.

Reversal of Vitamin K Antagonist Therapy Before Thrombolysis for Acute Ischemic Stroke.

Background and Purpose- Acute ischemic strokes under vitamin K antagonist (VKA) treatment are not uncommon, but intravenous thrombolysis (IVT) is not recommended for international normalized ratio (INR) >1.7 because of the excess bleeding risk. However, VKA-induced anticoagulation can be easily reversed by IV infusions of 4-factor prothrombin complex concentrate bolus and vitamin K. Our pilot study aimed to determine whether IVT immediately after anticoagulation reversal could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Methods- Consecutive acute ischemic stroke patients, otherwise eligible for IVT except for VKA intake and INR >1.7, were given IVT after infusing 4-factor prothrombin complex concentrate and vitamin K. Safety and efficacy were assessed clinically and by cerebral imaging at 24 hours. Results- Twenty-six patients (age, 77.8±12.8 years; atrial fibrillation, 84.6%; initial National Institutes of Health Stroke Scale, 11.6±5.6) were prospectively included. INR values were 2.3±0.6 initially and 1.3±0.2, 5 minutes postreversal. No symptomatic intracranial hemorrhage or thrombotic events occurred during the first 3 days. One patient developed major systemic hemorrhoidal bleeding that required blood transfusion; 61.5% of the patients were independent (modified Rankin Scale score of ≤2) at 3 months. Conclusions- A reversal strategy of 4-factor prothrombin complex concentrate bolus and vitamin K before IVT could be feasible and safe in acute ischemic stroke patients under VKA with INR >1.7. Well-designed, randomized controlled trials are warranted to confirm these preliminary findings.

Impact of protein energy wasting status on survival among Afro-Caribbean hemodialysis patients: a 3-year prospective study.

BACKGROUND: We assessed the prognostic value of protein-energy wasting (PEW) on mortality in Afro-Caribbean MHD patients and analysed how diabetes, cardiovascular disease (CVD) and inflammation modified the predictive power of a severe wasting state. METHOD: A 3-year prospective study was conducted in 216 patients from December 2011. We used four criteria from the nomenclature for PEW proposed by the International Society of Renal Nutrition and Metabolism in 2008: serum albumin 38 g/L, body mass index (BMI) ≤23 kg/m(2), serum creatinine ≤818 µmol/L and protein intake assessed by nPCR ≤0.8 g/kg/day. PEW status was categorized according the number of criteria. Cox regression analyses were used. RESULTS: Forty deaths (18.5 %) occurred, 97.5 % with a CV cause. Deaths were distributed as follows: 7.4 % in normal nutritional status, 13.2 % in slight wasting (1 PEW criterion), 28 % in moderate wasting (2 criteria) and 50 % in severe wasting (3-4 criteria). Among the PEW markers, low serum albumin (HR 3.18; P = 0.001) and low BMI (HR 1.97; P = 0.034) were the most significant predictors of death. Among the PEW status categories, moderate wasting (HR 3.43; P = 0.021) and severe wasting (HR 6.59; P = 0.001) were significant predictors of death. Diabetes, CVD, and inflammation were all additives in predicting death in association with severe wasting with a strongest HR (7.76; P < 0.001) for diabetic patients. CONCLUSIONS: The nomenclature for PEW predicts mortality in our Afro-Caribbean MHD patients and help to identify patients at risk of severe wasting to provide adequate nutritional support.

Clinical varieties and epidemiological aspects of amyotrophic lateral sclerosis in the Caribbean island of Guadeloupe: A new focus of ALS associated with Parkinsonism.

Our objective was to evaluate the epidemiological and clinical characteristics of amyotrophic lateral sclerosis (ALS) in the Caribbean island of Guadeloupe, using a retrospective study covering 15 years (1996-2011). Sixty-three cases of ALS were reported, with a frequency of 0.93/100,000/year. The incidence was 4.5-fold higher (3.73/100,00/year) on Marie-Galante, a small island in the Guadeloupe archipelago. ALS was associated with Parkinsonism in 23.8% of the cases. Other phenotypes were typical ALS (47.6%), bulbar forms (20.6%), limb-onset variants (6.3%) and ALS associated with frontotemporal dementia (1.6%). Onset of ALS-Parkinsonism was significantly later than in typical forms of ALS (68 vs. 54 years; p = 0.012) and affected males more frequently than did bulbar ALS (80% vs. 23.2%; p = 0.003). After one year of disease duration, the clinical profile of ALS-Parkinsonism included a symmetric akineto-rigid Parkinsonian syndrome unresponsive to levodopa, supranuclear oculomotor palsy (50%), dementia (66.7%) and signs of both lower (100%) and upper (86%) motor neuron involvement, including bulbar signs (100%). In conclusion, a new cluster of ALS-Parkinsonism and a geographical area with a high frequency of ALS were identified in Guadeloupe, suggesting that they result from environmental or genetic factors. Further studies are needed to explore these hypotheses.

Factors influencing prognosis and functional outcome one year after a first-time stroke in a Caribbean population.

OBJECTIVE: To evaluate functional outcome and quality of life 1 year poststroke in a Caribbean population. DESIGN: Prospective study of patients with a first hemispheric stroke admitted consecutively between December 2010 and February 2011. The patients were evaluated (1) in the emergency department, (2) when discharged from the hospital, and (3) 1 year poststroke. SETTING: A university hospital. PARTICIPANTS: Of the 140 consecutive patients with stroke, 78 (42% women, 24.4% hemorrhagic stroke) were included in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), FIM, and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: The mean age of the participants was 62.1±17.7 years; 70.5% of patients had hypertension, 29.4% had diabetes, and 23.6% had chronic renal failure. At 1 year poststroke, the mortality rate was 29.4%, and the recurrence rate 2.6%. We evaluated 39 of the 55 survivors (71%). Score evolution (emergency department vs 1y later) is as follows: for the NIHSS, it was 6.2±4.9 versus 3.3±3.9 (z=-3.578; P<.001); and for the mRS score ≤2, it was 54.2% versus 66.7% (χ(2)=14.182; P=.25). The FIM score on discharge from the hospital versus 1 year later was 103.2±28.2 versus 101.7±31.5 (z=-1.008; P=.313). Multivariate analysis showed that aphasia, hemianopia, and incontinence significantly influenced the 1-year FIM score (P<.001). Quality of life, a patient-reported outcome measure of health-related quality of life, was significantly altered concerning vitality, role physical, and role emotional. CONCLUSIONS: One year after a first stroke, despite significant improvement of neurologic impairment, the level of dependency did not change and quality of life was altered. Aphasia, hemianopia, and incontinence significantly influenced functional state.

Seizures in the elderly: development and validation of a diagnostic algorithm.

Seizures are frequent in the elderly, but their diagnosis can be challenging. The objective of this work was to develop and validate an expert-based algorithm for the diagnosis of seizures in elderly people. A multidisciplinary group of neurologists and geriatricians developed a diagnostic algorithm using a combination of selected clinical, electroencephalographical and radiological criteria. The algorithm was validated by multicentre retrospective analysis of data of patients referred for specific symptoms and classified by the experts as epileptic patients or not. The algorithm was applied to all the patients, and the diagnosis provided by the algorithm was compared to the clinical diagnosis of the experts. Twenty-nine clinical, electroencephalographical and radiological criteria were selected for the algorithm. According to criteria combination, seizures were classified in four levels of diagnosis: certain, highly probable, possible or improbable. To validate the algorithm, the medical records of 269 elderly patients were analyzed (138 with epileptic seizures, 131 with non-epileptic manifestations). Patients were mainly referred for a transient focal deficit (40%), confusion (38%), unconsciousness (27%). The algorithm best classified certain and probable seizures versus possible and improbable seizures, with 86.2% sensitivity and 67.2% specificity. Using logistical regression, 2 simplified models were developed, the first with 13 criteria (Se 85.5%, Sp 90.1%), and the second with 7 criteria only (Se 84.8%, Sp 88.6%). In conclusion, the present study validated the use of a revised diagnostic algorithm to help diagnosis epileptic seizures in the elderly. A prospective study is planned to further validate this algorithm.

Reference values of aortic pulse wave velocity in the elderly.

BACKGROUND: Increased aortic pulse wave velocity (AoPWV) is an independent predictor of cardiovascular morbidity and mortality. There are, however, no generally accepted limits for defining the normal or reference values. The aim of the present study was to define reference values for AoPWV. PATIENTS AND METHODS: AoPWV was assessed using applanation tonometry (PulsePen device) in a community living ambulatory population of 455 individuals aged 60-75 years. AoPWV was studied in a group of 206 individuals without hypertension or diabetes, called the 'reference-values group' (RVG), and in a group of 249 individuals with hypertension or diabetes, called the hypertension-diabetes group (HDG). The 95th percentile of the samples was used to determine the upper limit of AoPWV reference values. RESULTS: Mean AoPWV was 8.7+/-2.3 m/s in the RVG and 10.2+/-2.5 m/s in the hypertension-diabetes group (P<0.0001). In the RVG, median AoPWV in the three age subgroups was 8.0 m/s (7.6-8.5) in the 60-64-, 8.0 m/s (7.5-9.0) in the 65-69- and 9.0 m/s (7.9-9.5) in the 70-75-year-old group (NS among groups). In the entire RVG, the upper bounds of the 75th and the 95th percentile of the sample's AoPWV were 10 and 13 m/s, respectively, with no difference between sexes. CONCLUSION: In elderly individuals of 60-75 years, an AoPWV value below 10 m/s, measured with the PulsePen device, can be considered as a normal value. Values of 10-13 m/s can be considered as 'high normal' or 'borderline', whereas an AoPWV above 13 m/s is frankly elevated. This study provides, for the first time in the elderly, reference values of AoPWV.