Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Unwanted detachment of the Solitaire device during mechanical thrombectomy in acute ischemic stroke.

BACKGROUND: The use of retrievable stents for endovascular clot retrieval has dramatically improved successful revascularization and clinical outcome in selected patients with acute stroke. OBJECTIVE: To describe the rate and clinical consequences of unwanted spontaneous detachment of these devices during mechanical thrombectomy. METHODS: We studied 262 consecutive patients treated with the retrievable stent, Solitaire, for acute ischemic stroke between November 2008 and April 2015. Clinical, procedural, and outcome variables were compared between patients with and without unexpected detachment of this device. Detachment was classified as proximal to the stent proximal marker (type A) or distal to the marker (type B). Poor functional outcome was defined as modified Rankin scale score >2 at 90 days. RESULTS: Unwanted detachment occurred in 6/262 (2.3%) cases, four of type A and two of type B. Stent recovery was possible in three patients, all of 'type A', but in none of 'type B'. The number of prior passes was higher in patients with undesired detachment (3 (2-5) vs 2 (1-3), p=0.007). Detachment was associated with higher rate of symptomatic intracranial hemorrhage (SICH) (33.3% vs 4.3%, p=0.001), poorer outcome (100% vs 54.8%, p=0.028), and higher mortality rate at 90 days (50% vs 17%, p=0.038). CONCLUSIONS: Unwanted detachment of a Solitaire is an uncommon complication during mechanical thrombectomy in patients with acute ischemic stroke and is associated with the clot retrieval attempts, SICH, poor outcome, and higher mortality.

Preliminary experience with the Pipeline Flex Embolization Device: technical note.

BACKGROUND: Clinical experience with the Pipeline Embolization Device (PED) has been widely described in the literature since it obtained its European CE and FDA approvals in 2008 and 2011, respectively. The new generation of PED, the Pipeline Flex Embolization Device, received the CE mark of approval in March 2014. While the implant composition has not changed, its new delivery system has some differences. One of the main changes from the previous generation is a new delivery system that makes the device resheathable until deployed over 90% of its length. We present our preliminary experience using this device. METHODS: Between May and June 2014, six patients with six aneurysms were treated with the Pipeline Flex device. RESULTS: All devices were placed properly, without technical difficulties. We successfully resheathed and repositioned the device in two cases. Minor and major intraprocedural or periprocedural events were noted. CONCLUSIONS: The Pipeline Flex device allows more precise and controlled deployment than the current PED device. Although this preliminary experience seems positive, multicenter larger series will be needed to confirm the safety and durability of this new device.

Impact of a comprehensive stroke centre on the care of patients with acute ischaemic stroke due to cervical artery dissection.

INTRODUCTION: Cervical artery dissection (CAD) is the cause of 2% to 3% of ischaemic strokes and 10% to 25% of the ischaemic strokes in young people. Our objective is to evaluate whether implementation of a comprehensive stroke centre (CSC) improves the diagnosis and modifies the prognosis of patients with acute stroke due to CAD. PATIENTS AND METHODS: Retrospective study of a registry of consecutive patients with acute stroke due to CAD. They were classified according to the period of care at our centre: pre-CSC (October 2004-March 2008, 42 months) or post-CSC (April 2008-June 2012, 51 months). We compared baseline characteristics, methods of diagnosis, treatment and outcome of these patients in both periods. RESULTS: Nine patients were diagnosed with CAD in pre-CSC and 26 in post-CSC, representing 0.8% and 2.1% of all ischaemic strokes treated in each period, respectively. The diagnosis of CAD was made within the first 24 hours in 42.3% of the patients in post-CSC versus 0% in pre-CSC, by using urgent cerebral angiography as a diagnostic test in 46.2% of cases in the second period compared to 0% in the first. Both severity of stroke (median NIHSS score 11 vs. 3, P=.014) and time to neurological care (265 min vs 148, P=.056) were higher in the post-CSC period. Endovascular treatment was performed in 34.3%, and all treatments were post-CSC. The functional outcome was comparable for both periods. CONCLUSIONS: Implementation of a CSC increases the frequency of the diagnosis of CAD, as well as the treatment options for these patients in the acute phase of stroke.

Safety and effectiveness of endovascular treatment of stroke with unknown time of onset.

BACKGROUND: Currently, treatment options for patients with strokes with unknown time of onset (UKO) remain limited. With the advance of neuroimaging and endovascular treatment (EVT), selected patients might have a chance of a therapeutic option. We sought to compare clinical outcome after EVT in patients with known time of stroke onset (KO) and in those with UKO. METHODS: We prospectively registered consecutive patients with acute large artery occlusion of the anterior territory who underwent EVT. Multimodal MR or Alberta Stroke Program early CT score (ASPECTS) and transcranial color-coded Duplex sonography were used to select patients for EVT. Recanalization, periprocedural complications, intracranial hemorrhage (ICH) and outcome were recorded. Symptomatic ICH (sICH) was defined as a worsening of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 h in any bleeding. Favorable outcome was defined as a modified Rankin score ≤2 at 3 months. RESULTS: A total of 141 patients were studied, 109 with KO and 32 with UKO. Mean age was 66.5 versus 64.7 years (p = 0.005) and median baseline NIHSS was 18 versus 17 (p = 0.095), respectively. Prior IV tPA was more frequently administered to KO patients (62.4 vs. 9.4%, p < 0.001), whereas patient selection using multimodal MR was more frequent in patients with UKO (78.1 vs. 45.4%, p < 0.001). Median time from stroke onset or from the last time the patient was seen well to groin puncture and to recanalization was significantly longer in patients with UKO, but no differences were found in the duration of the procedure. For KO/UKO patients recanalization was seen in 77.1 vs. 65.7% (p = 0.084), sICH occurred in 10 versus 0% (p = 0.061) and favorable outcome at 3 months was achieved in 41.3 versus 50% (p = 0.382), respectively. CONCLUSIONS: Clinical outcomes in this series of EVT in ischemic stroke patients due to large anterior arterial occlusion with salvageable brain are similar for patients treated with KO and UKO. These data support a randomized study of EVT in extended or uncertain time windows..

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

BACKGROUND: Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. METHODS: We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. RESULTS: Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. CONCLUSION: Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis.

Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis.

BACKGROUND AND PURPOSE: Perfusion-computed tomography-source images (PCT-SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT-SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis. METHODS: We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color-coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT-SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2-3) vs. poor (scores 0-1) collaterals. The predetermined primary end-point was a good 3-month functional outcome, while early neurological recovery, transcranial duplex-assessed 24-h MCA recanalization, 24-h hypodensity volume and hemorrhagic transformation were considered secondary end-points. RESULTS: Fifty-four patients were included (55.5% women, median NIHSS 10), and 4-13-23-14 patients had LMC score (LMCs) of 0-1-2-3, respectively. The probability of a good long-term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good-LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23-197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate. CONCLUSIONS: A higher degree of LMC assessed by PCT-SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.

[Perfusion computed tomography makes it possible to overcome important SITS-MOST exclusion criteria for the endovenous thrombolysis of cerebral infarction]. / La tomografia computarizada de perfusion permite superar importantes criterios de exclusion SITS-MOST para la trombolisis endovenosa del infarto cerebral.

AIM. To study the frequency, safety and efficacy of perfusion computed tomography (PCT), through identification of brain tissue-at-risk, to guide intravenous thrombolysis in stroke patients with regulatory exclusion criteria (SITS-MOST and ECASS-3). PATIENTS AND METHODS. We studied consecutive acute non-lacunar ischemic stroke patients. After conventional CT was considered eligible, PCT was performed in the following circumstances: 4.5 to 6 h window, wake-up stroke or unknown time of onset; extent early infarct signs on CT; minor or severe stroke; seizures or loss of consciousness. Intravenous 0.9 mg/kg alteplase was indicated if: cerebral blood volume lesion covered < 1/3 of middle cerebral artery territory; mismatch > 20% between mean transit time and cerebral blood volume maps existed; and informed consent. SITS-MOST safety-efficacy parameters were used as endpoint variables. RESULTS. Between May 2009-April 2010, 66 hyperacute ischemic stroke patients a priori not eligible for intravenous thrombolysis underwent PCT. Indications were: > 4.5 h in 18 patients, wake up stroke or unknown onset in 25, extent infarct signs in 6, seizures at onset in 11, and minor stroke (NIHSS < 4) in 6. Twenty-nine (44%) of them finally received intravenous thrombolysis. Symptomatic hemorrhagic transformation occurred in 2 (6.9%) patient and 18 (62.1%) achieved a modified Rankin scale score equal or less than 2 on day 90. CONCLUSION. A high proportion of acute stroke patients with SITS-MOST and ECASS-3 exclusion criteria can be safely and efficaciously treated with intravenous thrombolysis using a PCT selection protocol. However randomized control trials will be needed to confirm our results.

A single center experience of stenting in symptomatic intracranial atherosclerosis.

Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has been compared with medical management in a randomized trial (SAMMPRIS), where aggressive medical management was superior to PTAS with the use of the Wingspan stent system, however in our experience we have had good results and have experienced no complications with this therapy. In a retrospective, single-center study we enrolled seven consecutive patients with a symptomatic angiographically proven atherosclerotic intracranial arterial stenosis of the anterior and posterior circulation. All cases received adjuvant therapy (aspirin and clopidogrel or ticlopidine) before and after deployment of the device. The procedures were performed with the patient under general anesthesia. We use the Wingspan stent system. The occlusion site was middle cerebral artery (MCA) in three patients, proximal internal carotid artery (ICA) in one patient and vertebrobasilar artery in three patients. Primary interventional successful revascularization was achieved in all cases. Four patients had no residual stenosis, and the other three had 20%, 30% and 40% residual stenosis (Table 1). All patients showed a clinical improvement after stent deployment. No peri-interventional events or neurologic complications occurred directly related to the technique. Patency rate was 100% at the last examination in six cases, one case had a pre-occlusive stenosis, requiring angioplasty. No patients died during the follow-up period, and 100% of patients showed good functional outcome at three months (modified Rankin Scale score ≤ 2). Although the SAMMPRIS study showed that aggressive medical management was superior to PTAS, our results suggest that intracranial stenting is safe and effective, probably due to an extraordinary selection of candidates and to an exquisite technique.

[Stiff-person syndrome: a case report]. / Síndrome de la persona rígida: a propósito de un caso.

INTRODUCTION: Stiff-person (stiff-man) syndrome is characterised by symptoms of muscular rigidity and spasms, which are generally of an axial nature. Involuntary contractions of the agonist and antagonist muscles caused by activity of the motor units during rest are the main clinical and electrophysiological marker of the disease. The nature of the syndrome is considered to be autoimmune, with positive glutamic acid decarboxylase (anti-GAD) antibodies in most patients. These antibodies exert an influence over GABAergic transmission. CASE REPORT: A 29-year-old female who was admitted to hospital with a diagnosis of psychogenic mutism. While in hospital the patient developed a clinical picture consisting in generalised stiffness that was predominantly axial and proximal with hyperreflexia in the four limbs and strong contraction of the muscles of the abdomen. The most striking lab finding was the presence of anti-GAD, anti-parietal cells, anti-microsomal/TPO and antithyroglobulin antibodies, together with oligoclonal immunoglobulin G bands in the cerebrospinal fluid. Treatment was established with benzodiazepines, antispastic agents and corticosteroids, and the clinical symptoms progressively improved until they had partially remitted at two months. The lab findings and clinical features are compatible with stiff-person syndrome in a patient with associated psychiatric comorbidity. CONCLUSIONS: Anti-GAD antibodies are not exclusive to stiff-person syndrome and can also be found in a number of other autoimmune disorders. Other mechanisms which can also produce a dysfunction of the GABAergic system have also been suggested. The syndrome can be difficult to diagnose from the clinical point of view and it must therefore be borne in mind in patients who begin with unexplainable stiffness and spasms because it is a potentially treatable pathology.

[Some reflections on the pathophysiology of abnormal movements]. / Algunas reflexiones sobre la patofisiología de los movimientos anormales.

INTRODUCTION: The field of abnormal movements is an area that is in continual expansion within Neurology and treatment is currently available for many of them, at least as far as the symptoms are concerned. Yet, the exact mechanisms of operation of the neurological structures involved in movement are not fully understood. DEVELOPMENT: It seems clear that the basal ganglia play an important role, fundamentally in pseudo-automatic movements, but because they are interconnected with many other structures it is difficult to gain a precise understanding of their individual functions. There are theories based solely on anatomical data, which are not enough to account for everything. The theory of the existence of neuronal circuits seems to explain a wider part of movement, although it still has a number of shortcomings. Another theory of movement disorders is that based on neurochemistry, according to which the imbalance of certain neurotransmitters would be the causation of the disease, but this theory does not enable us to explain all the pathologies related to movement either. A number of clinical observations and the use of animal models, however, have made it possible to draw up pathophysiological hypotheses about the generation of some abnormal movements. CONCLUSIONS: All these approaches have enabled researchers to find symptomatic treatments for certain diseases, but our knowledge of the pathophysiology involved is still far from complete and the chances of enhancing the therapeutic capacity available in such cases in the future are therefore immense.