Fernando Díaz-Otero

Familial partial epilepsy with variable foci: clinical features and linkage to chromosome 22q12.

Summary:u2002 Background: Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant syndrome characterized by partial seizures originating from different brain regions in different family members in the absence of detectable structural abnormalities. A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French‐Canadian families.

Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE; MIM 600513) has been associated with mutations in the genes coding for the alfa‐4 (CHRNA4), beta‐2 (CHRNB2), and alpha‐2 (CHRNA2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) and for the corticotropin‐releasing hormone (CRH). A four‐generation ADNFLE family with six affected members was identified. All affected members presented the clinical characteristics of ADNFLE. Interictal awake and sleep EEG recordings showed no epileptiform abnormalities. Ictal video‐EEG recordings showed focal seizures with frontal lobe semiology. Mutation analysis of the CHRNB2 gene revealed a c.859G>A transition (Val287Met) within the second transmembrane domain, identical to that previously described in a Scottish ADNFLE family. To our knowledge, this is the third family reported presenting a mutation in CHRNB2. The clinical phenotype appears similar to that described with mutations in CHRNA4, suggesting that mutations in these two subunits lead to similar functional alterations of the nAChR.

Futile Interhospital Transfer for Endovascular Treatment in Acute Ischemic Stroke The Madrid Stroke Network Experience

Background and Purpose— The complexity of endovascular revascularization treatment (ERT) in acute ischemic stroke and the small number of patients eligible for treatment justify the development of stroke center networks with interhospital patient transfers. However, this approach might result in futile transfers (ie, the transfer of patients who ultimately do not undergo ERT). Our aim was to analyze the frequency of these futile transfers and the reasons for discarding ERT and to identify the possible associated factors. Methods— We analyzed an observational prospective ERT registry from a stroke collaboration ERT network consisting of 3 hospitals. There were interhospital transfers from the first attending hospital to the on-call ERT center for the patients for whom this therapy was indicated, either primarily or after intravenous thrombolysis (drip and shift). Results— The ERT protocol was activated for 199 patients, 129 of whom underwent ERT (64.8%). A total of 120 (60.3%) patients required a hospital transfer, 50 of whom (41%) ultimately did not undergo ERT. There were no differences in their baseline characteristics, the times from stroke onset, or in the delays in interhospital transfers between the transferred patients who were treated and those who were not treated. The main reasons for rejecting ERT after the interhospital transfer were clinical improvement/arterial recanalization (48%) and neuroimaging criteria (32%). Conclusions— Forty-one percent of the ERT transfers were futile, but none of the baseline patient characteristics predicted this result. Futility could be reduced if repetition of unnecessary diagnostic tests was avoided.

Benefits of intravenous thrombolysis in acute ischemic stroke related to extra cranial internal carotid dissection. Dream or reality

Background Small clinical series have reported the safety of intravenous thrombolysis in ischemic stroke related to extracranial internal carotid dissection. However, no studies specifically analyzing the effects on stroke outcome are available. Aims Our goal was to evaluate whether patients with ischemic stroke related to extracranial internal carotid dissection obtain any benefit from intravenous thrombolysis. Methods Multicenter, prospective and observational study conducted in four university hospitals from the Madrid Stroke Network. Consecutive ischemic stroke patients who received intravenous thrombolysis were included, as well as patients with extracranial internal carotid dissection regardless of intravenous thrombolysis treatment. Stroke severity (NIHSS) and three-month outcome (modified Rankin Scale) were compared between the following groups: (1) intravenous thrombolysis-treated patients with ischemic stroke related to extracranial internal carotid dissection vs. other causes of stroke; (2) intravenous thrombolysis-treated extracranial internal carotid dissection patients vs. nonintravenous thrombolysis treated. Outcome was rated at three-months using the modified Rankin Scale. A good outcome was defined as a modified Rankin Scale score ≤2. Results A total of 625 intravenous thrombolysis-treated patients were included; 16 (2·56%) had extracranial internal carotid dissection. Besides, 27 patients with extracranial internal carotid dissection and ischemic stroke who did not receive intravenous thrombolysis were also included. As compared with other etiologies, patients with extracranial internal carotid dissection were younger, had similar stroke severity and showed less improvement in their NIHSS score at Day 7 (1·38; (95% CI −3·77 to 6·54) vs. 6·81; (95% CI −5·99 to 7·63) P=0·004), but without differences in good outcomes at three-months (43·8% vs. 58·2%; NS). Extracranial internal carotid dissection intravenous thrombolysis-treated patients had more severe strokes at admission than those who were nonintravenous thrombolysis treated (median NIHSS: 15 vs. 7; P=0·031). Intravenous thrombolysis was safe in extracranial internal carotid dissection with no symptomatic hemorrhagic events; however, without differences in good outcome compared with the natural course of extracranial internal carotid dissection (nonintravenous thrombolysis treated) after adjustment for stroke severity (46·7% vs. 64·3%; NS). Conclusions As compared with other etiologies, stroke due to extracranial internal carotid dissection seems to obtain similar benefits from intravenous thrombolysis in outcome at three-months. Although intravenous thrombolysis is safe in stroke attributable to extracranial internal carotid dissection, no differences in outcome were found when comparing intravenous thrombolysis treated with nonintravenous thrombolysis-treated patients, even after adjustment for stroke severity.

Familial partial epilepsy with variable foci: a new family with suggestion of linkage to chromosome 22q12.

Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant form of partial epilepsy characterized by the presence of epileptic seizures originating from different cerebral lobes in different members of the same family. Linkage to chromosomes 22q12 and 2q36 has been reported, although only six families have been published. We studied a new FPEVF family including nine affected individuals. The phenotype in this family was similar to that previously described and consisted of nocturnal and daytime seizures with semiology suggesting a frontal lobe origin. A video‐EEG (electroencephalography) recording of the proband’s seizures is presented and revealed hyperkinetic seizures of frontal lobe origin preceded by left frontal spikes. We excluded linkage to chromosome 2q36 and found a suggestion of linkage to chromosome 22q12 with a lod score of 2.64 (θu2003=u20030) for marker D22S689.

Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke

IntroductionReliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization.MethodsData are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, time-lapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24xa0h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90xa0days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability).ResultsIncluded were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45xa0%), primary mechanical thrombectomy (MT; 16xa0%), or combined IVTu2009+u2009MT (39xa0%). Recanalization rate was 71xa0%, median delay of 287xa0min (225; 357). Recanalization was futile in 28xa0% of cases. In an adjusted model, baseline CTA-SI-ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95xa0% CI 0.3–0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95xa0% CI 0.5–1.2). A score ≤5 in CTA-SI-ASPECTS was the best cut-off to predict futile recanalization (sensitivity 35xa0%; specificity 97xa0%; positive predictive value 86xa0%; negative predictive value 77xa0%).ConclusionsCTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapies.

A collaborative system for endovascular treatment of acute ischaemic stroke: the Madrid Stroke Network experience.

The complexity and expense of endovascular treatment (EVT) for acute ischaemic stroke (AIS) can present difficulties in bringing this approach closer to the patients. A collaborative node was implemented involving three stroke centres (SCs) within the Madrid Stroke Network to provide round‐the‐clock access to EVT for AIS.

Intravenous Thrombolytic Treatment in the Oldest Old

Background and Purpose. Intravenous thrombolysis using tissue plasminogen activator is safe and probably effective in patients >80 years old. Nevertheless, its safety has not been specifically addressed for the oldest old patients (≥85 years old, OO). We assessed the safety and effectiveness of thrombolysis in this group of age. Methods. A prospective registry of patients treated with intravenous thrombolysis. Patients were divided in two groups (<85 years and the OO). Demographic data, stroke aetiology and baseline National Institute Health Stroke Scale (NIHSS) score were recorded. The primary outcome measures were the percentage of symptomatic intracranial haemorrhage (SICH) and functional outcome at 3 months (modified Rankin Scale, mRS). Results. A total of 1,505 patients were registered. 106 patients were OO [median 88, range 85–101]. Female sex, hypertension, elevated blood pressure at admission, cardioembolic strokes and higher basal NIHSS score were more frequent in the OO. SICH transformation rates were similar (3.1% versus 3.7%, P = 1.00). The probability of independence at 3 months (mRS 0–2) was lower in the OO (40.2% versus 58.7%, P = 0.001) but not after adjustment for confounding factors (adjusted OR, 0.82; 95% CI, 0.50 to 1.37; P = 0.455). Three-month mortality was higher in the OO (28.0% versus 11.5%, P < 0.001). Conclusion. Intravenous thrombolysis for stroke in OO patients did not increase the risk of SICH although mortality was higher in this group.

Tissue plasminogen activator for acute ischemic stroke: calculation of dose based on estimated patient weight can increase the risk of cerebral bleeding.

A dose of 0.9xa0mg/kg of intravenous tissue plasminogen activator (t-PA) has proven to be beneficial in the treatment of acute ischemic stroke (AIS). Dosing of t-PA based on estimated patient weight (PW) increases the likelihood of errors. Our objectives were to evaluate the accuracy of estimated PW and assess the effectiveness and safety of the actual applied dose (AAD) of t-PA. We performed a prospective single-center study of AIS patients treated with t-PA from May 2010 to December 2011. Dose was calculated according to estimated PW. Patients were weighed during the 24xa0h following treatment with t-PA. Estimation errors and AAD were calculated. Actual PW was measured in 97 of the 108 included patients. PW estimation errors were recorded in 22.7xa0% and were more frequent when weight was estimated by stroke unit staff (44xa0%). Only 11xa0% of patients misreported their own weight. Mean AAD was significantly higher in patients who had intracerebral hemorrhage (ICH) after t-PA than in patients who did not (0.96 vs. 0.92xa0mg/kg; pxa0=xa00.02). Multivariate analysis showed an increased risk of ICH for each 10xa0% increase in t-PA dose above the optimal dose of 0.90xa0mg/kg (OR 3.10; 95xa0% CI 1.14–8.39; pxa0=xa00.026). No effects of t-PA misdosing were observed on symptomatic ICH, functional outcome or mortality. Estimated PW is frequently inaccurate and leads to t-PA dosing errors. Increasing doses of t-PA above 0.90xa0mg/kg may increase the risk of ICH. Standardized weighing methods before t-PA is administered should be considered.

Mechanical thrombectomy in patients with medical contraindications for intravenous thrombolysis: a prospective observational study

Background and purpose The present study was conducted with the objective of evaluating the safety of primary mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke and comorbidities that preclude treatment with IV thrombolysis (IVT), compared with patients who received standard IVT treatment followed by MT. Secondary objectives were to analyse the recanalization rate and outcomes. Methods A prospective observational multicenter study (FUN-TPA) that recruited patients treated within 4.5u2005hours of symptom onset was performed. Treatments were IVT followed by MT if occlusion persisted, or primary MT when IVT was contraindicated. Outcome measures were procedural complications, symptomatic intracranial hemorrhage (SICH), recanalization rate, National Institutes of Health Stroke Scale (NIHSS) score at 7u2005days, modified Rankin Scale (mRS) score and mortality at 90u2005days. Results Of 131 patients, 21 (16%) had medical contraindications for IVT and were treated primarily with MT whereas 110 (84%) underwent IVT, followed by MT in 53 cases (40%). The recanalization rate and procedural complications were similar in the two groups. There were no SICHs after primary MT vs 3 (6%) after IVT+MT. Nine patients (43%) in the primary MT group achieved independence (mRS 0–2) compared with 36 (68%) in the IVT+MT group (p=0.046). Mortality rates in the two groups were 14% (n=3) vs 4% (n=2) (p=0.13). Adjusted ORs for independence in patients receiving standard IVT+MT vs MT in patients with medical contraindications for IVT were 2.8 (95% CI 0.99 to 7.98) and 0.24 (95% CI 0.04 to 1.52) for mortality. Conclusions MT is safe in patients with potential comorbidity-derived risks that preclude IVT. MT should be offered, aiming for prompt recanalization, to patients with LVO stroke unsuitable for IVT. Trial registration number NCT02164357; Results.