Use of Tenecteplase in Acute Ischemic Stroke in the Time of SARS-CoV-2.

Tenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.25 mg/kg) between March 2020 and February 2021. A comparative analysis was made to compare patient treatment times and prognosis. A total of 117 patients treated with alteplase and 92 with TNK were included. No significant differences were observed in age, main vascular risk factors or previous treatments. The median National Institutes of Health Stroke Scale was 8 in the alteplase group and 10 in those treated with TNK (P = .13). Combined treatment with mechanical thrombectomy was performed in 47% in the alteplase group and 46.7% in the TNK group; Thrombolysis In Cerebral Infarction scale 2b-3 recanalization was achieved in 83% and 90.7%, respectively (P = .30). There was a decrease in onset-to-needle median time (165 min vs 140 min, P < .01) and no significant variations in door-needle median time. There was no significant difference in the incidence of symptomatic hemorrhagic transformation in mortality or functional independence at 3 months. The easier administration of TNK has improved the accessibility of fibrinolytic therapy, even in adverse circumstances, such as the COVID-19 pandemic. Its use appears to be safe and effective, even in patients who are not candidates for mechanical thrombectomy.

Hereditary cerebral small vessel disease: Assessment of a HTRA1 variant using protein stability predictors and 3D modelling.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive vascular disorder caused by biallellic variants in HTRA1. Recently, it has been reported that several heterozygous mutations in HTRA1 are responsible for a milder late-onset cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. The majority of them are missense that affects the Htr1A protease activity due to a dominant-negative effect caused by defective trimerization or monomer activation. The molecular mechanism related to the structural destabilization of the protein supports the practical utility of integrating computational stability predictors to prioritize candidate variants in this gene. In this work, we report a family with several members diagnosed with subcortical ischemic events and progressive cognitive impairment caused by the novel c.820C > G, p.(Arg274Gly) heterozygous variant in HTRA1 segregating in an autosomal dominant manner and propose its molecular mechanism by a three-dimensional model of the protein's structure.

Presence of Extra-Criteria Antiphospholipid Antibodies Is an Independent Risk Factor for Ischemic Stroke.

Background: Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-ß2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors. Materials and Methods: A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182). Results: The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03-5.53), dyslipidemia (OR 1.70, 95% CI: 1.01-2.84), arterial hypertension (OR 1.82, 95% CI: 1.03-3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90-9.78), and active smoking (OR 3.47, 95% CI: 1.72-6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75). Conclusions: IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.

Pure alexia: two cases and a new neuroanatomical classification.

Pure alexia without visual or language accompanying deficits (isolated pure alexia), represents an infrequent finding in clinical practice. It has been linked to lesions involving the splenium of the callosal corpus in classical descriptions; however, it has also been reported after occipito-temporal cortex damage in the absence of white matter implication. In this regard, a functional region called the visual word form area has been recently related to the posterior aspect of the occipitotemporal gyrus. We report two new cases of cortical hematomas leading to this rare condition and we discuss the neuroanatomical evolution of this syndrome. Finally, we propose a new classification of pure alexia based on the neuroanatomical location of the lesion, namely: (1) disconnection alexia, after posterior and dorsal lesions involving the splenium of the callosal corpus or the paraventricular white matter, often associated with visual deficits, and (2) cortical alexia, after more anterior and ventral lesions in the occipito-temporal cortex with damage of the visual word form area, that usually manifests as isolated pure alexia.

Síndrome de oreja roja: a propósito de un caso con buena respuesta terapéutica / Red ear syndrome: a case report with good therapeutic response

No disponible

Symptomatic Atherosclerotic Disease and Decreased Risk of Cancer-Specific Mortality: A Prospective, Population-Based Study (NEDICES).

The few studies that have assessed the association between symptomatic atherosclerotic disease and risk of cancer have had conflicting results. In addition, these studies ascertained participants either from treatment settings (ie, service-based studies) or by using a records linkage system (ie, medical records of patients evaluated at clinics or hospitals) and, therefore, were prone to selection bias. Our purpose was to estimate the risk of cancer mortality in a large population-based sample of elderly people, comparing participants with symptomatic atherosclerotic disease (atherosclerotic stroke and coronary disease) to their counterparts without symptomatic atherosclerotic disease (ie, controls) in the same population.In this population-based, prospective study (Neurological Disorders of Central Spain, NEDICES), 5262 elderly community-dwelling participants with and without symptomatic atherosclerotic disease were identified and followed for a median of 12.1 years, after which the death certificates of those who died were reviewed.A total of 2701 (53.3%) of 5262 participants died, including 314 (68.6%) of 458 participants with symptomatic atherosclerotic disease and 2387 (49.7%) of 4804 controls. Cancer mortality was reported significantly less often in those with symptomatic atherosclerotic disease (15.6%) than in controls (25.6%) (P < 0.001). In an unadjusted Cox model, risk of cancer-specific mortality was decreased in participants with symptomatic atherosclerotic disease (HR = 0.74, 95% confidence interval [CI], 0.55-0.98, P = 0.04) vs. those without symptomatic atherosclerotic disease (reference group). In an adjusted Cox model, HR = 0.58; 95% CI, 0.38-0.89; P = 0.01.This population-based, prospective study suggests that there is an inverse association between symptomatic atherosclerotic disease and risk of cancer mortality.

Higher glutamate to glutamine ratios in occipital regions in women with migraine during the interictal state.

BACKGROUND: Glutamate (Glu) and glutamine (Gln) are strongly compartmentalized (in neurons for Glu and in astrocytes for Gln). The visual cortex is the brain region with a higher neuron/astrocyte ratio (the highest neuronal density and the relatively lowest density of astrocytes). Elevations in extracellular Glu or potassium above certain thresholds are likely candidates to be the final common steps in the multiple distinct processes that can lead to cortical spreading depression. Astrocytes play a key role in this phenomenon, by acting as a sink for extracellular Glu and potassium, as well as generally acting as a buffer for the ionic and neurochemical changes that initiate and propagate cortical spreading depression. OBJECTIVE: The purpose of this study was to quantify Glu and Gln to generate Glu/Gln ratios in women with migraine during the interictal state compared with healthy control women. METHODS: Twenty-seven patients with migraine (8 with aura and 19 without aura) and 19 matched healthy controls were included in the study. We performed proton magnetic resonance spectroscopy in the anterior paracingulate cortex and occipital cortex (OC). Spectral analysis was performed by LCModel, allowing a separation of Glu and Gln using a 3T machine. RESULTS: The main result was a significantly higher Glu/Gln ratio in the OC of migraine patients compared with healthy control subjects (4.87 for migraineurs [standard deviation (SD) = 2.74] and 3.42 for controls [SD = 1.52], P = .042). We also observed higher Glu levels (6.98 for migraineurs [SD = 0.85] and 6.22 for controls [SD = 0.97], P = .007) and Glu/creatine + phosphocreatine ratio (1.18 for migraineurs [SD = 0.18] and 1.00 for controls [SD = 0.16], P = .001) in anterior paracingulate cortex in migraine patients but saw no differences in Glu/Gln ratio (2.79 for migraineurs [SD = 1.11] and 2.63 for controls [SD = 1.61], P = .68). CONCLUSION: These findings are consistent with glutamatergic differences in migraine patients during the interictal period compared with healthy controls. We hypothesize that an increased Glu/Gln ratio could arise from neuronal-glial coupling of glutamatergic metabolism differences or an increased neuron/astrocyte ratio in the OC.

Cognitive and behavioral profile in females with epilepsy with PDCH19 mutation: two novel mutations and review of the literature.

Mutation in the protocadherin 19 (PCDH19) gene is an increasingly recognized cause of epilepsy in females. This disorder is frequently associated with mental retardation and psychiatric features. We describe two unrelated females with novel PCDH19 missense mutations. One was de novo, and the other was inherited from her unaffected father. Both had mild mental impairment but had remarkable behavioral problems. We reviewed the cognitive and behavioral profiles of previously reported PCDH19-positive cases. Intellectual disability appeared in 75% of patients, ranging from borderline to severe. More than half of the individuals presented behavioral disturbances, which could be divided into two different groups: autistic and non-autistic. The majority of patients with autism already had some degree of cognitive impairment. It appears that seizures tend to diminish or even stop in adolescence, so non-epileptic problems can become the most important and disabling issue in adult patients with PCDH19 mutation.

Cerebrovascular disease incidence in central Spain (NEDICES): a population-based prospective study.

BACKGROUND: Stroke is one of the most disabling and burdensome health conditions worldwide, but no prospective population-based study has been conducted in Spain. Our aim was to assess age- and gender incidence rates of cerebrovascular disease, including stroke and transient ischemic attack, in three populations in central Spain using data from the NEDICES (Neurological Diseases in Central Spain), a population-based survey of elderly participants. METHODS: Individuals were evaluated at baseline (1994-1995) and at follow-up (a median of 3.2 years later in 1997-1998). The evaluation included a screening questionnaire for stroke and a neurological assessment (when possible). RESULTS: Of 5278 participants evaluated at baseline, there were 257 prevalent stroke cases. Seventy-five incident patients with cerebrovascular disease (57 stroke cases and 18 transient ischemic attacks cases) were identified among 3914 individuals assessed at follow-up. Average annual incidence rate (per 1000 person-years) in the population aged 65 to 85 and over years, adjusted to the standard European population, was 5.1 (95% CI, 3.7 to 6.6) for all types of cerebrovascular disease. Age-specific incidence rates of cerebrovascular disease increased with advancing age. Age and diabetes mellitus were independent risk factors for cerebrovascular disease. Number of vascular risk factors present at baseline showed an independent positive and graded association with incident cerebrovascular disease. CONCLUSIONS: In the NEDICES study, incidence of cerebrovascular disease increased with age beyond age 85. Our incidence rates provide new estimates for projection of future burden of disease in Spain.

Información sobre enfermedades del sistema circulatorio en España / Information about vascular diseases (cardiac and cerebral) in Spain

No disponible

No disponible

Akinetic mutism induced by tacrolimus.

Akinetic mutism is an uncommon clinical syndrome characterized by the inability to produce voluntary movements or speech without loss of awareness. Cerebrovascular diseases are the most frequent etiology. It has been reported in cyclosporine-related neurotoxicity, but it is exceptional as the presenting form of tacrolimus intoxication. We report the case of a 66-year-old man who underwent an orthotopic liver transplantation and was treated with intravenous methylprednisolone and tacrolimus. He had an uneventful postoperative course until the third day after surgery, when he developed acute onset mutism, akinesia, and waxy rigidity of passive limb movements. His arterial blood pressure and temperature were normal. Blood analysis and a magnetic resonance image of the brain showed no acute abnormalities. Serum levels of tacrolimus were 20.8 ng/mL, so it was substituted by cyclosporine and mycophenolate mofetil with progressive and complete recovery of akinetic mutism during the following days. Akinetic mutism is an exceptional manifestation of tacrolimus neurotoxicity, but early recognition of the syndrome and withdrawal of the drug are important to avoid persistent cerebral lesions.

Diagnóstico y tratamiento del dolor neuropático / Diagnosis and treatment of the neuropathic pain

No disponible

No disponible

Venous angioma associated with atypical ophthalmoplegic migraine.

BACKGROUND: Ophthalmoplegic migraine is a rare syndrome in which episodic headaches are associated with ophthalmoplegia. Several recent reports emphasize the possibility, especially in atypical cases, of a heterogeneous type of ophthalmoplegic migraine. METHODS: We describe the case of an 18-year-old woman with recurrent episodic headache accompanied by binocular diplopia due to left third cranial nerve palsy. The symptoms resolve in hours. A diagnosis of atypical ophthalmoplegic migraine was established. RESULTS: Digital angiography revealed a venous angioma draining into the left cavernous sinus. CONCLUSIONS: This case reveals the importance of differential diagnosis in atypical migraine in which the symptomatology could be secondary to intracranial lesions. We propose venous stasis as a cause of symptoms.