Modification of the effects of age on clinical outcomes through management of lifestyle-related factors in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: This study examined the association between age and clinical outcomes after ischemic stroke, and whether the effect of age on post-stroke outcomes can be modified by various factors. METHODS: We included 12,171 patients with acute ischemic stroke, who were functionally independent before stroke onset, in a multicenter hospital-based study conducted in Fukuoka, Japan. Patients were categorized into six groups according to age: ≤ 45, 46-55, 56-65, 66-75, 76-85, and > 85 years. Logistic regression analysis was performed to estimate an odds ratio for poor functional outcome (modified Rankin scale score of 3-6 at 3 months) for each age group. Interaction effects of age and various factors were analyzed using a multivariable model. RESULTS: The mean age of the patients was 70.3 ± 12.2 years, and 63.9% were men. Neurological deficits at onset were more severe in the older age groups. The odds ratio of poor functional outcome linearly increased (P for trend <0.001), even after adjusting for potential confounders. Sex, body mass index, hypertension, and diabetes mellitus significantly modified the effect of age on the outcome (P < 0.05). The unfavorable effect of older age was greater in female patients and those with low body weight, whereas the protective effect of younger age was smaller in patients with hypertension or diabetes mellitus. CONCLUSIONS: Functional outcome worsened with age in patients with acute ischemic stroke, especially in females and those with low body weight, hypertension, or hyperglycemia.

Causes of ischemic stroke in young adults versus non-young adults: A multicenter hospital-based observational study.

BACKGROUND: Very few comparative studies have focused on the differences in the causes of ischemic stroke between young adults and non-young adults. This study was performed to determine what causes of ischemic stroke are more important in young adults than in non-young adults using a large-scale multicenter hospital-based stroke registry in Fukuoka, Japan. METHODS AND RESULTS: We investigated data on 15,860 consecutive patients aged ≥18 years with acute ischemic stroke (mean age: 73.5 ± 12.4 years, 58.2% men) who were hospitalized between 2007 and 2019. In total, 779 patients were categorized as young adults (≤50 years of age). Although vascular risk factors, including hypertension, diabetes mellitus, and dyslipidemia, were less frequent in young adults than in non-young adults, the prevalence of diabetes mellitus and dyslipidemia in young adults aged >40 years were comparable to those of non-young adults. Lifestyle-related risk factors such as smoking, drinking, and obesity were more frequent in young adults than in non-young adults. As young adults became older, the proportions of cardioembolism and stroke of other determined etiologies decreased, but those of large-artery atherosclerosis and small-vessel occlusion increased. Some embolic sources (high-risk sources: arterial myxoma, dilated cardiomyopathy, and intracardiac thrombus; medium-risk sources: atrial septal defect, nonbacterial thrombotic endocarditis, patent foramen ovale, and left ventricular hypokinesis) and uncommon causes (vascular diseases: reversible cerebral vasoconstriction syndrome, moyamoya disease, other vascular causes, arterial dissection, and cerebral venous thrombosis; hematologic diseases: antiphospholipid syndrome and protein S deficiency) were more prevalent in young adults than in non-young adults, and these trends decreased with age. CONCLUSIONS: Certain embolic sources and uncommon causes may be etiologically important causes of ischemic stroke in young adults. However, the contribution of conventional vascular risk factors and lifestyle-related risk factors is not negligible with advancing age, even in young adults.

Two Nicotiana occidentalis accessions enable gene identification for Type II hybrid lethality by the cross to N. sylvestris.

Hybrid lethality, meaning the death of F1 hybrid seedlings, has been observed in many plant species, including Nicotiana. Previously, we have revealed that hybrids of the selected Nicotiana occidentalis accession and N. tabacum, an allotetraploid with S and T genomes, exhibited lethality characterized by the fading of shoot color. The lethality was suggested to be controlled by alleles of loci on the S and T genomes derived from N. sylvestris and N. tomentosiformis, respectively. Here, we extended the analysis of hybrid lethality using other two accessions of N. occidentalis identified from the five tested accessions. The two accessions were crossed with N. tabacum and its two progenitors, N. sylvestris and N. tomentosiformis. After crosses with N. tabacum, the two N. occidentalis accessions yielded inviable hybrid seedlings whose lethality was characterized by the fading of shoot color, but only the T genome of N. tabacum was responsible for hybrid lethality. Genetic analysis indicated that first-mentioned N. occidentalis accession carries a single gene causing hybrid lethality by allelic interaction with the S genome.

Epstein-Barr Virus-Associated Encephalopathy Presenting with Nonconvulsive Status Epilepticus in an Immunosuppressive State.

Epstein-Barr virus (EBV) infection is occasionally accompanied by central nervous system (CNS) complications, particularly in immunosuppressed patients. However, the symptoms and clinical features of EBV infection in the CNS are rather heterogeneous and remain unknown. We herein describe the first reported adult case manifesting nonconvulsive status epilepticus (NCSE), possibly associated with reactivation of EBV in an immunosuppressive state. A 63-year-old man with a history of acute myeloid leukemia and taking immunosuppressants was admitted due to progressively impaired consciousness without any focal neurological signs, including paralysis or convulsions. Arterial spin labeling magnetic resonance imaging (ASL-MRI) and brain perfusion single-photon emission computed tomography showed hyperperfusion in the right temporal region, despite no morphological abnormalities in other MRI sequences. White blood cell counts, EBV viral load, and virus-capsid antigen IgG in cerebrospinal fluid were elevated. We diagnosed him with EBV-associated encephalopathy presenting with NCSE. Administration of levetiracetam, an antiepileptic, improved the consciousness and the abnormal hyperperfusion. This case suggests a new concept of EBV-associated encephalopathy leading to epilepsy, particularly in immunosuppressed patients.

Use of Middle Cerebral Artery Visualization with Coronal Computed Tomography to Access Target Artery in Mechanical Thrombectomy.

BACKGROUND: When introducing a microguidewire into an occluded vessel during mechanical thrombectomy (MT), visual information on the vessel course distal to the occluded site could help to avoid perforation. We examined whether visualization of the middle cerebral artery (MCA) by coronal images of nonenhanced computed tomography (coronal CT) provides useful preoperative information on the vessel course in the setting of MT. METHODS AND RESULTS: We retrospectively studied 29 patients with ischemic stroke of the internal carotid artery and MCA occlusion who were admitted to our hospital within 4.5 hours from stroke onset and underwent MT. Coronal CT images were preoperatively created by a dedicated workstation and adjusted to visualize the M1 segment of the MCA (M1) and nearby areas. We referred to these images while performing MT. The shape and course of M1 on preoperative coronal CT images were compared with that in intraoperative angiography after recanalization. The median time from the start of imaging to arterial puncture was 40 minutes (interquartile range: 32.5-55.0 minutes). Successful recanalization of the thrombolysis in cerebral infarction 2b-3 was achieved in 89.7% of patients. The degree of matching was assessed as moderate to excellent, and was useful as preoperative information in 27 (93.1%) patients. CONCLUSIONS: Preoperative information on the vessel course by coronal CT well matched that in the intraoperative angiography. Only a little extra time and a small additional procedure are necessary for this technique. The addition of coronal CT images could contribute to a safe and successful MT.

Usefulness of Transesophageal Echocardiography for Predicting Covert Paroxysmal Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Covert paroxysmal atrial fibrillation (CPAF) is a major cause of embolic stroke of undetermined source (ESUS). However, detecting PAF during hospitalization in these patients is difficult. OBJECTIVES: This study aimed to determine whether findings of transesophageal echocardiography (TEE) during hospitalization are associated with later detection of PAF in patients with ESUS. METHOD: We retrospectively studied 348 patients with ESUS who were admitted to our hospital within 1 week of onset. These patients met the criteria of ESUS, underwent TEE during hospitalization, and were followed up for at least 1 year. RESULTS: We found PAF in 35 (10.0%) patients. In patients with PAF, spontaneous echo contrast (SEC) and low left atrial appendage flow (LAAF) by TEE and enlargement of the left atrial dimension (LAD) by transthoracic echocardiography were identified more frequently compared with those who did not have PAF. In multivariate analysis, SEC and an LAD ≥42 mm were independently associated with later detection of PAF (p < 0.05). An association of LAAF <46.9 cm/s and PAF was marginal (p = 0.09). The specificity of the combined finding of SEC and/or LAAF with that of LAD increased up to 90%, while that of LAD alone was 70%. CONCLUSIONS: The findings of TEE during hospitalization may be useful for identifying patients at increased risk of CPAF in patients with ESUS.

[A case of autoimmune hemolytic anemia diagnosed by occurrence of cardioembolic stroke].

A 79-year-old woman came to us because of sudden onset of dysarthria. She had taken apixaban due to her non-valvular atrial fibrillation. A neurological examination revealed mild facial palsy of her right side, and magnetic resonance imaging showed acute brain infarction at the left frontal lobe. There were no stenotic lesions on intracranial or extracranial magnetic resonance angiography, and she was diagnosed with cardioembolic stroke. Intravenous infusion of heparin and edaravone was initiated, and her neurological symptoms improved. However, she gradually developed jaundice and anemia. Gastro-intestinal bleeding was not observed, and her blood test met the diagnostic criteria for hemolytic anemia. Because both the direct Coombs test and cold agglutinin were positive, she was diagnosed with mixed-type autoimmune hemolytic anemia. Although her serum hemoglobin level decreased to 7.0 g/dl on the 12th hospital day, her anemia gradually improved after steroidal therapy with transfusion. It was revealed that she had shown mild anemia (hemoglobin: 9.2-10.9 g/dl) and hyperbilirubinemia (total bilirubin: 1.8-2.6 mg/dl) for 6 months. Therefore, her latent autoimmune hemolytic anemia became activated with the occurrence of cardioembolic stroke. Autoimmune hemolytic anemia might have promoted cardiac thrombus formation despite the administration of an anticoagulant in this case. It should be noted that autoimmune hemolytic anemia can develop as thrombotic disease. In the present case, autoimmune hemolytic anemia was diagnosed based on the development of cardioembolic stroke.

Association between stroke-like episodes and neuronal hyperexcitability in MELAS with m.3243A>G: A case report.

•The pathophysiology of the stroke-like episodes of MELAS has not completely been elucidated.•Here we report a case of stroke-like episodes, successfully treated with levetiracetam.•Neuronal hyperexcitability can be the underlying mechanism of stroke-like episodes in MELAS.

A case of hyperparathyroidism-associated parkinsonism successfully treated with cinacalcet hydrochloride, a calcimimetic.

BACKGROUND: Some metabolic disorders, including abnormal calcium metabolism, can develop and worsen parkinsonism. However, whether hyperparathyroidism can cause parkinsonism remains controversial. CASE PRESENTATION: An 83-year-old woman with a history of right thalamic hemorrhage and drug-induced parkinsonism, was admitted due to worsening of parkinsonian symptoms including mask-like face, bradykinesia, freezing of gait, and rigidity. She had been diagnosed with autoimmune hepatitis and was being treated with prednisolone. Examinations revealed hypercalcemia (14.3 mg/dL) with an increased level of intact parathyroid hormone (iPTH) (361 pg/mL). Her symptoms were resistant to some additional anti-parkinsonian drugs; however, cinacalcet hydrochloride, a calcimimetic for the treatment of secondary hyperparathyroidism, normalized levels of serum calcium and iPTH, and remarkably improved her symptoms. CONCLUSIONS: In the present case, we speculate that hypercalcemia probably due to secondary hyperparathyroidism that had developed during steroid therapy deteriorated the parkinsonism.

Thrombolytic Therapy in Severe Cardioembolic Stroke After Reversal of Dabigatran with Idarucizumab: Case Report and Literature Review.

Whether idarucizumab, an antidote of dabigatran, can be used effectively and safely before thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in patients with stroke undergoing treatment with dabigatran remains unknown. We herein describe a 57-year-old man who developed severe cardioembolic stroke with a National Institutes of Health Stroke Scale score of 22 in the left middle cerebral artery territory while undergoing treatment with dabigatran for nonvalvular atrial fibrillation and who was treated with rt-PA after the reversal of dabigatran with idarucizumab. The thrombolytic therapy following the use of idarucizumab significantly improved the patient's neurological symptoms without hemorrhagic complications, although acute arterial occlusion of the right lower limb was found during the clinical course.

A Case of Recurrent Ischemic Stroke due to Intravascular Lymphomatosis, Undiagnosed by Random Skin Biopsy and Brain Imaging.

Intravascular lymphoma (IVL) is a rare disease characterized by the proliferation of lymphoma cells in the lumen of the small blood vessels. Although early diagnosis of IVL is important to prolong survival of the patients, its atypical symptoms and clinical course often delay its diagnosis. More than half of the patients are diagnosed at autopsy. We report a 68-year-old man who presented with transient ideomotor apraxia and mildly elevated soluble interleukin-2 receptor levels. He was initially diagnosed with aortogenic embolic stroke. He developed rapidly progressive neurological manifestations with enlargement of brain lesions on brain computed tomography and magnetic resonance imaging and died 3 months after symptom onset. The diagnosis of IVL could not be made by random skin biopsy, but was finally made at autopsy. For the early diagnosis, sufficient random skin biopsy or brain biopsy should be planned when suspected.

A case of cardioembolic stroke due to intracardiac papillary fibroelastoma evaluated by using transesophageal echocardiography.

A 62-year-old woman had a prior ischemic stroke in the right temporal lobe with dysarthria and dysesthesia of the left hand. Embolic stroke of undetermined source (ESUS) was diagnosed and warfarin was administered. However, transient ischemic attack recurred upon admission to our hospital. Paroxysmal atrial fibrillation and cerebral arterial stenotic lesions were absent. Transesophageal echocardiography revealed a mobile hyperechoic structure on the aortic valve indicating papillary fibroelastoma. She was diagnosed with a brain embolism due to the intracardiac tumor which was surgically excised and pathologically confirmed as papillary fibroelastoma. This type of tumor is relatively rare but it is important as an embolic source especially in ESUS. Transesophageal echocardiography was indispensable for detecting the embolic source in this patient with ESUS.