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1.
J Stroke Cerebrovasc Dis ; 30(6): 105761, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33813084

RESUMO

OBJECTIVES: Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke in several animal models. After a phase I study in healthy volunteers, two phase II trials of AM for inflammatory bowel diseases have been recently completed. The current AdrenoMedullin For Ischemic Stroke (AMFIS) study aims to assess the safety and efficacy of AM in patients with acute ischemic stroke. MATERIALS AND METHODS: The AMFIS study is an investigator-initiated, randomized, double-blind, phase-II trial. AM or placebo will be administered to patients with non-cardioembolic ischemic stroke within 24 h after stroke onset. In the first cohort of the AMFIS study, patients will be randomly allocated to the investigation treatment A (30 µg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10). In the second cohort, patients will be assigned to the investigation treatment B (56 µg/kg of AM in total for 7 days, n = 20) or placebo group (n = 10). RESULTS: Serious adverse events related to the protocol treatment will be evaluated as the primary outcome. All adverse events will be analyzed as the secondary outcome. Regarding efficacy endpoints, the change in National Institutes of Health Stroke Scale and modified Rankin Scale scores will be compared between investigation treatment and placebo groups. CONCLUSIONS: AM is expected to be a safe and effective treatment for ischemic stroke.

2.
Int J Med Sci ; 18(10): 2162-2165, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859523

RESUMO

Bow hunter's syndrome (BHS) should not be overlooked as a cause of cerebral infarction in the posterior circulation. However, covert BHS, which does not impair blood flow with simple rotation but only at certain angles, may make the diagnosis of BHS difficult. We propose a new algorithm to detect BHS or covert BHS. We recommend that BHS and covert BHS be detected by noninvasive duplex ultrasonography, which will allow for appropriate treatment.

3.
Neurochem Int ; 146: 105015, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33781849

RESUMO

Reliable quantitative blood biomarkers are important in vascular dementia (VaD) because early diagnosis and therapeutic intervention are effective in preventing progression of dementia. Although many blood biomarkers for acute ischemic stroke (AIS) or VaD have been reported, there are few reliable blood biomarkers. VaD and AIS have similar pathological conditions that are associated with small vessel disease (SVD) such as oxidative stress, inflammation, endothelial dysfunction, and neuronal injury. Therefore, it may be possible to find superior blood biomarkers of VaD among AIS blood biomarkers. Owing to recent developments, noncoding RNAs such as microRNA and long noncoding RNA, which can be analyzed using a single drop of blood, are also particularly reliable VaD markers because they stably reflect brain tissue damage. A multimarker combining several blood biomarkers or artificial intelligence technology may also be beneficial to compensate for insufficiencies of a single blood biomarker. This review describes the blood biomarkers of VaD and how they are related to blood biomarkers of AIS.

4.
Intern Med ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33642490

RESUMO

A 54-year-old man suddenly developed impaired consciousness and left hemiplegia due to a right thalamic hematoma. Emergent ventricular drainage for acute hydrocephalus improved the level of consciousness, but macrosquare-wave jerks (MSWJ) consisting of a right-ward intrusive saccade and corrective saccade appeared. The MSWJ disappeared on day 2 when follow-up CT revealed improvement of hydrocephalus. However, on day 36, after ventricular drainage was clamped, the MSWJ reappeared. After ventriculoperitoneal shunt, MSWJ again subsided. In this patient, hydrocephalus may have stretched the superior colliculus, thereby decreasing activity of the fixation neurons and then omnipause neurons, and eventually resulting in the reversible MSWJ.

5.
Sci Rep ; 11(1): 7127, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782508

RESUMO

The detection of underlying atrial fibrillation (AF) has become increasingly possible by insertable cardiac monitoring (ICM). During hospitalization for cryptogenic stroke, factors related to the early and late development of AF have not been studied. CHALLENGE ESUS/CS is a multicenter registry of cryptogenic stroke patients undergoing transesophageal echocardiography. Twelve-lead electrocardiogram, continuous cardiac monitoring, and 24-h Holter electrocardiogram were all used for the detection of AF. Early and late detection of AF was determined with an allocation ratio of 1:1 among patients with AF. A total of 677 patients (68.7 ± 12.8 years; 455 men) were enrolled, and 64 patients developed AF during hospitalization. Four days after admission was identified as the approximate median day to classify early and late phases to detect AF: ≤ 4 days, 37 patients; > 4 days, 27 patients. Multiple logistic regression analysis showed that spontaneous echo contrast (SEC) (OR 5.91; 95% CI 2.19-15.97; p < 0.001) was associated with AF ≤ 4 days, whereas a large infarction > 3 cm in diameter (OR 3.28; 95% CI 1.35-7.97; p = 0.009) was associated with AF > 4 days. SEC and large infarctions were important predictors of in-hospital AF detection, particularly in the early and late stages, respectively; thus, they could serve as indications for recommending ICM.

6.
J Stroke Cerebrovasc Dis ; 30(4): 105656, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33571877

RESUMO

OBJECTIVES: Post-stroke complications affect stroke survivors across the world, although data on them are limited. We conducted a questionnaire survey to examine the real-world state and issues regarding post-stroke complications in Japan, which represents a super-aged society. MATERIALS AND METHODS: In 2018, a nationwide multi-center questionnaire survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated. Three questionnaires regarding post-stroke complications were mailed to the doctors responsible for stroke management. RESULTS: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The number of stroke patients in the departments of neurology and neurosurgery was 338.3 ± 195.3 and 295.8 ± 121.8. Hospitals were classified using the categories secondary (n =142) and tertiary hospitals (n = 106); most hospitals were acute hospitals. Dementia was the most common complication (30.9%), followed by dysphagia (29.3%), and apathy (16.3%). Dementia was thought to be more common by neurologists than neurosurgeons, while apathy and bladder-rectal disorder were thought to be more common by neurosurgeons than neurologists (p = 0.001). The most difficult complication to treat was dysphagia (40.4%), followed by dementia (33.9%), epilepsy (4.1%), and fall (4.1%). Dementia was considered to lack clinical evidence regarding treatment (32.8%), followed by dysphagia (25.3%), and epilepsy (14.1%). Epilepsy was considered to lack clinical evidence among hospitals with a larger number of stroke cases (p = 0.044). CONCLUSION: This study revealed the current state and issues regarding post-stroke complications in Japan. Clinicians should be aware of the importance of post-stroke complications, although data on them remain unsatisfactory.


Assuntos
Afasia/epidemiologia , Demência/epidemiologia , Epilepsia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidentes por Quedas , Apatia , Afasia/fisiopatologia , Afasia/terapia , Demência/psicologia , Demência/terapia , Epilepsia/fisiopatologia , Epilepsia/terapia , Pesquisas sobre Serviços de Saúde , Humanos , Japão/epidemiologia , Saúde Mental , Neurologistas , Neurocirurgiões , Doenças Retais/epidemiologia , Especialização , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Doenças da Bexiga Urinária/epidemiologia
7.
J Neurol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594451

RESUMO

OBJECTIVE: Patients with intracranial hemorrhages (ICH) after mechanical thrombectomy (MT) may have a higher risk of early recurrent embolism (ERE) because of delayed initiation of anticoagulants. We assessed the rate of ischemic events in the early period after MT and the association with post-MT ICH. METHODS: Patients who underwent MT in our institute were retrospectively reviewed. ERE was defined as recurrent ischemic stroke and systemic embolism within 14 days after MT. The association between ERE and parenchymal hematoma (PH) was assessed. Multivariable regression analysis and inverse probability of treatment weighting was used to adjust for differences in baseline characteristics between patients with and without PH. RESULTS: A total of 307 patients (median age, 78 years; female, 47%; median baseline National Institutes of Health Stroke Scale score, 19) were included. ERE was observed in 12 of 307 patients (8 strokes, 4 systemic embolisms; 3.9%). Median time from MT to ERE was 6.5 days (IQR, 3-8 days). PH occurred in 21 patients (6.8%). Median time from MT to initiating oral anticoagulants was longer in patients with PH (8 days) than in those without (3 days) (p < 0.01). In both unweighted and weighted multivariable analysis, PH was significantly associated with an increased risk of ERE (unweighted odds ratio, 10.60; 95% CI, 2.66-42.23; weighted odds ratio, 12.34; 95% CI, 2.49-61.07). CONCLUSIONS: ERE occurred in about 4% of patients after MT. PH after MT was associated with delayed initiation of oral anticoagulants and an increased risk of recurrent ischemic events. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02251665.

8.
BMC Neurol ; 21(1): 32, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482763

RESUMO

BACKGROUND: Internal carotid artery (ICA) stenosis has been recently reported to cause hemichorea, mainly in East Asia. The East Asian-specific p.R4810K variant of RNF213, a susceptibility gene for moyamoya disease (MMD), accounts for up to 25% of sporadic ischemic stroke with ICA stenosis cases in East Asia. However, as RNF213-related vasculopathy does not meet the diagnostic criteria for MMD, the creation of a new disease category has been suggested. Here, we report the first case of hemichorea in RNF213-related vasculopathy. CASE PRESENTATION: An 81-year-old woman was admitted to our hospital with choreic movements in the periphery of the right extremities at rest. Though head magnetic resonance imaging showed no fresh or old cerebral infarction, 123I-iodoamphetamine-single photon emission computed tomography showed cerebral blood flow of < 80% in the anterior territory of the left middle cerebral artery (MCA) in a resting state and cerebrovascular reactivity of < 10% in the broader area supplied by the left MCA after acetazolamide challenge. Head magnetic resonance angiography and digital subtraction angiography revealed left ICA C1 portion stenosis with compromised collateral vessels. Involuntary movements resolved with haloperidol administration within 3 days, without apparent recurrence from continuation of the medication for a year. Genetic testing revealed the presence of the heterozygous RNF213 p.R4810K variant. CONCLUSIONS: Chorea is thought to be caused by damage to circuitry connecting the basal ganglia with the cerebral cortex, as found in cases of MMD, which possess aberrant vessels in the basal ganglia. However, aberrant vessels and cerebral infarctions were not observed in the basal ganglia in the current case, decreasing the likelihood of a role in chorea. Alternatively, as RNF213 regulates vascular endothelial function and angiogenesis, dysregulation may impair the neurovascular unit and damage basal ganglia circuitry, contributing to the development of chorea. This case may renew interest in the concept of RNF213-related vasculopathy and the pathophysiological mechanisms behind chorea in ICA stenosis.


Assuntos
Adenosina Trifosfatases/genética , Estenose das Carótidas/complicações , Estenose das Carótidas/genética , Coreia/etiologia , Predisposição Genética para Doença/genética , Ubiquitina-Proteína Ligases/genética , Idoso de 80 Anos ou mais , Feminino , Humanos
9.
Sci Rep ; 11(1): 305, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431996

RESUMO

We investigated the potential of mid-regional pro-adrenomedullin (MR-proADM) for use as a novel biomarker for arterial stiffness as the criterion for vascular failure and cardiometabolic disease (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome) compared with high-sensitivity C-reactive protein (hsCRP). Overall, 2169 individuals (702 men and 1467 women) were enrolled. Multiple regression analysis was performed to assess the association of MR-proADM and hsCRP with brachial-ankle pulse wave velocity (baPWV), adjusting for other variables. The diagnostic performance (accuracy) of MR-proADM with regard to the index of vascular failure was tested with the help of receiver operating characteristic curve analysis in the models. MR-proADM was significantly higher in participants with vascular failure, as defined by baPWV and/or its risk factors (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome), than in control groups. Independent of cardiovascular risk factors (age, drinking, smoking, body mass index, systolic blood pressure, lipid and glycol metabolism), MR-proADM was significantly associated with baPWV, and MR-proADM showed higher areas under the curve of baPWV than hsCRP showed. MR-proADM is more suitable for the diagnosis of higher arterial stiffness as the criterion for vascular failure than hsCRP. Because vascular assessment is important to mitigate the most significant modifiable cardiovascular risk factors, MR-proADM may be useful as a novel biomarker on routine blood examination.

10.
Eur J Neurol ; 28(5): 1479-1489, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33370497

RESUMO

BACKGROUND AND PURPOSE: Various blood biomarkers reflecting brain amyloid-ß (Aß) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort. METHODS: Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) Aß40, Aß42, Aß42/Aß40 and the amplified plasmonic exosome (APEX) Aß42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aß+) participants. RESULTS: Compared to Simoa biomarkers, APEX-Aß42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre-screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX-Aß42 and 48.6% for Simoa-Aß42/Aß40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-Aß42 pre-screening does not increase the required number of initial participants. CONCLUSIONS: With its high diagnostic performance, APEX is an ideal candidate for Aß+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aß+ participants whilst halving recruitment costs.

11.
Stroke ; : STROKEAHA120030848, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33297866

RESUMO

BACKGROUND AND PURPOSE: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. METHODS: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. RESULTS: The median DWI-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI (P=0.026) and core volume (P=0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33-30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87-43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients. CONCLUSIONS: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr; Unique Identifier: UMIN000011630.

12.
J Neurointerv Surg ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33323502

RESUMO

BACKGROUND: We aimed to identify the large ischemic core (LIC) volume ranges in acute ischemic stroke patients that can benefit from mechanical thrombectomy (MT). METHODS: Consecutive patients within 24 hours of onset of anterior circulation ischemic stroke with large vessel occlusion and ischemic core volumes of 70-300 mL were included from our single-center prospective database from March 2014 to December 2019. Subjects were divided into three groups by baseline ischemic core volume (A: 70-100 mL; B: 101-130 mL; C: >130 mL). We compared modified Rankin Scale (mRS) score 0-2 at 3 months and parenchymal hematoma between patients receiving MT and standard medical treatment (SMT), and determined clinically treatable core volume ranges for MT. RESULTS: Of 157 patients (86 women; median age, 81 years; median ischemic core volume, 123 mL), 49 patients underwent MT. In Group A (n=52), MT patients (n=31) showed a higher proportion of mRS 0-2 at 3 months (52% vs 5%, P<0.05) versus SMT, respectively. Group B (n=36) MT patients (n=14) also had a higher proportion of mRS 0-2 at 3 months (29% vs 9%, P=0.13) versus SMT, respectively. In Group C (n=69), only four patients received MT. The 95% confidence intervals for the probability of mRS 0-2 at 3 months in patients with MT (n=49) versus SMT (n=108) intersected at 120-130 mL. CONCLUSIONS: Ischemic core volumes between 70 and 100 mL may benefit from MT. The treatable upper core limit is approximately 120 mL in selected patients with LIC of 70-300 mL.

13.
Neurology ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219136

RESUMO

OBJECTIVE: To compare the impact of intensive blood pressure (BP) lowering right after intracerebral hemorrhage (ICH) on clinical and hematoma outcomes among patients from different geographic locations, we performed a prespecified sub-analysis of the randomized, multi-national, two-group, open-label trial to determine the efficacy of rapidly lowering BP in hyperacute ICH (ATACH-2), involving 537 patients from East Asia and 463 recruited outside of Asia. METHODS: Eligible patients were randomly assigned to a systolic BP (SBP) target of 110-139 mmHg (intensive treatment) or 140-179 mmHg (standard treatment). Pre-defined outcomes were: poor functional outcome (modified Rankin Scale score of 4-6 at 90 days), death within 90 days, hematoma expansion at 24 hours; and cardio-renal adverse events within 7 days. RESULTS: Poor functional outcomes (32.0% versus 45.9%), death (1.9% versus 13.3%), and cardio-renal adverse events (3.9% versus 11.2%) occurred significantly less in patients from Asia than those outside of Asia. The treatment-by-cohort interaction was not significant for any outcomes. Only patients from Asia showed a lower incidence of hematoma expansion with intensive treatment (adjusted RR 0.56, 95% CI 0.38-0.83). Both Asian (3.53, 1.28-9.64) and non-Asian cohorts (1.71, 1.00-2.93) showed a higher incidence of cardio-renal adverse events with intensive treatment. CONCLUSIONS: Poor functional outcomes and death 90 days after ICH were less common in patients from East Asia than those outside of Asia. Hematoma expansion, a potential predictor for poor clinical outcome, was attenuated by intensive BP lowering only in the Asian cohort. CLINICALTRIALSGOV IDENTIFIER: NCT01176565. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, for patients from East Asia with intracerebral hemorrhage, intensive blood pressure lowering significantly reduces the risk of hematoma expansion.

14.
Front Aging Neurosci ; 12: 538456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240073

RESUMO

Cerebral amyloid angiopathy (CAA) is characterised by the progressive accumulation of ß-amyloid (Aß) in the walls of cerebral capillaries and arteries representing a major cause of haemorrhagic stroke including lobar intracerebral haemorrhage (ICH) and convexity subarachnoid haemorrhage (SAH). Haemorrhaging from CAA predominantly involves smaller arteries rather than arterial aneurysm. Restricted bleeding into the subarachnoid space in CAA results in asymptomatic or mild symptomatic SAH. Herein, we present an autopsied case of massive SAH related to CAA. An 89-year-old male with a history of mild Alzheimer's disease (AD) and advanced pancreatic cancer with liver metastasis developed sudden onset of coma. Head CT illustrated ICH located in the right frontal lobe and right insula, as well as SAH bilaterally spreading from the basal cistern to the Sylvian fissure, with hydrocephalus and brain herniation. He died about 24 h after onset and the post-mortem examination showed no evidence of arterial aneurysm. The substantial accumulation of Aß in the vessels around the haemorrhagic lesions led to the diagnosis of ICH related to CAA and secondary SAH, which may have been aggravated by old age and malignancy. This case suggests that CAA can cause severe SAH resembling aneurysmal origin and thus may be overlooked when complicated by atypical cerebral haemorrhage.

15.
Stroke ; 51(12): 3632-3639, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33148146

RESUMO

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) are associated with stroke and cognitive impairment. We previously reported a high prevalence of CMB in people with Streptococcus mutans expressing Cnm, a collagen-binding protein in the oral cavity. S. mutans is a major pathogen responsible for dental caries. Repeated challenge with S. mutans harboring the cnm gene encoding Cnm induced cerebral bleeding in stroke-prone spontaneously hypertensive rats. The purpose of this longitudinal study is to examine the relationship of cnm-positive S. mutans to the development of CMB. METHODS: We retrospectively investigated patients with stroke receiving oral microbiological examination and head 3T magnetic resonance imaging evaluations twice in the period 2014 to 2019, allowing >180-day interval. Patients with cnm-positive S. mutans were compared with those without. Quasi-Poisson regression models were used to explore associations between cnm-positive S. mutans and the increase in number of CMB between the 2 magnetic resonance imaging scans. RESULTS: A total of 111 patients were identified; 21 (19%) with cnm-positive S. mutans and 90 (81%) without. Clinical history, including blood pressure and the use of antithrombotic agents, were comparable between the 2 groups. New CMB were more commonly observed in patients with cnm-positive S. mutans (52% versus 23%; P=0.008). The incidence of CMB was significantly higher in the group with cnm-positive S. mutans, especially in deep areas, (incidence rate ratios [95% CI], 5.1 [1.9-13.6] for CMB in any brain region; 15.0 [5.4-42.0] for deep CMB), which persisted after adjusting for age, sex, hypertension, and renal impairment (4.7 [1.8-11.9] for CMB in any brain region; 13.9 [4.3-44.5] for deep CMB). CONCLUSIONS: This study demonstrates that cnm-positive S. mutans is associated with an increased incidence of CMB. Treatment for cnm-positive S. mutans infection may be a novel microbiota-based therapeutic approach for stroke and cognitive impairment.

16.
Neurobiol Aging ; 97: 33-40, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130454

RESUMO

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary cerebral small vessel disease. Previous neuroimaging studies have suggested loss of hippocampal volume is a pathway for cognitive impairment in CADASIL. We used unbiased stereological methods to estimate SMI32-positive and total numbers and volumes of neurons in the hippocampal formation of 12 patients with CADASIL and similar age controls (young controls) and older controls. We found densities of SMI32-positive neurons in the entorhinal cortex, layer V, and cornu ammonis CA2 regions were reduced by 26%-50% in patients with CADASIL compared with young controls (p < 0.01), with a decreasing trend observed in older controls in the order of young controls> older controls ≥ CADASIL. These changes were not explained by any hippocampal infarct or vascular pathology or glial changes. Our results suggest notable loss of subsets of projection neurons within the hippocampal formation that may contribute to certain memory deficits in CADASIL, which is purely a vascular disease. It is likely that the severe arteriopathy leads to white matter damage which disconnects cortico-cortical and subcortical-cortical networks including the hippocampal formation.

17.
eNeurologicalSci ; 21: 100283, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33102822

RESUMO

A 51-year-old man with type 2 diabetes mellitus was admitted with a 2-month history of repeated episodes of transient aphasia and right hemiparesis after food intake. His blood pressure (BP) fell when the neurological deficits developed. The fall in BP after each meal was confirmed by 24-h ambulatory blood pressure monitoring (ABPM), which established the diagnosis of postprandial hypotension (PPH). Diffusion-weighted magnetic resonance imaging of the brain showed multiple high-intensity lesions at the borderzone between the anterior and middle cerebral artery (MCA) territories in the left hemisphere. Digital subtraction angiography showed tapered occlusion at the origin of the left internal carotid artery (ICA). Despite sufficient antiplatelet therapy and medication for PPH, the transient symptoms remained. Positron emission tomography scanning using H2 15O showed decreased cerebral blood flow with increased oxygen extraction fraction in the left MCA territory. As the symptomatic left ICA occlusion was intractable, an extracranial-intracranial (EC-IC) bypass surgery was conducted without any perioperative complications. Although PPH remained, cerebrovascular ischemic events including repeated transient ischemic attack disappeared for 2 months after surgery. The coincidence of stroke with ABPM-proved transient hypotension suggested that the brain infarcts were caused by hemodynamic changes related to PPH co-existent with the chronic left ICA occlusion. ABPM is useful in evaluating hemodynamic infarcts associated with BP fluctuation, and should be considered for patients with chronic ICA occlusion. In addition, EC-IC bypass may be a treatment option for symptomatic chronic ICA occlusion due to PPH.

18.
Alzheimers Dement (N Y) ; 6(1): e12089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117881

RESUMO

Introduction: Equol, a metabolite of a soy isoflavone transformed by the gut microbiome, is anti-oxidant and anti-amyloidogenic. We assessed the associations of equol with white matter lesion normalized to total brain volume (WML%) and amyloid beta (Aß) deposition. Methods: From 2016 to 2018, 91 cognitively normal elderly Japanese aged 75 to 89 underwent brain magnetic resonance imaging and positron emission tomography using 11C-Pittsburgh compound-B. Serum equol was measured using stored samples from 2008 to 2012. Equol producers were defined as individuals with serum levels >0. Producers were further divided into high (> the median) and low (≤ the median) producers. Results: The median (interquartile range) WML% was 1.10 (0.59 to 1.61); 24.2% were Aß positive, and 51% were equol producers. Equol-producing status (non-producers, low and high) was significantly inversely associated with WML%: 1.19, 0.89, and 0.58, respectively (trend P < .01). Equol-producing status was not associated with Aß status. Discussion: A randomized-controlled trial of equol targeting WML volume is warranted.

19.
J Stroke Cerebrovasc Dis ; 29(11): 105256, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066937

RESUMO

BACKGROUND AND PURPOSE: We hypothesized that the relationships between treatments and outcomes in acute basilar artery occlusion (BAO) are different, depending on the severity of initial neurological deficits. METHODS: Of 2420 ischemic stroke patients with large vessel occlusion in a prospective, multicenter registry in Japan, patients with acute BAO were enrolled. Subjects were divided into two severity groups according to the baseline NIH Stroke Scale score: severe (≥10) and mild (<10) groups. The primary effectiveness outcome was favorable outcome, defined as modified Rankin Scale score 0-3 at 3 months. Safety outcomes included any intracranial hemorrhage (ICH) within 72 h. Outcomes in each group were compared between patients who received endovascular therapy (EVT) and those with standard medical treatment (SMT). RESULTS: In this study, 167 patients (52 female; median age 75 years) were analyzed. The favorable outcome was seen in 93 patients (56%) overall. In the severe group (n = 128), the proportion of favorable outcome was higher in patients who received EVT (60/111, 54%) than those with SMT (2/17, 12%, P < 0.01). In the mild group (n = 39), the rates of favorable outcome were comparable between the EVT (13/18, 72%) and SMT patients (18/21, 86%, P = 0.43). No significant differences in the rates of any ICH were seen among any groups. CONCLUSIONS: In acute BAO stroke with severe neurological deficit, independent ambulation was more frequently seen in patients who received EVT than those with SMT. Patients with mild neurological deficits showed similar rates of independent ambulation between the two treatment selections.

20.
Diabetes Ther ; 11(11): 2729-2737, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889699

RESUMO

INTRODUCTION: Although the risk of dementia among patients with type 2 diabetes mellitus (T2DM) is double that of those without T2DM, the mechanism remains to be elucidated and the glycemic goal to prevent progression of cognitive impairment is unclear. Results from cross-sectional studies suggest that glucose fluctuations are associated with impairment of cognitive function among T2DM patients. Therefore, the aim of the longitudinal study described here is to evaluate the relationships between glucose fluctuation indexes assessed by continuous glucose monitoring (CGM) and cognitive function among elderly patients with T2DM. METHODS: This will be a prospective, single-center, 2-year longitudinal study in which a total of 100 elderly patients with T2DM showing mild cognitive impairment (MCI) will be enrolled. Glucose fluctuations, assessed using the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories), and results of cognitive tests, namely the Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale (ADAS), will be evaluated at baseline, 1-year visit and 2-year visit. The primary endpoint is the relationships between indexes of glucose fluctuation and change in MoCA and ADAS scores. Secondary endpoints are the relationships between the indexes of glucose fluctuation or cognitive scores and the following: indexes representing intracranial lesions obtained by magnetic resonance imaging and angiography of the head; Geriatric Depression Scale score; Apathy Scale score; carotid intima-media thickness assessed by echography; inflammatory markers; fasting glucose; glycated hemoglobin; blood pressure; and the development of cardiovascular and renal events. PLANNED OUTCOMES: The current study is scheduled for completion in June 2022. The results could lead to the elucidation of novel glycemic goals to prevent the progression of cognitive impairment and/or of relationships between glucose fluctuations and cognitive function among T2DM patients. The findings of the study will be reported in publications and conference presentations. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000038546).

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