Small vessel platelet thrombosis in the peripheral nerves in POEMS syndrome.

INTRODUCTION/AIMS: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M-protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. METHODS: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. RESULTS: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. DISCUSSION: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin-12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder.

Cilostazol Addition to Aspirin could not Reduce the Neurological Deterioration in TOAST Subtypes: ADS Post-Hoc Analysis.

BACKGROUND: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. METHODS: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). RESULTS: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030). CONCLUSIONS: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

Neisseria macacae bacteremia: report of two cases with a literature review.

BACKGROUND: Neisseria macacae was discovered in the oral cavity of monkeys in 1983. In humans, it has been isolated from the upper respiratory tract of neutropenic patients. However, only two cases of N. macacae bacteremia have been reported in a 65-year-old man with infective endocarditis and a 5-month-old child with fever and petechiae. There are no reports of infections in cancer patients. Here, we present two cases of N. macacae bacteremia in cancer patients. CASE PRESENTATION: In the first case, a 42-year-old woman who underwent ovarian cancer surgery presented with duodenal invasion associated with multiple lymph node metastasis. N. macacae was isolated from her blood culture and identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). In the second case, a 69-year-old woman with a long-standing history of esophagogastric junction cancer presented with fever. She had stage IVB cancer with lung, bone, and multiple lymph node metastasis. The last chemotherapy was administered 5 weeks before N. macacae was detected using MALDI-TOF MS and nitrate test negative. In both cases, transthoracic echography showed no vegetation. Antibiotics were administered for 14 and 13 days in the first and second cases, respectively. In both cases, fever alleviated on day 4 of antibiotic administration. Both patients were discharged after their conditions improved. CONCLUSIONS: This, to our knowledge, is the first report of N. macacae bacteremia in cancer patients. Both patients, mucosal damage was observed in the upper gastrointestinal tract. Therefore, exclusion diagnosis suggested that bacteremia invasion was caused by mucosal rupture in both cases. Both cases responded well to treatment with ß-lactam antibiotics and improved after 2 weeks. Modifying the treatment based on the source of the infection may shorten the treatment period. Therefore, further research on N. macacae bacteremia is necessary. Immunocompromised patients such as those with cancer are susceptible to mucosal damage by unusual bacterial species such as N. macacae despite not having contact with monkeys.

Clinical features of Clostridium bacteremia in cancer patients: A case series review.

Clostridium bacteremia is a well-known cause of infection in patients with gastrointestinal lesions. However, the clinical characteristics of this infection in cancer patients are unclear. We retrospectively reviewed cases of blood cultures positive for Clostridium species between March 1, 2004 and May 30, 2018 at the Shizuoka Cancer Center Hospital. Medical records of 40 patients who met the study criteria were reviewed for age, gender, underlying disease, history of disease, blood culture results, laboratory test results, and radiographic data. The common sources of Clostridium species in these patients were hepatobiliary tract infection and liver abscess (13/40; 32.5%) and bacteremia/enteritis due to gastrointestinal tumor (13/40; 32.5%). All patients had malignancies, with the most common being colorectal cancer (n = 9) followed by pancreatic cancer (n = 8) and gastric cancer (n = 6). The most common species isolated was C. perfringens followed by C. ramnosum. Twenty-five patients (62.5%) had polymicrobial bacteremia with the following organisms isolated from concurrent blood cultures: Escherichia coli (n = 8) and Klebsiella spp. (n = 7). Of these bacteremia cases, 37 had digestive organ lesions such as gastrointestinal malignancy, peritoneal dissemination, or intestinal infiltration. Seventeen patients died, resulting in an overall mortality rate of 42.5% at 30 days. Common cases of Clostridium bacteremia were derived from gastrointestinal lesions, and because Clostridium bacteremia is observed regardless of species, it should be considered necessary to examine gastrointestinal lesions.

Infectious disease specialist consultations in a Japanese cancer center: a retrospective review of 776 cases.

BACKGROUND: Little is known about the impact of infectious disease (ID) consultations on the management of patients with cancer. This study aimed to describe the consultation services provided by ID specialists to all departments in a comprehensive cancer center in Japan. METHODS: We conducted a retrospective review of ID consultations with adult patients at a comprehensive cancer center in Japan from April 2017 to March 2018. RESULTS: During the study period, 776 patients with cancer had an ID consultation. Of these, 414 (53.4%) were hospital inpatients. Reasons for the ID consultation comprised clinical management (n = 481, 62.0%), immunization (n = 272, 35.1%), and infection control (n = 23, 3.0%). Of the 474 ID consultations for diagnostic purposes, the most frequent condition was fever or elevated inflammatory markers of unknown origin (n = 125, 26.4%). The most frequent diagnoses after the diagnostic ID consultation were hepatobiliary infections (n = 97, 22.4%), respiratory infections (n = 89, 20.618.8%), and intra-abdominal infections (n = 71, 16.4%). The commonest reasons for immunization consultations were to prevent seasonal influenza (n = 193, 71.0%) and post-splenectomy vaccination (n = 58, 21.3%). The commonest reasons for infection control consultations were suspected tuberculosis or contact with tuberculosis (n = 11, 47.8%) and herpes zoster infection (shingles) (n = 7, 30.4%). CONCLUSIONS: ID specialists play an important role in the clinical management of patients with cancer. ID physicians who work in cancer centers need to be specialized in treating IDs, diagnosing the causes of fevers of unknown origin, and controlling infection.

Association of CYP2C19 Polymorphisms With Clopidogrel Reactivity and Clinical Outcomes in Chronic Ischemic Stroke.

BACKGROUND: CYP2C19variants are associated with the antiplatelet effects of clopidogrel against recurrent cardiovascular events. However, it remains unknown whether the elapsed time from stroke onset affects the relationship between the genetic variants and such events. To address this, we conducted a prospective cohort study to determine the effect ofCYP2C19variants on clinical outcomes in the chronic phase.Methods and Results:In total, 518 Japanese non-acute stroke patients treated with clopidogrel were registered at 14 institutions. Patients were classified into 3 clopidogrel-metabolizing groups according toCYP2C19genotype: extensive metabolizer (EM:*1/*1), intermediate metabolizer (IM:*1/*2or*1/*3), and poor metabolizer (PM:*2/*2,*2/*3, or*3/*3). Antiplatelet effects of clopidogrel were assessed by adenosine diphosphate (ADP)-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. The endpoint was composite cerebrocardiovascular events (CVEs). In 501 successfully followed-up patients, the median time from index stroke to enrollment was 181 days. There were 28 cardiovascular and 2 major bleeding events. There were no significant differences in the rates of cardiovascular events among the groups. CONCLUSIONS: Despite associations betweenCYP2C19variants and on-clopidogrel platelet reactivity, there was no significant difference in rates of CVEs in the chronic stroke phase among the 3 clopidogrel-metabolizing groups ofCYP2C19variants.

High Morning and Bedtime Home Blood Pressures Strongly Predict for Post-Stroke Cognitive Impairment.

BACKGROUND: Hypertension may be the most modifiable risk factor for post-stroke cognitive impairment (PSCI). We investigated how home blood pressure (HBP) can predict PSCI as well as stroke recurrence. METHODS: We studied 249 consecutive patients with noncardioembolic minor ischemic stroke including single lacunar infarct (sLI), multiple lacunae (mLI), and atherothrombotic infarction, which were tracked at our outpatient clinic. HBP was measured in the early morning (m-HBP) and just before going to bed (b-HBP). HBP categories based on systolic blood pressure were created as follows: HB1, both m-HBP and b-HBP less than 135 (mmHg); HB2, m-HBP less than or equal to135 and b-HBP less than 135; HB3, m-HBP less than 135 and b-HBP less than or equal to 135; HB4, both m-HBP and b-HBP less than or equal to 135. After 4.1 years of tracking, the patients were divided into 4 groups: Group 1, good outcome (n = 188); Group 2, the development of silent infarcts (n = 16); Group 3, the development of PSCI (n = 33); and Group 4, stroke recurrence (n = 15). RESULTS: HB2 and HB4 (versus HB1) (hazard ratio [HR]: 6.5, P = .0068 and HR: 9.5, P = .0008, respectively) and mLI (versus sLI) (HR: 4.0, P = .021) were independently associated with Group 2. HB3 and HB4 (HR: 4.2, P = .037; HR: 5.4, P < .0001) and mLI (HR: 6.4, P < .0001) were significantly associated with Group 3. HB4 (HR: 8.1, P = .0002) and mLI (HR: 10.2, P = .0003) were significantly associated with Group 4. Clinic blood pressure (BP) was not significantly associated with any adverse groups. CONCLUSIONS: High HBP and mLI were strongly associated with PSCI as well as stroke recurrence. BP should be monitored based on HBP, especially bedtime HBP, for the prevention of PSCI.

Analysis of Factors Associated with Progression and Long-Term Outcomes of Penetrating Artery Territory Infarction: A Retrospective Study.

BACKGROUND: Patients with penetrating artery territory infarction occasionally show progressive motor deficits during the acute stage with poor prognosis. Predictive indices or medical therapies for suppressing the symptomatic progression (SP) of penetrating artery infarction have not been established. In this study, we investigated SP-related clinical factors and functional outcomes, specifically improvement 3 months post ictus in patients with penetrating artery infarction. METHODS: We retrospectively examined acute stroke patients with penetrating artery infarction admitted at 7 collaborative hospitals. SP was defined as an increase by 1 point or higher in the National Institutes of Health Stroke Scale score. Functional improvement was assessed based on the modified Rankin Scale at 3 months. The influence of factors, such as patient characteristics, clinical data, medical treatment during the acute stage and on SP, and functional improvement was statistically analyzed. RESULTS: Four hundred eighty-eight patients (310 men; mean age, 70 years) were examined. Sixty-eight patients (14%) exhibited SP. Multivariate logistic regression analysis revealed that higher hemoglobin A1c (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.10-1.55), body mass index (BMI; OR, .85; 95% CI, .77-.94), and systolic blood pressure on admission (OR, 1.63; 95% CI, 1.19-2.25) were independent predictors of SP in penetrating artery infarction. Dual antiplatelet therapy (DAPT; OR, 3.48; 95% CI, 1.52-8.38) independently influenced functional improvement. CONCLUSIONS: Initial high blood pressure, diabetes, and low BMI on admission were associated with early progression of penetrating artery infarction. DAPT during the acute stage may contribute to functional improvement.

The Impact of Diagnosing Branch Atheromatous Disease for Predicting Prognosis.

BACKGROUND: We had reported that, in the acute phase of the brain penetrating artery infarction, patients with branch atheromatous disease (BAD) tended to be worsened compared with the lacunar infarction (LI). Because no prospective study has been reported, we composed a multicenter study (Japan Branch Atheromatous Disease [J-BAD] Registry) in which patients of penetrating artery infarction were prospectively enrolled for exploring the clinical features of BAD. METHODS: From the associated 9 hospitals, acute ischemic stroke patients were asked to be enrolled in the J-BAD Registry and classified into the lenticulostriate arterial (LSA) infarction (n = 124) and the pontine penetrating arterial (PPA) infarction (n = 42) groups. The clinical courses and the repeated magnetic resonance imaging findings were investigated. RESULTS: Neurologic worsening was observed at a significantly higher rate in BAD compared with the LI patients in both the LSA and PPA groups (P < .01, 45.1% versus 22.6% and 46.7% versus 0%, respectively). In the LSA group, the enlargement of the ischemic lesion was significantly more frequent in BAD compared with the LI patients (P < .01, 66.2% and 34.0%, respectively). There was a significant relation between the enlargement of the lesion and the worsening of neurologic deficits (P < .001). Moreover, the clinical features, which predict the lesion enlargement, were BAD and older age. CONCLUSIONS: LSA infarction of BAD diagnosis or older age patients might show an increase of lesion size and a tendency of neurologic worsening. It could be important to discriminate BAD from other ischemic stroke subtypes, in regard to the prediction of prognosis.

Subsequent vascular events after ischemic stroke: the Japan Statin Treatment Against Recurrent Stroke-Longitudinal.

BACKGROUND: We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. METHODS: This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. RESULTS: A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). CONCLUSIONS: This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.

The relationship between neurological worsening and lesion patterns in patients with acute middle cerebral artery stenosis.

BACKGROUND: Intracranial atherosclerotic disease is one of the most common causes of ischemic stroke especially in Asians, Hispanics and blacks. Although middle cerebral artery (MCA) stenosis is increasingly being recognized with the advent of magnetic resonance angiography (MRA) or transcranial Doppler ultrasonography, few studies have focused on acute neurological worsening (NW) in patients with MCA stenosis. We investigated the relationship between NW and lesion patterns detected by diffusion-weighted imaging (DWI). METHODS: We studied 44 consecutive patients out of a total of 2,863 consecutive patients who had symptomatic lesions in the territory of the MCA and in whom MRA and/or conventional angiography showed isolated MCA stenosis ≥50% in the MCA trunk. Acute DWI lesion patterns were classified as follows: (1) pial artery territory infarcts (PAI); (2) small cortical and/or subcortical infarcts (SCS); (3) deep penetrating artery territory infarcts (DPI); (4) cortical border zone infarcts (CBZ), and (5) internal border zone infarcts (IBZ). NW was defined as worsening by ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) during the first 7 days. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months after stroke onset. Poor outcome was defined as ≥3 on the mRS. The severity of MCA stenosis on MRA was further categorized as 50-75% (moderate) and >75% or focal signal loss with the presence of distal MCA signal (severe). RESULTS: There were 14 patients (31.8%) who showed NW and 16 patients (36.3%) who showed poor outcomes. Nine of the 14 patients with NW showed poor outcomes (64.2%). The most frequent lesions in the present study were SCS (n = 16, 36.3%), followed by IBZ (n = 12, 27.2%) and DPI (n = 11, 25.0%). Prevalence of IBZ was significantly higher in the group with NW compared to that without NW (p = 0.0081), while the prevalence of SCS, DPI, PAI and CBZ did not differ between the two groups. Logistic regression analysis showed significantly high age- and sex-adjusted odds ratios (ORs) for NW only for IBZ (OR 10.9, p = 0.0051). The degree of stenosis did not correlate with NW and lesion patterns. CONCLUSIONS: Only IBZ among various lesion patterns correlated strongly with NW. IBZ are considered to be more associated with hemodynamic compromise, while embolic pathogeneses contribute more to CBZ or SCS. Early interventional medical treatments such as thrombolytic or anti-platelet therapy or stenting should be considered in cases of IBZ in MCA stenosis.

Clinical and Radiological Features of Stroke Patients with Poor Outcomes Who Do Not Receive Intravenous Thrombolysis because of Mild Symptoms.

BACKGROUND AND AIMS: A substantial proportion of patients who did not receive intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA), solely because of mild symptoms, can show poor outcome. The aim of our study was to analyze clinical and radiological features of the patients. METHODS: We enrolled 72 patients between 2007 and 2009 who presented to our hospital within 3 h after stroke onset and who did not receive rtPA therapy solely because of mild symptoms (NIHSS score of ≤ 4 at rtPA decision), and examined detailed characteristics of patients with poor outcomes. Poor outcome was defined as a modified Rankin Scale score of ≥ 2 at 3 months after the stroke. RESULTS: Eleven of 72 patients (15%) had poor outcomes. Major vessel occlusion was observed in 7 of the 11 patients. Neurological deterioration after admission was main reason for poor outcome. Infarct expansion in 6 patients (2 large artery diseases and 4 small vessel diseases) and distal embolism by clot migration in 3 patients led to neurological deterioration. CONCLUSIONS: Clinical and radiological features of mild stroke patients with poor outcomes, who did not receive rtPA therapy, were identified. In such patients, intravenous thrombolysis may be justified.

Intensive blood pressure-lowering treatment in patients with acute lacunar infarction.

BACKGROUND: The optimal management of high blood pressure (BP) during the acute stage of stroke has yet to be established. To test the extent to which BP can be lowered without causing adverse effects and to determine the safety or efficacy of administration of antihypertensive agents in acute ischemic stroke, we performed ambulatory BP monitoring (ABPM) before and after administration of angiotensin receptor blockers (ARBs) with and without diuretics to monitor the ABPM profile after acute lacunar infarction. Patients with lacunar infarcts are presumed to be less vulnerable to reduced cerebral perfusion pressure in the ischemic tissue because of BP lowering. METHODS: We prospectively performed ABPM during the acute stage and around 3 weeks after ictus for 59 patients with lacunar infarction. As a historical control group, we selected 60 consecutive patients with acute lacunar infarction who were admitted during the period of 1 year before the present study and treated according to the guidelines. RESULTS: Baseline data, prevalence of progressive motor deficits, and modified Rankin Scale scores 3 months after ictus were not significantly different between both groups. ARB with or without diuretics lowered 24-hour systolic BP and diastolic BP by 27.8 and 12.7 mm Hg, daytime systolic BP and diastolic BP by 26.8 and 12.0 mm Hg, and nighttime systolic BP and diastolic BP by 30.2 and 12.0 mm Hg. The incidence of dippers tended to increase in the second measurement from 11 (18.6%) to 20 (33.8%; P=.093). CONCLUSIONS: Considerable reduction in 24-hour BP levels was attained around day 21. The limit of BP level to which BP can be safely lowered appears to be lower than that was previously considered.

Intensive or standard blood pressure control in patients with a history of ischemic stroke: RESPECT post hoc analysis.

The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7-134.1/76.9-78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0-127.4/73.5-74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke.

A combined treatment for acute larger lacunar-type infarction.

Larger lacunar-type infarcts (LLIs), presumably caused by occlusion at the orifices or proximal portions of larger-caliber penetrating arteries by atheromatous plaque, are frequently associated with progressive motor deficits (PMD) and lead to poor functional outcome. This study was conducted to examine the efficacy of a combined treatment to prevent PMD or improve the functional outcome in patients with LLI. A total of 218 consecutive patients with LLI and motor lacunar syndrome were enrolled, including 138 patients with infarcts in the territory of the lenticulostriate artery and anterior choroidal artery (supratentrial group) and 80 patients with infarcts in the territory of the anterior pontine artery (pontine group). The prevalence of PMD and functional outcome represented by modified Rankin Scale (mRS) score at 1 month after ictus were compared between groups treated with a combined treatment approach consisting of cilostazol and edaravone (n = 100) and a conventional treatment approach (n = 118). The efficacy of the combined treatment provided in 2005-2009 was compared with conventional treatment provided in 2001-2005. There was no significant difference in the prevalence of PMD between the 2 treatment groups. The combined treatment group had significantly more favorable outcomes compared with the conventional treatment group in the total population (P = .0078, Wilcoxon Mann-Whitney test) and in the pontine group (P = .0042). Logistic regression analysis showed that an initial National Institutes of Health Stroke Scale score <4, the absence of PMD, and the novel combined treatment approach were independently associated with favorable functional outcome. The novel combined treatment approach was safe and effective in improving functional outcome in acute LLI, but not effective in preventing PMD.

[Classification of etiologic subtypes for transient ischemic attacks: clinical significance of lacunar transient ischemic attack].

BACKGROUND: Lacunar transient ischemic attack (lacunar TIA) may have been underestimated because of diagnostic difficulties. The aim of our study was to classify TIAs by etiologic subtypes, especially using defined criteria for diagnosis of lacunar TIA and clarify clinical characteristics of lacunar TIA. METHOD: 105 TIA patients out of consecutive 1,244 patients with acute ischemic stroke admitted to our hospital between January 2007 and June 2010 were enrolled in the present study. TIA was defined as an acute focal neurological deficit lasting less than 24 hours, suspected to be of cerebrovascular origin regardless of ischemic lesions on MRI. TIAs were classified to 5 etiologic subtypes; (1) cardioembolic TIA, (2) atherothrombotic TIA, (3) lacunar TIA, (4) other etiologies, and (5) undetermined etiology and clinical characteristics in each subtype and the incidence of recurrent stroke after TIA were investigated. Lacunar TIA was diagnosed if the following criteria were fulfilled; (1) presence of lacunar infarct on MRI and/or the presence of unilateral dysfunction of at least two of three body parts (face, arm, leg) in the absence of cortical dysfunction presumed due to subcortical ischemia. (2) absence of cardiac sources of embolism and large artery atherosclerosis. RESULTS: In 105 patients with TIA, lacunar TIA was the most frequent etiology (31%) followed by cardioembolic TIA (27%), atherothrombotic TIA (19%), undetermined etiology (18%), and other etiologies (6%). In patients with lacunar TIA, history of repeated TIA was more frequent and systolic blood pressure on admission was higher significantly than in cardioembolic TIA. Six of 105 patients had experienced recurrent stroke after TIA during admission. Among these 6 patients, 3 patients were diagnosed as lacunar infarctions. CONCLUSIONS: Lacunar TIA was most common TIA subtype in the present study. It is critical to identify lacunar TIA on admission because some patients with lacunar TIAs experience early recurrent stroke.

Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine.

INTRODUCTION: Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework. AREAS COVERED: Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimer's disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimer's disease to date. EXPERT OPINION: With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.

Attack Interval Is the Key to the Likely Pathogenesis of Multiple Transient Ischemic Attacks.

INTRODUCTION: The aim of this study was to test the hypothesis that the attack interval of multiple transient ischemic attacks (TIAs) is correlated with the underlying pathogenesis of ischemia. METHODS: Patients with multiple TIAs, defined as 2 or more motor deficits within 7 days, were studied. The attack interval between the last 2 episodes was classified into 3 groups: 2 episodes within an hour (Hour group), over hours within a day (Day group), and over days within a week (Week group). Patients with a lacunar syndrome, no cortical lesions, and no embolic sources were recognized as having a small vessel disease (SVD) etiology for their multiple events. RESULTS: Of 312 TIA patients admitted over a 9-year period, 50 (37 males, 13 females, mean 67.6 years) had multiple TIAs. Twelve patients were classified as being within the Hour group, 23 within the Day group, and 15 within the Week group. Lacunar syndromes were observed in 30 (75%, 35%, and 67%), embolic sources were detected in 28 (25%, 65%, and 67%), and a high signal lesion on diffusion-weighted imaging was depicted in 30 (75%, 48%, and 67%) patients (18 cortical, 11 subcortical, and one cerebellar). Patients in the Hour group had a significantly higher prevalence of SVD etiology (75%) than those in the Day and Week groups (30%, p = 0.0165; 27%, p = 0.0213, respectively). Four patients had a subsequent stroke within 7 days. CONCLUSION: Attack intervals of multiple TIAs may be correlated with the underlying pathogenesis of ischemia. Two motor deficits within an hour are more likely to suggest a SVD etiology.

Microbleeds and clinical outcome in acute mild stroke patients treated with antiplatelet therapy: ADS post-hoc analysis.

BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.

[Cerebral deep vascular architectures and subcortical infarcts].

The lenticulostriate arteries (LSA) supply the lateral half of the head of the caudate nucleus, entire putamen, anterior limb, genu and the superior part of the internal capsule (IC) and a part of the corona radiata. The LSA consists with medial, intermediate and lateral branches. The medial branches perfuse the lateral segment of the globus pallidus, the head of the caudate nucleus and the anterior limb of the IC. The intermediate branches supply the anterior half of the LSA territory, while the lateral branches supply the posterior half. The anterior cerebral artery (ACA) perforators, predominantly Heubner's artery, perfuse the inferomedial part of the caudate head, the anteromedial part of putamen, the anterior part of the lateral segment of the globus pallidus and anterior limb of the internal capsule. Such territories can be represented by the anterior and ventral basal ganglions. The anterior choroidal artery (AChA) gives off three main groups of branches including the lateral branches that supply the medial temporal lobe, the medial branches that supply the cerebral peduncle and the superior branches that supply the internal capsule and the basal ganglia. The superior branches are further discriminated into proximal branches that supply the anterior one third of the posterior limb of internal capsule (PLIC) and the medial segment of the globus pallidus and distal branches that supply the posterior two-third of PLIC, retro-lenticular part of the internal capsule and the lateral thalamic nuclei. The superficial penetrating arteries, i.e. medullary arteries, arise from the cortical branches of the middle cerebral artery (MCA) and supply the deep white matter. Infarcts caused by the medullary artery occlusion are located in the centrum-semiovale and half of them were caused by embolic mechanism. The centrum-semiovale corresponds to cortical border-zone (BZ) while the corona radiate corresponds to internal BZ.