Tomoyuki Ohara

Takotsubo Cardiomyopathy in Acute Ischemic Stroke

Takotsubo cardiomyopathy, which is characterized by transient left ventricular apical ballooning, is a known complication of subarachnoid hemorrhage. The aim of this study was to identify the clinical characteristics of acute ischemic stroke patients who experienced development of takotsubo cardiomyopathy.

Evaluation of Factors Associated With Elevated Levels of Platelet-Derived Microparticles in the Acute Phase of Cerebral Infarction

Background: Platelet-derived microparticles (PDMPs) have attracted attention as blood coagulation-promoting, endothelial cell-activating factors. The objective of this study was to determine the parameters associated with elevated PDMP levels and examine their relationship with atherosclerotic lesions of main intracranial and extracranial arteries. Participants and Methods: Participants included a control group (C) of 61 patients with no apparent cerebral vascular lesions and 110 patients with acute-phase cerebral infarction, consisting of a small-vessel occlusion group (S) of 34 patients, a large-artery atherosclerosis group (L) of 41 patients, a cardioembolism group (CE) of 20 patients, and a stroke of undetermined etiology group (U) of 15 patients. Platelet-derived microparticle levels were measured using enzyme-linked immunosorbent assay (ELISA) at the time of admission, and the patients were reclassified into group CP (control level PDMPs), consisting of 70 patients with control PDMP levels, and group HP (high PDMPs), consisting of 40 patients with elevated PDMP levels. All patients underwent cranial magnetic resonance (MR) and carotid ultrasound examinations. Results: Platelet-derived microparticle levels were significantly higher in groups S and L than in group C (P < .01). Concomitant intima-media thickness (IMT; odds ratio [OR] = 1.29, P < .05) and concomitant intracranial stenosis (OR = 3.95, P < .01) were significantly correlated with elevated PDMP levels. Fibrinogen and high-sensitivity CRP levels were significantly higher in group HP than in group CP. Conclusion: Alterations in PDMP levels correlated with the presence of atherothrombotic lesions, and PDMP levels are expected to be useful as a clinical indicator, reflecting the presence of intracranial atherosclerotic lesions in the acute phase of cerebral infarction.

Predictive factors for progressive motor deficits in penetrating artery infarctions in two different arterial territories

BACKGROUND Progressive motor deficits (PMD) are common in cerebral penetrating artery disease (PAD) during the acute stage and leads to severe disability. Reliable predictors and stroke mechanism for PMD in PAD have been yet to be elucidated. Moreover, difference of predictors between topographically classified PAD has not ever been systematically studied. METHODS Three hundred ninety two consecutive patients with acute PAD (<20 mm) who showed lacunar motor syndrome and admitted within 24 h after onset were selected for this study. Patients were divided into 2 groups whose infarcts were topographically located within the territories of lenticulostriate arteries (LSA), and anterior pontine arteries (APA). Within each of the 2 groups, factors associated with PMD were analyzed. RESULTS Progressive motor deficits were found in 55 patients (21.0%) in LSA group and 38 patients (29.0%) in APA group. In multivariate analysis, female sex and severity of motor deficit on admission (NIHSS 5 or more) were common independent predictors for PMD in both groups. The specific predictors were single infarcts without concomitant silent lacunar infarcts and preceding TIAs in LSA group and diabetes mellitus in APA group. CONCLUSIONS Predictive factors for PMD were different in the 2 different territory groups. Diabetes mellitus was particularly associated with PMD in APA group.

The infarct location predicts progressive motor deficits in patients with acute lacunar infarction in the lenticulostriate artery territory

BACKGROUND AND PURPOSE Patients with acute lacunar infarction in the lenticulostriate artery (LSA) territory often show progression of motor deficits (PMD) after admission. The purpose of our study is to identify predictors for PMD using the findings of diffusion-weighted imaging (DWI) on admission. METHODS From January 2005 to December 2008, we studied 60 consecutive patients with acute lacunar infarction in the LSA territory within 24h after onset. To identify predictors for PMD, clinical characteristics including vascular risk factors and DWI findings were evaluated. DWI findings included the size and location of the infarcts and the slice numbers of infarcts visible on DWI. For the location, posterior type was defined as an infarct located in the posterior part of corona radiata on the second slice from the top among slices including corona radiata. RESULTS Twenty-six patients (43%) showed PMD. In univariate analysis, age >or=75 (P=0.03), female sex (P=0.04), infarct slice number >or=3 (P=0.04), and posterior type infarct (P<0.001) were more frequent in the PMD group than in the no PMD group. In multivariate analysis, posterior type infarct was the only independent predictor among DWI findings for PMD (odds ratio, 14.83; 95% confidence interval, 3.54-87.21, P<0.001). CONCLUSIONS Posterior type infarct was the independent predictor in DWI findings for PMD in patients with lacunar infarction in the LSA territory. We postulate that the posterior type infarct may affect the corticospinal tract to a greater degree and cause PMD.

Chronic kidney disease, 24-h blood pressure and small vessel diseases are independently associated with cognitive impairment in lacunar infarct patients

Although the relationships between chronic kidney disease (CKD) and cognitive impairment (CI) have been highlighted, the etiology of CI in CKD remains uncertain. Subjects comprised 224 consecutive patients with symptomatic lacunar infarction who underwent magnetic resonance imaging and ambulatory blood pressure monitoring (ABPM). Diurnal blood pressure (BP) patterns were categorized into three groups: dippers, non-dippers and risers. Lacunar infarcts (LIs), including both symptomatic and silent and diffuse white matter lesions (WMLs), were graded into three grades according to their degree. The results of kidney function were evaluated using estimated glomerular filtration rate (eGFR), categorized into three groups: stage 1, >60; stage 2, 30–60; and stage 3, <30 ml min–1 per 1.73 m2. There were 44 patients with CI. Confluent WMLs, including WML 2 and WML 3, were found in 36 patients (81.8%), and multiple lacunae including LI 2 and LI 3 were found in 30 patients (68.1%) with CI. Age >75 years (odds ratio (OR), 5.5; P<0.05), male sex (OR, 2.8; P<0.05), non-dippers (OR, 6.3; P<0.05) and risers (OR, 5.6; P<0.05), eGFR 30–60 ml min–1 per 1.73 m2 (OR, 2.9; P<0.05) and eGFR <30 ml min–1 per 1.73 m2 (OR, 23.8; P<0.01), WML grade 2 (OR, 5.1; P<0.01) and WML grade 3 (OR, 45.2; P<0.001) and LI grade 2 (OR, 3.2; P<0.05) and LI grade 3 (OR, 6.4; P<0.05) were independently associated with CI. Age >75 years (OR, 4.1; P<0.05), eGFR 30–60 ml min–1 per 1.73 m2 (OR, 3.7; P<0.05) and eGFR <30 ml min–1 per 1.73 m2 (OR, 8.7; P<0.05) were independently associated with WML grade 3. Extensive small vessel diseases, CKD and non-dipping status were independently associated with CI. CKD appears to mainly contribute to vascular CI, whereas possibilities of overlapping with other mechanisms such as degenerative CI cannot be excluded. Strict night time BP control and renoprotective treatment may be warranted to prevent CI.

Impact of Chronic Kidney Disease on Carotid Atherosclerosis According to Blood Pressure Category The Suita Study

Background and Purpose— We aimed to clarify the association of chronic kidney disease (CKD) with carotid atherosclerosis and the impact of CKD on carotid atherosclerosis according to blood pressure categories in an urban general population. Methods— We studied 3466 Japanese individuals (35–93 years old) in the Suita Study. Carotid atherosclerosis was expressed as the maximum carotid intima-media thickness and the presence of stenosis (>25%). The estimated glomerular filtration rate was calculated using the equations recommended by the Japanese Society of Nephrology. CKD was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. Blood pressure categories were defined by the European Society of Hypertension and European Society of Cardiology 2007 criteria. Results— The multivariable-adjusted maximum carotid intima-media thickness and odds ratio for stenosis in subjects with estimated glomerular filtration rate <50 mL/min per 1.73 m2 were greater than those in subjects with estimated glomerular filtration rate ≥90 mL/min per 1.73 m2. When subjects were stratified according to blood pressure categories, the multivariable-adjusted maximum carotid intima-media thickness was significantly greater in CKD subjects than in non-CKD subjects only in subjects with hypertension. Similarly, the impact of CKD on stenosis was evident only in subjects with hypertension (multivariable-adjusted odds ratios for stenosis [95% confidence interval] were 2.21 [1.53–3.19] in non-CKD/hypertension and 3.16 [2.05–4.88] in CKD/hypertension compared with non-CKD/optimal blood pressure). Conclusions— In a general population, the association of CKD with carotid atherosclerosis was modest, but CKD was independently associated with carotid atherosclerosis in subjects with hypertension.

An Adult Case of Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody-associated Multiphasic Acute Disseminated Encephalomyelitis at 33-year Intervals

Acute disseminated encephalomyelitis (ADEM) followed by optic neuritis (ON) has been reported as a distinct phenotype associated with anti-myelin oligodendrocyte protein (MOG) antibody. We herein report the case of a 37-year-old woman who was diagnosed with ADEM at 4 years old of age and who subsequently developed ON followed by recurrent ADEM 33 years after the initial onset. A serum analysis showed anti-MOG antibody positivity. This phenotype has only previously been reported in pediatric cases. Neurologists thus need to be aware that the phenotype may occur in adult patients, in whom it may be assumed to be atypical multiple sclerosis.

Preferred Involvement of the Basal Ganglia After Lenticulostriate Infarction as a Possible Indicator of Different Gray and White Matter Vulnerability

Background and Purpose— Symptomatic progression is frequently observed in lacunar infarcts. The exact mechanisms of this phenomenon have not yet been clarified. Summary of Cases— We report 2 patients with lenticulostriate artery infarcts that presented with skip lesions that were restricted to gray matter. One of the patients subsequently developed symptomatic deterioration; the other experienced no further neurological events. Conclusions— A possible mechanism of differential vulnerability to ischemia of gray and white matter is considered. White matter may have a longer therapeutic time window for neuroprotective treatment than gray matter.

Myasthenic symptoms in anti-low-density lipoprotein receptor-related protein 4 antibody-seropositive amyotrophic lateral sclerosis: Two case reports

BackgroundMyasthenic symptoms can be present in patients with amyotrophic lateral sclerosis (ALS). These symptoms have been considered to be caused by the degeneration of distal motor neurons and the neuromuscular junction (NMJ). Recent studies suggested that antibody to low-density lipoprotein receptor-related protein 4 (LRP4) was a pathogenic agent of myasthenia gravis (MG), and it was also detected in ALS patients.Case presentationPatient 1: A 58-year-old Japanese man developed progressive weakness and subsequent myasthenic symptoms including oculomotor disturbance. Clinical examination and electrophysiological studies confirmed upper and lower motor neuron involvement and NMJ dysfunction, and anti-LRP4 antibody was detected in his serum. A series of immunotherapies, including steroid pulse therapy, intravenous immunoglobulin, and plasmapheresis, was performed, and the myasthenic symptoms partially improved. The titer of anti-LRP4 antibody subsequently decreased. However, the therapeutic effect was transient, and ALS symptoms progressed. His clinical findings fulfilled the criteria of probable ALS using the Awaji criteria. Patient 2: A 74-year-old Japanese man suffered from progressive weakness of all limbs and dropped head in the evening. He complained of diplopia with a lateral horizontal gaze. Probable ALS was diagnosed because of the upper and lower motor neuron signs, whereas anti-LRP4 antibody was detected. Several immunotherapies were administered, and the myasthenic symptoms partially responded to each therapy. However, the truncal muscle weakness progressed, and he died of respiratory failure.ConclusionWe report two anti-LRP4 antibody-seropositive ALS patients with myasthenia who were not typical of ALS patients, and showed partial responses to immunotherapies. The anti-LRP4 antibody-seropositive status may influence developing ALS and cause additional ALS symptoms.

シンポジウム11―1 脳梗塞臨床の第一線における問題点：Branch atheromatous disease（BAD）をどう考え，どう対処するか Branch atheromatous disease（BAD）の概念とその臨床的意義

Small deep brain infarcts are often caused by two different vascular pathologies: 1. atheromatous occlusion at the orifice of large caliber penetrating arteries termed branch atheromatous disease (BAD) and 2. lipohyallinotic degenerative changes termed lipohyalinitic degeneration (LD). Atheromatous changes at the origin or proximal portion of a penetrating artery of larger caliber can be observed in infarcts of the lenticulostriate (LSA) as well as the anterior pontine arteries (APA). We studied 392 patients with penetrating artery disease in the territories of LAS and APA to evaluate predictive factors for progressive motor deficits (PMD). Prevalence of male gender, diabetes mellitus and intracranial atherosclerosis were significantly higher in the APA group than in the LSA group. Female sex and initial severity of motor deficit were common predictors for PMD in both groups. In the LSA group, single infarcts without concomitant silent lacunar infarcts and lacunar TIAs were found to be independent predictors for PMD. In the APA group, diabetes mellitus was found to be an independent predictor. Combined treatment consisting of argatroban, cilostazol, and edaravone for acute BAD type infarct significantly improved the functional outcome.