Incidence, predictors, and etiology of subsequent ischemic stroke within one year after transient ischemic attack.

Background Incidence and predictors of ischemic stroke in patients with transient ischemic attack (TIA) have not been fully clarified outside Europe and North America. Aims We undertook the present prospective, multicenter study to clarify the incidence, predictors, and etiology of ischemic stroke within one year of TIA onset in Japan. Methods The study subjects were patients within seven days of TIA onset who were enrolled in a prospective register from 57 hospitals between June 2011 and December 2013. The primary endpoint was occurrence of ischemic stroke. Results Of 1365 consecutive patients, 1245 were followed for one year after TIA onset; 101 (8.1%) experienced ischemic stroke during follow-up. The leading subtype of ischemic stroke was small-vessel occlusion (SVO) followed by large-artery atherosclerosis (LAA) attributable to intracranial artery diseases. When dividing ischemic stroke events between those occurring within the first 90 days after TIA onset and those occurring after the first 90 days, the leading subtype of ischemic stroke within the first 90 days after TIA onset was SVO, followed by LAA attributable to intracranial artery diseases. In comparison, the subtypes most commonly seen beyond the first 90 days after TIA onset were cardioembolic and LAA attributable to intracranial artery disease. The one-year risk of ischemic stroke increased significantly as ABCD2 score increased, at 6.2% for 0-3 points, 7.2% for 4-5 points, and 11.6% for 6-7 points. Conclusions The one-year ischemic stroke risk after TIA was about 8% and was associated with the ABCD2 score. The most common subtype of subsequent ischemic stroke was SVO.

Differences in Clinical Characteristics between Patients with Transient Ischemic Attack Whose Symptoms Do and Do Not Persist on Arrival.

BACKGROUND: Symptoms of transient ischemic attack (TIA) persist on arrival and subsequently resolve in some patients admitted to hospitals early after onset. Differences in clinical characteristics between patients with acute TIA whose symptoms do and do not persist on arrival remain unclear. METHODS: We retrospectively extracted data of consecutive TIA patients with an onset-to-door time (ODT) of 24 hours or less and without a history of stroke from a multicenter TIA database. Clinical characteristics were compared between patients with and without persisting symptoms on arrival. RESULTS: Two hundred sixty-six patients (158 men, 68.0 ± 12.9 years) were included. Of the total number of patients, 105 (39.5%) had persisting symptoms with a mean National Institutes of Health Stroke Scale score of 2.4 (median, 1.0). Patients with persisting symptoms were more likely to have sensory disorder, ambulance-transported admission, long-duration TIA (≥60 minutes), and shorter ODT than those without. Multivariate analysis showed that sensory disorder (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.35-4.77), ambulance-transported admission (OR 1.80, 95% CI 1.00-3.28), and long-duration TIA (OR 3.96, 95% CI 2.12-7.71) were positively associated and that an ODT of more than 12 hours (OR .18, 95% CI .04-.63) was inversely associated with the presence ofpersisting symptoms. Patients with persisting symptoms were more likely to be examined by a stroke physician at first (69% versus 57%, P = .049) and then hospitalized in a stroke unit (59% versus 43%, P = .010). CONCLUSION: Clinical manifestations and management after admission might differ between patients with acute TIA whose symptoms do and do not persist on arrival.

Cognitive impairment of Japanese multiple sclerosis patients: Follow-up study using BRB-N assessment tool.

OBJECTIVES: The purpose of this study was to evaluate cognitive function in patients with multiple sclerosis (MS), compared with control subjects, and to establish whether decline of cognitive function continues in the patients during remission. METHODS: The Japanese version of the Brief Repeatable Battery of Neuropsychological tests (BRB-N), which includes the selective reminding test (SRT), spatial recall test (SPART), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), and the word list generation test (WLG), was performed in 34 Japanese patients with MS (8 males, 26 females; mean age, 42 years) and in 37 age- and education-matched healthy controls (20 males, 17 females; mean age, 36 years). BRB-N was conducted at intervals of two years for MS patients who remained in remission, and the cognitive changes were evaluated by comparing the results with those of the initial examination at entry into the study. RESULTS: The MS patients showed lower BRB-N scores than controls, with high significance in the SRT, SRT-D, SDMT and PASAT tests (p<0.01). The BRB-N scores of the MS patients who remained in remission were not significantly changed for at least 2 years. CONCLUSIONS: The Japanese version of the BRB-N is useful to clarify the nature of cognitive impairment in Japanese MS patients. Based on this neuropsychological assessment, we suggest that working memory and information-processing speed are key deficits. Patients who remained in remission showed little or no further impairment of cognitive functions for at least two years.

Clinical Characteristics of Transient Ischemic Attack Patients with Atrial Fibrillation: Analyses of a Multicenter Retrospective Study.

BACKGROUND: Atrial fibrillation (AF) is an important risk factor for transient ischemic attack (TIA). However, little is known about the characteristics of TIA patients with AF. This study investigated the characteristics of such patients, using data from a retrospective, observational, multicenter study. METHODS: TIA patients admitted to 13 stroke centers in Japan within 7 days of onset between January 2008 and December 2009 were included. The present analyses compared baseline characteristics, clinical symptoms, findings from diffusion-weighted imaging (DWI), and clinical outcomes between patients with and without AF (AF and non-AF groups). RESULTS: A total of 464 patients (292 men; mean age 68.5 ± 13.2 years) were registered. Of these, 79 patients (17%) had AF. Patients in the AF group were older (73.9 ± 9.1 vs. 67.4 ± 13.6 years, p < 0.001) and more likely to show disturbance of consciousness (13 vs. 6%, p = 0.046) and aphasia (9 vs. 3%, p = 0.007) than patients in the non-AF group. Although no difference in the overall DWI-positive rate was seen between the groups (28 vs. 20%, p = 0.102), a single lesion (23 vs. 10%, p < 0.001), a lesion ≥15 mm (11 vs. 4%, p = 0.006), and a single lesion ≥15 mm (11 vs. 2%, p < 0.001) on DWI were more frequent in the AF group. Multivariate logistic regression analysis identified increased age [odds ratio (OR) 1.04; 95% confidence interval (CI) 1.02-1.07] and DWI single lesion ≥15 mm (OR 5.67; 95% CI 1.92-16.7) as independently associated with the presence of AF. CONCLUSIONS: In this study, 17% of our TIA patients had AF. We found an association between the acute ischemic lesion pattern on DWI of a single lesion ≥15 mm and AF in TIA patients. These results might lead to a better diagnosis of TIA patients with AF.

Incidence and predictors of ischemic stroke events during hospitalization in patients with transient ischemic attack.

BACKGROUND: The purpose of this study was to elucidate the incidence and predictors of ischemic stroke or recurrent transient ischemic attack (TIA) during acute hospitalization in patients with TIA. METHODS: We carried out a multicenter retrospective study to clarify the characteristics of in-patients with TIA. The subjects of this study were TIA patients admitted to 13 stroke hospitals within 7 days after onset between 2008 and 2009. TIA was defined as focal neurologic symptoms ascribable to a vascular etiology lasting less than 24 h. We investigated the incidence and predictors of ischemic events including ischemic stroke or recurrent TIA during hospitalization. RESULTS: A total of 464 patients with TIA (292 men, 69 ± 13 years) were registered. Of those, 400 (86.2%) were admitted within 24 h of TIA onset. The mean length of hospital stay was 13 days. During hospitalization, 8 patients had ischemic strokes and 26 had recurrent TIAs. The leading subtype of 8 ischemic strokes was small vessel disease (n = 3) followed by cardioembolism (n = 2). Multiple logistic regression analysis showed that hypertension (OR: 3.41; 95% CI: 1.23-12.3), MRI-diffusion-weighted image positivity (OR: 2.49; 95% CI: 1.15-5.25), and hemiparesis (OR: 2.30; 95% CI: 1.02-5.88) were independently associated with ischemic events during hospitalization. CONCLUSIONS: In this study, 1.7% of patients with TIA had ischemic stroke during acute hospitalization, and the most common subtype was small vessel disease. Subsequent ischemic stroke and recurrent TIA were associated with hypertension, positive DWI findings, and hemiparesis.

Features of patients with transient monocular blindness: a multicenter retrospective study in Japan.

BACKGROUND: Transient monocular blindness (TMB) is associated with a transient ischemic attack (TIA). The purpose of this study was to investigate the features of TMB in the Japanese population using data from a multicenter retrospective study of TIA. METHODS: The subjects were consecutive TIA patients admitted to 13 stroke centers within 7 days after symptom onset. We compared clinical characteristics of patients with TMB and those without TMB who had other symptoms of cerebral TIA. RESULTS: A total of 464 patients were registered between January 2008 and December 2009, and 444 patients (283 men, mean age: 68.5 years) were included in the analysis. Thirteen patients (2.9%) presented with TMB. Patients with TMB were less likely to arrive at the specialized stroke center quickly than those without TMB (P = .013). Stenotic lesions in the extracranial internal carotid artery were more common in patients with TMB (33.3% versus 9.1%, P = .022). CONCLUSIONS: TMB was not common in our TIA inpatients. This study suggests that patients with TMB should immediately undergo a diagnostic workup, including brain and vessel imaging, and cardiac evaluation, as is performed in patients with other cerebral TIA symptoms. A larger, prospective cohort is needed to confirm the risks and outcomes of patients with TMB in the Japanese population.

Factors associated with onset-to-door time in patients with transient ischemic attack admitted to stroke centers.

BACKGROUND AND PURPOSE: The aim of this study was to elucidate the factors associated with the time from symptom onset to arrival at a stroke center (onset-to-door time [ODT]) in patients with classically defined transient ischemic attack using data from a multicenter, retrospective study. METHODS: The subjects were patients with transient ischemic attack admitted to 13 stroke centers in Japan within 7 days of onset between 2008 and 2009. A total of 464 patients registered (292 men, 68.5±13.2 years old), and 421 of them (268 men, 68.8±13.1 years old) were included in the analyses. ODT was classified into the following 5 categories: <3 hours, 3 to 6 hours, 7 to 12 hours, 13 to 24 hours, and >24 hours. RESULTS: There were 233 patients (55.3%) who visited a stroke center within 3 hours of symptom onset. Multiple ordinal logistic regression analysis revealed that motor weakness, speech disturbance, and duration of symptoms >10 minutes were independently associated with a short ODT. Furthermore, a history of transient ischemic attack and hypertension and a referral from another medical facility were independently associated with a long ODT. Patients with a higher ABCD2 score were likely to arrive at a stroke center more quickly. CONCLUSIONS: We identified several factors that were positively and negatively associated with the ODT in patients with transient ischemic attack.

A Patient with Hashimoto's Encephalopathy Presenting with Convulsive Seizure Alone as the Initial Symptom.

A 71-year-old Japanese woman with Sjögren syndrome, Hashimoto's disease and a 6-month history of cognitive impairment was admitted to our hospital because of consciousness disturbance and convulsion. Her convulsive seizure disappeared by intravenous administration of diazepam following carbamazepine, and conscious level became alert the next day. But, her cognitive function was persistently deteriorated, and a score of mini-mental state examination (MMSE) was 17/30 points. Magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) of the brain did not show any abnormal findings. The electroencephalogram showed increased slow waves in bilateral parieto-occipital regions. Serum anti-thyroglobulin antibodies were elevated (1780 U/ml), but thyroid function was within the normal range. In addition, anti-NAE (NH2-terminal of α-enolase) antibodies were positive. We diagnosed Hashimoto's encephalopathy, and started steroid therapy. Her cognitive function gradually improved after steroid therapy, and convulsive seizure did not recur until 3 months later. We emphasize that Hashimoto's encephalopathy should be considered even in patients with convulsive seizure of adult onset without thyroid dysfunction.

Effect of single nucleotide polymorphisms of the prostacyclin receptor gene on platelet activation in Japanese healthy subjects and patients with cerebral infarction.

Cerebral infarction (CI) is a complex multifactorial disorder that is thought to result from the interaction of various environmental factors and an individual's genetic make-up, including genes associated with platelet activation. In order to clarify whether single nucleotide polymorphisms (SNPs) of the prostacyclin receptor (IP) gene affects platelet activation in ischemic stroke, we investigated the relationship between platelet function and genetic polymorphism of the coding sequence of the IP gene in 64 Japanese patients with CI and 54 healthy subjects. We determined the entire nucleotide sequence of the IP gene in healthy Japanese subjects, and found that an adenine (A) to cytosine (C) substitution at base 984 (A984C) in exon 3 is the most frequent SNP. Using flow cytometry, the power-transformed mean percentage of PAC-1-positive platelets, [PAC-1](1/3), was significantly higher in healthy subjects with the C/C genotype than in healthy subjects with the A/A genotype (p ≤ 0.05), although there was no significant difference in patients with CI between these two genotypes. Furthermore, we genotyped 158 control patients and 106 patients with CI. The homozygous C/C genotype was more frequently found in the CI group (46.2%) than in the healthy control group (17.1%; p < 0.001). The present report is the first to show an association between the A984C polymorphism of the IP gene and platelet activation in Japanese subjects. This polymorphism may be clinically significant in disorders in which prostacyclin plays a key role, such as CI.

Bleeding Brunner's Gland Hyperplasia of the Duodenum: A Case Report With a Review of the Japanese Literature.

A man taking antithrombotic agents was admitted because of melena. Upper gastrointestinal endoscopy revealed a large, pedunculated polyp bleeding from erosions on its top. The polyp was endoscopically resected, and histopathologically diagnosed as Brunner's gland hyperplasia. It is commonly encountered as a small, raised lesion, but may enlarge or bleed. We report this case, with a review of the Japanese literature and discussion of the mechanism of bleeding.

Examination timing and lesion patterns in diffusion-weighted magnetic resonance imaging of patients with classically defined transient ischemic attack.

BACKGROUND: This study investigated factors associated with the presence of acute ischemic lesions after transient ischemic attack (TIA), using diffusion-weighted imaging (DWI) data from a multicenter retrospective, observational study. METHODS: Of the 464 patients admitted to 13 stroke centers in Japan within 7 days after TIA onset, 458 patients underwent a DWI examination in this registry. Patients were divided into those with acute ischemic lesions and those without. We analyzed associations between DWI lesions and baseline characteristics, including age, sex, comorbidities, large artery atherosclerosis (LAA), type and duration of symptoms, the presence of multiple occurrences of TIA within 90 days before hospital visits (multiple TIAs) and the time from symptom onset to DWI examination (time-to-DWI). RESULTS: Among the 458 patients (291 men, 68.4±13.2 years old), 374 (81.7%) underwent a DWI examination within the initial 24 hours after the symptom onset. DWI lesions were found in 96 patients (21.0%), and divided into a single lesion (56 patients, 12.2%) or multiple lesions (40 patients, 8.7%). The presence of DWI lesions had an association with male sex (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.07-3.29), time-to-DWI longer than 24 hours (OR 2.96; CI 1.57-5.52), and intracranial LAA (OR 1.99; CI 1.02-3.79). The presence of a single DWI lesion had an association with atrial fibrillation (OR 2.70; CI 1.41-5.03), and multiple DWI lesions did with time-to-DWI longer than 24 hours (OR 6.20; CI 2.60-15.20), multiple TIAs (OR 3.04; CI 1.35-6.76), intracranial LAA (OR 3.63; CI 1.44-8.89), and extracranial LAA (OR 3.53; CI 1.08-10.78). CONCLUSIONS: Acute ischemic lesions on DWI were associated with time-to-DWI and LAA in patients with classically defined TIA. Additionally, we identified some differences in relating factors between patients with single and multiple DWI lesions. These results indicate that time-to-DWI and DWI lesion pattern may be important for the diagnosis and management of TIA.

Phase I study of intravenous low-dose granulocyte colony-stimulating factor in acute and subacute ischemic stroke.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF; filgrastim) may be useful for the treatment of acute ischemic stroke because of its neuroprotective and neurogenesis-promoting properties, but an excessive increase of neutrophils may lead to brain injury. We examined the safety and tolerability of low-dose G-CSF and investigated the effectiveness of G-CSF given intravenously in the acute phase (at 24 hours) or subacute phase (at 7 days) of ischemic stroke. METHODS: Three intravenous dose regimens (150, 300, or 450 µg/body/day, divided into 2 doses for 5 days) of G-CSF were examined in 18 patients with magnetic resonance imaging (MRI)-confirmed infarct in the territory of the middle cerebral artery. Nine patients received the first dose at 24 hours poststroke (acute group) and 9 patients received the first dose on day 7 poststroke (subacute group; n = 3 at each dose in each group). A scheduled administration of G-CSF was skipped if the patient's leukocyte count exceeded 40,000/µL. Patients received neurologic and MRI examinations. RESULTS: We found neither serious adverse event, drug-related platelet reduction nor splenomegaly. Leukocyte levels remained below 40,000/µL at 150 and 300 µg G-CSF/body/day, but rose above 40,000/µL at 450 µg G-CSF/body/day. Neurologic function improvement between baseline and day 90 was more marked after treatment in the acute phase versus the subacute phase (Barthel index 49.4 ± 28.1 v 15.0 ± 22.0; P < .01). CONCLUSIONS: Low-dose G-CSF (150 and 300 µg/body/day) was safe and well tolerated in ischemic stroke patients, and leukocyte levels remained below 40,000/µL.

Seasonal variation of stroke incidence in Japan for 35631 stroke patients in the Japanese Standard Stroke Registry, 1998-2007.

BACKGROUND: Seasonal variation of stroke incidence has been reported in many countries. The present study was designed to elucidate seasonal and monthly variations in the incidence of subtypes of acute ischemic stroke and hypertensive hemorrhagic stroke using the Japanese Standard Stroke Registry Study (JSSRS) database, which is currently the world's largest hospital-based stroke database, accumulating records from 163 Japanese institutions. METHODS: Among 47,782 patients with acute stroke registered with JSSRS between 1998 and 2007, we selected 35,631 for analysis (patients with ischemic or hemorrhagic stroke of unknown etiology were excluded). A simple moving average was used to examine monthly variation of stroke incidence. We also examined seasonal variation of ischemic stroke subtypes. RESULTS AND CONCLUSIONS: Monthly variation in incidence of all ischemic stroke was significant (P < .001). Noncardioembolic ischemic stroke was more frequent in summer than in winter (P < .001). Lacunar stroke showed higher incidence in summer than in winter (P < .001), although the increase did not reach significance for atherothrombotic stroke (P = .057). In contrast, cardioembolic stroke (P < .001) and hemorrhagic stroke (P < .001) occurred more frequently in winter than in summer. Hemorrhagic stroke showed a regional difference of incidence between northern and southern Japan. There is a temporal variation of stroke incidence in Japan, with different patterns of variation depending on stroke subtype. These findings may help in developing strategies for preventing stroke.

Appearance of WBC-platelet complex in acute ischemic stroke, predominantly in atherothrombotic infarction.

AIM: Platelet aggregates with white blood cells (WBC-platelet complex) have recently been proposed as a marker of activated platelets, in addition to well-known molecular markers. We aimed to investigate the colocalization of activated platelets and WBC-platelet complex by means of flow cytometry, in patients with ischemic stroke. METHODS: Eighty-six patients with cerebral infarction (CI) in the acute phase (58 males, 28 females; 65±14 years old) and 62 non-CI controls (23 males, 39 females; 53±14 years old) were registered. The appearance of WBC-platelet complex was quantified using 3-color flow cytometry. RESULTS: The appearance rate of WBC-platelet complex was significantly higher in the CI group than in the controls. The appearance rate of WBC-platelet complex was significantly higher in atherothrombotic infarction (AT) than in lacunar infarction (LA) (p < 0.05). Furthermore, positive rates of both monocyte-platelet complex and granulocyte-platelet complex, but not lymphocyte-platelet complex, were significantly higher in the AT group than in the controls. CONCLUSION: We concluded that WBC-platelet complex, especially involving monocytes and granulocytes, is a novel marker of platelet activation in the acute phase of ischemic stroke, mainly in AT.

Hemiplegic peripheral neuropathy accompanied with multiple cranial nerve palsy.

A 32-year-old man experienced double vision around January, 2010, followed by weakness of his left upper and lower extremities. Articulation disorders and loss of hearing in his left ear developed, and he was admitted to our hospital on February 14, 2010. Physical examination was normal, and neurological examination showed clear consciousness with no impairment of cognitive function, but with articulation disorders. Olfactory sensation was reduced. Left ptosis and left gaze palsy, complete left facial palsy, perceptive deafness of the left ear, and muscle weakness of the left trapezius muscle were observed. Paresis in the left upper and lower extremities was graded 4/5 through manual muscle testing. Sensory system evaluation revealed complete left-side palsy, including the face. Deep tendon reflexes were slightly diminished equally on both sides; no pathologic reflex was seen. No abnormality of the brain parenchyma, cerebral nerves or cervicothoracolumbar region was found on brain magnetic resonance imaging. On electroencephalogram, alpha waves in the main frequency band of 8 to 9 Hz were recorded, indicating normal findings. Brain single photon emission computed tomography (SPECT) scan showed reduced blood flow in the right inner frontal lobe and both occipital lobes. Nerve biopsy (left sural nerve) showed reduction of nerve density by 30%, with demyelination. The patient also showed manifestations of multiple cranial nerve disorder, i.e., of the trigeminal nerve, glossopharyngeal nerve, vagus nerve, and hypoglos-sal nerve. Whole-body examination was negative. Finally, based on ischemic brain SPECT images, spinal fluid findings and nerve biopsy results, peripheral neuropathy accompanied with multiple cranial nerve palsy was diagnosed.

Relationship between chronic kidney disease and white matter hyperintensities on magnetic resonance imaging.

Renal dysfunction may be related to cerebral small-vessel disease. This study aimed to assess the relationship between mild renal dysfunction and various white matter hyperintensities on magnetic resonance imaging (MRI). A total of 2106 subjects (1368 men and 738 women; mean age, 56 ± 10 years) without a history of stroke were enrolled in the study. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR), calculated using the relationship 194Cr(-1.094) × age(-0.287) × 0.739 (if female), where Cr is serum creatinine concentration. White matter hyperintensity on T2-weighted MRI was classified as deep and/or subcortical white matter hyperintensity (DSWMH), periventricular hyperintensity (PVH), or asymptomatic cerebral infarction (ACI). The prevalence of ACI, DSWMH, and PVH was significantly correlated with degree of eGFR reduction; in the subgroups with eGFR ≥ 90, 60∼89, and <60 mL/min/1.73 m(2), the following prevalences were found: ACI, 7%, 6%, and 16%; DSWMH, 18%, 21%, and 37%; PVH: 7%, 10%, and 21%. The odds ratios for ACI, DSWMH, and PVH of eGFR <60 mL/min/1.73 m(2) were significantly increased, to 2.11 (95% confidence interval [CI], 1.23-3.61; P = .006), 2.26 (1.53-3.34; P < .001), and 2.81 (1.67-4.72; P < .001), respectively. Our data indicate that mild renal dysfunction may be associated with an increase in cerebral small-vessel disease independent of hypertension.

Chronic kidney disease in patients with ischemic stroke.

To examine the significance of renal dysfunction in patients who have sustained ischemic stroke, we examined the relationship between the renal function evaluated in terms of estimated glomerular filtration rate (eGFR) and the subtype of brain infarction (BI) in patients with ischemic stroke. A total of 639 patients with BI were enrolled in this study, with 314 subjects without stroke or transient ischemic attack registered as age-matched controls. eGFR was calculated according to the equation 194 × Cr(-1.094) × Age(-0.287) (-0.739 if female), where Cr is serum creatinine concentration, and was classified into four stages: stage I, eGFR ≥ 90 mL/min/1.73 m(2); stage II, eGFR 60 ~ 89 mL/min/1.73 m(2); stage III, eGFR 30 ~ 59 mL/min/1.73 m(2); and stage IV, eGFR <29 mL/min/1.73 m(2). Stage III-IV was significantly more prevalent in the BI group (38%) than in the control group (22%; P < .001). The odds ratio for stage III-IV was significantly higher in the BI group (1.93; 95% confidence interval [CI], 1.35-2.76). Among the BI subgroups, the odds ratios of stage III-IV for the atherothrombotic type (1.81; 95% CI, 1.23-2.68) and the cardiogenic type (2.25; 95% CI, 1.32-3.83) were significantly higher than that of the control group, but that of stage III-IV for lacunar type was not (1.67; 95% CI, 0.98-2.84). Our results indicate that ischemic stroke is frequently associated with renal dysfunction. Chronic kidney disease might be independent risk factor for infarction, especially for cardiogenic and atherosclerotic types.

Is mild renal dysfunction a risk factor for carotid atherosclerosis in apparently healthy adults?

OBJECTIVE: Renal dysfunction may be related to cerebrovascular disease. The aim of this study was to assess the relationship between mild renal dysfunction and carotid artery atherosclerosis detected by ultrasonography in apparently healthy subjects. METHODS: A total of 2,106 persons (1,368 men and 738 women, mean age+/-S.D.: 56 +/- 10 years) with no history of stroke were enrolled. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR), calculated by using the relationship 194Cr(-1.094)×Age(-0.287)×0.739 (if female), where Cr is serum creatinine concentration. Atherosclerosis on ultrasonography was defined as regional intimal thickening or nodular lesion. RESULTS: Atherosclerotic lesions were significantly more frequent in subjects with CKD stage 3 than in CKD stage 1 or 2 (p<0.001). Odds ratios for atherosclerotic lesions were significantly increased to 1.11 (95% confidence interval: 1.09-1.12, p<0.001) for increasing age, 1.66 (1.31-2.10, p<0.001) for male sex, 1.76 (1.43-2.16, p<0.001) for systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg, 1.61 (1.28-2.01, p<0.001) for LDL-cholesterol ≥140 mg/dL, and 1.59 (1.23-2.05, p=0.003) for smoking habit versus no risk factor. The odds ratio of CKD stage 3 for ≥50% carotid artery stenosis was significantly increased to 3.47 (1.09-11.08, p=0.035), although CKD stage 2 and stage 3 were not significant (0.77, 95% CI: 0.59-1.01, p=0.068; 0.99, 95%CI: 0.67-1.46, p=0.981, respectively). CONCLUSION: Renal dysfunction defined in terms of eGFR might be associated with early-stage carotid atherosclerosis, but traditional vascular risk factors, including increasing age or hypertension, appear to play a major role.

Inositol hexakisphosphate kinases induce cell death in Huntington disease.

Inositol pyrophosphate diphosphoinositol pentakisphosphate is ubiquitously present in mammalian cells and contains highly energetic pyrophosphate bonds. We have previously reported that inositol hexakisphosphate kinase type 2 (InsP(6)K2), which converts inositol hexakisphosphate to inositol pyrophosphate diphosphoinositol pentakisphosphate, mediates apoptotic cell death via its translocation from the nucleus to the cytoplasm. Here, we report that InsP(6)K2 is localized mainly in the cytoplasm of lymphoblast cells from patients with Huntington disease (HD), whereas this enzyme is localized in the nucleus in control lymphoblast cells. The large number of autophagosomes detected in HD lymphoblast cells is consistent with the down-regulation of Akt in response to InsP(6)K2 activation. Consistent with these observations, the overexpression of InsP(6)Ks leads to the depletion of Akt phosphorylation and the induction of cell death. These results suggest that InsP(6)K2 activation is associated with the pathogenesis of HD.

Platelet aggregates detected by a conventional hematology analyzer method is a risk factor for stroke or a predictive factor in patients with chronic-stage cerebral infarction.

Assessment of platelet activation and/or function is important for primary and secondary prevention of vascular events. To test the hypothesis that determination of platelet aggregation in patients with chronic-stage cerebral infarction (CI) provides a simple measure of risk for ischemic stroke, we used a conventional hematology analyzer to detect aggregates and to assess the efficacy of antiplatelet agents in preventing spontaneous aggregate formation. Platelet aggregates were measured in citrated blood from 142 magnetic resonance imaging confirmed CI patients and 97 controls without CI (nonstroke). Aggregates were detected in 1 of 36 (2.8%) nonstroke subjects without risk factors, but in 24 of 52 (46.2%) nonstroke subjects with risk factors (odds ratio [OR], 3.32; 95% confidence interval [CI], 1.10-10.00), in 21 of 35 (60.0%) nonstroke subjects with a predictive factor (carotid artery intima-media thickness [IMT] >1.1 mm) (OR, 9.13; 95% CI, 2.70-30.48), and in 31 of 63 (49.2%) CI patients who had not received antiplatelet therapy (OR, 2.16; 95% CI, 1.12-4.17). After adjusting for other risk factors, the appearance of platelet aggregates was correlated only with IMT ≥1.1 mm. The rate of appearance of platelet aggregates was 0.33-fold lower in patients on antiplatelet therapy compared with those not on antiplatelet therapy (24.1%; 19 of 79 CI patients). Patients with platelet aggregates in the blood are considered at high risk for ischemic stroke, because the appearance of aggregates is associated with increased IMT. Our method is suitable for screening platelet function in high-risk patients and for examining the efficacy of antiplatelet agents.