Hiromitsu Naka

Association between cerebral microbleeds on T2*-weighted MR images and recurrent hemorrhagic stroke in patients treated with warfarin following ischemic stroke.

BACKGROUND AND PURPOSE: Although accumulating evidence suggests the presence of microbleeds as a risk factor for intracerebral hemorrhage (ICH), little is known about its significance in anticoagulated patients. The aim of this study was to determine whether the presence of microbleeds is associated with recurrent hemorrhagic stroke in patients who had received warfarin following atrial fibrillation–associated cardioembolic infarction. MATERIALS AND METHODS: A total of 87 consecutive patients with acute recurrent stroke, including 15 patients with ICH and 72 patients with cerebral infarction, were enrolled in this study. International normalized ratios (INRs), vascular risk factors, and imaging characteristics, including microbleeds on T2*-weighted MR images and white matter hyperintensity (WMH) on T2-weighted MR images, were compared in the 2 groups. RESULTS: Microbleeds were noted more frequently in patients with ICH than in patients with cerebral infarction (86.7% versus 38.9%, P = .0007). The number of microbleeds was larger in patients with ICH than in patients with cerebral infarction (mean, 8.4 versus 2.1; P = .0001). INR was higher in patients with ICH than in patients with cerebral infarction (mean, 2.2 versus 1.4; P < .0001). The frequency of hypertension was higher in patients with ICH than in patients with cerebral infarction (86.7% versus 45.8%, P = .0039). Multivariate analysis revealed that the presence of cerebral microbleeds (odds ratio, 7.383; 95% confidence interval, 1.052–51.830) was associated with ICH independent of increased INR and hypertension. CONCLUSION: The presence of cerebral microbleeds may be an independent risk factor for warfarin-related ICH, but more study is needed because of strong confounding associations with elevated INR and hypertension.

Magnetization transfer measurements of cerebral white matter in patients with myotonic dystrophy

To determine whether patients with myotonic dystrophy (MyD) have structural changes in the cerebral white matter, we performed magnetization transfer (MT) imaging of the cerebral white matter in 14 MyD patients and 11 age-matched normal controls. We calculated MT ratios in both the white matter lesions (WMLs) and the normal-appearing white matter (NAWM) of MyD patients using region of interest (ROI) analysis. MT ratios in WMLs were markedly decreased, and all ROIs in NAWM also showed significantly lower MT ratios in MyD patients than in normal controls. The average MT ratio of all ROIs in WMLs and NAWM in each patient showed a significant negative correlation with duration of illness, but not with the patients age or age at onset. The results of the present study indicate not only the presence of pathological changes in WMLs but also the widespread involvement of NAWM in MyD patients. The results also suggest that structural changes in the white matter may be progressive during the clinical course of MyD.

Magnetization Transfer Measurements of Brain Structures in Patients with Multiple System Atrophy

To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.

Antiplatelet Therapy as a Risk Factor for Microbleeds in Intracerebral Hemorrhage Patients: Analysis Using Specific Antiplatelet Agents

BACKGROUND Although brain microbleed has been reported to be a risk factor for antiplatelet-associated intracerebral hemorrhage, data on the use of specific antiplatelet agents are lacking. In this study, we examined the associations between specific antiplatelets and brain microbleeds in order to help select antiplatelet agents in patients with microbleeds. METHODS We evaluated 1914 consecutive acute stroke patients, including 412 patients with intracerebral hemorrhage and 1502 patients with ischemic stroke. The associations between the presence of microbleeds and antiplatelet use were evaluated, including specific antiplatelet agents (aspirin, clopidogrel, cilostazol, and ticlopidine). RESULTS Antiplatelet use was associated with the presence of microbleeds in patients with intracerebral hemorrhage (odds ratio [OR] 2.418; 95% confidence interval [CI] 1.236-4.730; P = .0099), but not in patients with ischemic stroke. The use of a single antiplatelet medication was not associated with the presence of microbleeds. In patients with intracerebral hemorrhage, aspirin (OR 2.160; 95% CI 1.050-4.443; P = .0364) but not clopidogrel, cilostazol, or ticlopidine was associated with microbleeds. In these patients, dividing brain microbleeds into deep microbleeds and lobar microbleeds revealed an association only between antiplatelet use and the presence of deep microbleeds (OR 2.397; 95% CI 1.258-4.567; P = .0079). None of the antiplatelet agents were associated with the presence of deep microbleeds, although aspirin had a trend of association (OR 1.986; 95% CI 1.000-3.946; P = .0501). CONCLUSIONS Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results.

Positional relationship between recurrent intracerebral hemorrhage/lacunar infarction and previously detected microbleeds.

BACKGROUND AND PURPOSE: Although MBs, ICH, and LI are secondary to cerebral microangiopathy, it remains unclear whether the location of subsequent ICH/LI corresponds to the previous location of MBs. We performed this study to clarify the positional relationship between recurrent ICH/LI and previously detected MBs. MATERIALS AND METHODS: We evaluated patients with recurrent ICH/LI who had MBs, as shown on prior T2*-weighted MR imaging. We assessed retrospectively whether the location of recurrent ICH/LI corresponded to that of the prior MB. Patients with ICH were divided into the deep ICH group and the lobar ICH group, and the positional relationship between hematoma and previously detected MBs was evaluated. RESULTS: A total of 55 patients, including 34 with recurrent ICH and 21 with recurrent LI were evaluated. Although the location of the LI corresponded to prior MBs in only 1 patient (4.8%), the location of ICH corresponded to prior locations of MBs in 21 patients (61.8%) (OR, 32.3; 95% CI, 3.86–270.3; P < .001). Among the patients with ICH, the correspondence ratio was higher in the deep ICH group (19 of 24 patients, 79.2%) than in the lobar ICH group (2 of 10 patients, 20%) (OR, 15.2; 95% CI, 2.42–95.3; P < .002). CONCLUSIONS: The close positional association between recurrent ICH and prior MBs suggests that MBs represent hemorrhage-prone microangiopathy. In addition, different correspondence ratios between the deep ICH group and the lobar ICH group may be attributable to their different pathogenesis.

Plasma total homocysteine levels are associated with advanced leukoaraiosis but not with asymptomatic microbleeds on T2*-weighted MRI in patients with stroke.

Both leukoaraiosis and asymptomatic microbleeds are associated with small‐artery diseases. Although an association between hyperhomocysteinemia and leukoaraiosis has been reported, no studies have evaluated the association between total homocysteine (tHcy) level and presence of microbleeds in stroke patients. We evaluated the association between tHcy level and leukoaraiosis or microbleeds in stroke patients. In 102 patients with stroke (69.5 ± 10.3 years old, 54 men and 48 women), microbleeds on T2*‐weighted MR images were counted, leukoaraiosis on T2‐weighted images was graded and fasting plasma tHcy concentrations were measured. Plasma tHcy level was significantly higher in patients with advanced leukoaraiosis than in those without advanced leukoaraiosis (13.9 ± 4.6 μmol/l vs. 10.2 ± 3.4 μmol/l, P < 0.0001). Plasma tHcy level was not significantly different in patients with microbleeds and those without microbleeds (11.3 ± 4.1 μmol/l vs. 11.4 ± 4.3 μmol/l, P = 0.9441). Elevated tHcy level is significantly and independently associated with advanced leukoaraiosis [odds ratio (OR), 1.330; 95% CI, 1.130–1.565] but not with the presence of microbleeds. Elevated tHcy level appears to be associated with ischemic small‐artery disease rather than with bleeding‐prone small‐artery disease.

The Association between Hyperintense Vessel Sign and Final Ischemic Lesion Differ in Its Location

BACKGROUND The hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery images can frequently be detected in patients with acute cerebral infarction attributable to large artery stenosis or occlusion. The prognostic values and clinical characteristics of HVS remain to be elucidated. The aim of this study was to evaluate the association of HVS with ischemic lesions and severity of neurologic deficit. METHODS A total of 96 consecutive acute ischemic stroke patients (54 women, median age 76.5 [range 39-97] years), who had symptomatic severe stenosis or occlusion in the proximal middle cerebral artery that was detected with magnetic resonance angiography within 24 hours of onset, were enrolled. The extent of HVS was graded by a systematic quantitative scoring system (the HVS distribution score) based on Alberta Stroke Program Early Computed Tomographic Score. RESULTS An HVS was detected in 89 patients (93%) at admission, and the patients who displayed wider HVS distribution scores exhibited more severe neurologic deficits at admission (P<.05). The follow-up magnetic resonance imaging, which was obtained in 79 patients (82%), was performed an average of 13 days. The association between HVS distribution score and final ischemic lesions was strongly observed (n=67, P<.05) but not in the patients with intravenous thrombolysis (n=12, P=.06). CONCLUSIONS Although the distribution of HVS reflected final ischemic lesion, this association might not apply to the patients with the thrombolysis treatment. The interpretation of HVS distribution score with acute ischemic stroke patients should be discussed dependent on thrombolysis.

Leukocytes may have 2 opposing effects in intravenous rtPA treatment for ischemic stroke.

We hypothesized that leukocytes have 2 opposing effects on patients with ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Patients with ischemic stroke treated with rtPA were divided into 2 groups using the peripheral leukocyte count: high leukocyte group (HLG) and low leukocyte group (LLG) and were evaluated with the National Institutes of Health stroke scale (NIHSS) during the first 24 hours. We defined significant improvement (SI) as NIHSS improving by more than 50% from the baseline, and deterioration following improvement (DFI) as the achievement of SI within 24 hours but its subsequent loss at 24 hours. Fifty-three patients were enrolled, and the rate of SI within 24 hours was higher in HLG than in LLG (85.2% vs 42.3%, P = .0011). However, the rate of DFI was significantly higher in HLG than in LLG (29.6% vs 7.7%, P = .0413). We found that leukocytes might have not only deleterious but also beneficial effects in intravenous rtPA treatment.

Magnetic resonance spectroscopy after methanol poisoning

A 27‐year‐old Japanese man ingested methanol. He presented with reduced vision and lost consciousness after 2 days. He became comatose and developed metabolic acidosis, but improved and was discharged after 18 days. A brain magnetic resonance imaging–fluid attenuation inversion recovery sequence showed lesions in the putamen, caudate nucleus and subcortical white matter of both cerebral hemispheres. Magnetic resonance spectroscopy showed a low N‐acetylaspartate level, and high choline and lactic acid levels in the right putamen lesion, indicating that recovery coincided with symptom improvement. These magnetic resonance spectroscopy features might reflect the neuronal mitochondrial dysfunction and anaerobic glycolysis caused by the effect of formic acid, a metabolite of methanol.

Prevalences of Peripheral Arterial Disease Diagnosed by Computed Tomography Angiography in Patients with Acute Ischemic Stroke.

BACKGROUND Few studies have examined the prevalence of peripheral arterial disease (PAD) with the use of computed tomography angiography (CTA) in patients with acute ischemic stroke (AIS), although several reports have examined its prevalence using an ankle brachial index (ABI). We aimed to determine the prevalence of PAD indicated by CTA in patients with AIS and to clarify the prevalence of PAD in each clinical ischemic stroke subtype. METHODS We included 199 consecutive patients with AIS admitted to our hospital and divided them into PAD and non-PAD groups according to the CTA findings. RESULTS Of the 199 patients, 40 (20.1%) had PAD; 27 (67.5%) of the PAD patients were asymptomatic. The prevalence of abnormal ABI (≤.9) was 12.2%. Patients with PAD were older (78.3 ± 10.2 versus 71.5 ± 10.9, P <.001) and had a significantly lower ABI value (.89 ± .24 versus 1.15 ± .09, P <.001) and higher prevalence of diabetes mellitus (50.0% versus 31.4%, P = .028), atrial fibrillation (40.0% versus 16.4%, P = .001), coronary artery disease (32.5% versus 8.2%, P <.001), and intracranial arterial stenosis (47.5% versus 28.9%, P = .025) than patients without PAD. The prevalence of cerebral microbleeds was not different between patients with PAD and those without PAD (25.6% versus 25.4%, P = .985). The prevalence of PAD among ischemic stroke subtypes was highest in patients with cardioembolic infarction (40.5%). CONCLUSIONS Almost one fourth of the AIS patients examined had PAD on CTA. Cardioembolic infarction patients showed the highest prevalence of PAD among the clinical ischemic subtypes, suggesting the coexistence of atheromatous diseases and atrial fibrillation.