How Topographic Diffusion-Weighted Imaging Patterns can Predict the Potential Embolic Source.

PURPOSE: To develop an imaging prediction model for patients with embolic stroke of undetermined source (ESUS), we investigated the association of topographic diffusion-weighted imaging (DWI) patterns with potential embolic sources (PES) identified by transesophageal echocardiography. METHODS: From a total of 992 consecutive patients with embolic stroke, 366 patients with the ESUS group were selected. ESUS was defined as no atrial fibrillation (Af) within 24h from admission and no PES after general examination. Clinical variables include age (> 80years, 70-80 years), sex, vascular risk factors and left atrial diameter > 4 cm. Age, sex and vascular risk factors adjusted odds ratio of each DWI for the different PESs were calculated. DWI was determined based on the arterial territories. Middle cerebral arteries were divided into 4 segments, i.e., M1-M4. Moreover, M2 segments were subdivided into superior and inferior branches. RESULTS: The 366 patients consisted of 168 with paroxysmal Af (pAf), 77 with paradoxical embolism, 71 with aortic embolism and 50 with undetermined embolism after transesophageal echocardiography. The variables adjusted odds ratio (OR) of internal carotid artery (OR: 12.1, p = 0.037), M1 (4.2, p = 0.001), inferior M2 (7.5, p = 0.0041) and multiple cortical branches (12.6, p < 0.0001) were significantly higher in patients with pAf. Striatocapsular infarction (12.5, p < 0.0001) and posterior inferior cerebellar artery infarcts (3.6, p = 0.018) were significantly associated with paradoxical embolism. Clinical variables adjusted OR of multiple small scattered infarcts (8.3, p < 0.0001) were significantly higher in patients with aortic embolism. CONCLUSION: The associations of DWI with different PES have their distinctive characteristics and DWI along with clinical variables may help predict PES in patients with ESUS.

Long insular artery infarction: characteristics of a previously unrecognized entity.

BACKGROUND AND PURPOSE: The infarctions arising in the long insular arteries of the M2 segment have been poorly described in the past. The purpose of this study was to investigate the incidence, clinical characteristics, and pathogenesis of long insular artery infarcts. MATERIALS AND METHODS: Patients with acute isolated infarcts in territories of the long insular arteries and lenticulostriate arteries were retrospectively reviewed. The long insular artery territory was defined as the area above the lenticulostriate artery territory at the level of centrum semiovale. On the coronal section, it lies between the tip of the anterior horn and the top of the superior limb of the insular cleft. Clinical features and prevalence of embolic sources were compared between the 2 groups. RESULTS: Of 356 consecutive patients with acute ischemic stroke, 8 (2.2%) had a long insular artery infarct (long insular artery group) and 50 (14.0%) had a lenticulostriate artery infarct (lenticulostriate artery group). There were no differences in age, sex, prevalence of risk factors, neurologic deficit, or incidence of lacunar syndromes between these groups. Abrupt onset was more common in the long insular artery than in the lenticulostriate artery group (P = .004). The prevalence of embolic high-risk sources (eg, atrial fibrillation) was not significantly different between these groups, but the combined prevalence of all embolic sources, including moderate-risk sources, was significantly higher in the long insular artery group (P = .048). CONCLUSIONS: Isolated infarction caused by long insular artery occlusion is not rare. Abrupt onset is more common for long insular artery infarction, and this finding could be attributed to the higher incidence of an embolic etiology as the pathogenesis of infarction.

Low vitamin and carotenoid levels are related to cerebral white matter lesions.

PURPOSE: To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. SUBJECTS AND METHODS: Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. RESULTS: Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking. CONCLUSION: Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch.

OBJECTIVE: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. METHODS: EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. RESULTS: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. CONCLUSIONS: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.

Diffusion tensor imaging may help the determination of time at onset in cerebral ischaemia.

BACKGROUND AND AIMS: The apparent diffusion coefficient (ADC) and anisotropy (eg, fractional anisotropy (FA)) of ischaemic tissue evolve over time. A reduction in diffusivity (ie, lambda(2) and lambda(3)) is an important marker for characterising hyperacute-stage infarction, as these parameters may reflect axonal membrane status. The study examines whether transverse diffusivity could be useful in assessing white matter infarcts of various ages. METHODS: Diffusion tensor imaging data from 44 adult patients (34 men, 10 women, aged 46 to 89 years, mean = 70.3) with acute white matter infarction (1-168 h) of the internal capsule were analysed. Relative eigenvalues were calculated as: (lambda(ipsi)-lambda(contra))/lambda(contra). Lesions were classified based on theoretically expected evolution of diffusivity over time as follows: stage I, FA higher than the contralesional region of interest (ROI); stage II, diffusivity lower than the contralesional side for all eigenvalues; stage III, one of two transverse eigenvalues (lambda(2) or lambda(3)) higher than the contralesional ROI. RESULTS: Stage I infarcts (n = 5) were found primarily within 24 h of the onset of symptoms, with one case found on the third day. Stage II infarcts were found most commonly within 24 h (n = 18), and fewer after 24 h. After the first day, the ratio of stage III infarcts increased significantly. Thus, diffusivity-based classification of white matter infarcts seems to show a chronological trend. CONCLUSIONS: Diffusion anisotropy may be useful for defining the biological tissue clock of white matter infarctions.

Incidental acute infarcts identified on diffusion-weighted images: a university hospital-based study.

BACKGROUND AND PURPOSE: Pathogenesis of leukoaraiosis is incompletely understood and accumulation of small infarctions may be one of the possible sources of such white matter lesions. Thus, the purpose of this study was to identify the rate of incident infarction as depicted on diffusion-weighted images (DWIs) obtained from a general patient population. MATERIALS AND METHODS: During the 4-year study period, a total of 60 patients (36 men and 24 women) had an incidental DWI-defined infarction without overt clinical symptoms suggestive of a stroke or a transient ischemic attack. All of the MR images were obtained by using a similar protocol on 2 identical 1.5T whole-body scanners. The patient's vascular risk factors, as well as the presence of white matter lesions (WMLs) on MR imaging and atheromatous changes on MR angiography, were assessed retrospectively. The incidental DWI-defined infarcts were also characterized in terms of their lateralization, lobe, and specific location. RESULTS: A total of 16,206 consecutive brain MR images were done during the study period; the overall incidence of incidental infarcts was 0.37%. Most of these patients with an incidental infarct had vascular risk factors and WMLs on MR images. Most of these patients (80%) had a single lesion on DWI. A total of 88 lesions were identified; most were located in the white matter of the supratentorial brain, primarily in the frontoparietal lobes. There were also lesions involving the brain stem (n = 2). The lesions involving cerebrum were more commonly located in the right side (right to left = 52:34). CONCLUSION: Small, DWI-defined acute brain infarctions can be found incidentally in an asymptomatic population; this finding may account, at least in part, for the pathogenesis of WMLs identified on MR imaging.

Acetazolamide vasoreactivity evaluated by transcranial power harmonic imaging and Doppler sonography.

BACKGROUND: Cerebral vasoreactivity (CVR) in the major cerebral arteries evaluated by transcranial Doppler sonography has shown some correlation with CVR in the brain tissue measured by other neuroradiological modalities. To clarify vasoreactive differences in the brain tissue and the major cerebral arteries, we have evaluated the relationship of acetazolamide (ACZ) CVR between transcranial ultrasonic power harmonic imaging (PHI) and color Doppler sonography (CDS), in cases ofparenchymal pathology with and without occlusive vascular lesions. MATERIALS AND METHODS: The subjects were 31 stroke patients with intraparenchymal pathologies, 15 with (occlusive group) and 16 without (non-occlusive group) occlusive carotid and/or middle cerebral artery lesions. CVR based on values before/after ACZ (angle-collected CDS velocity in the middle and posterior cerebral arteries, PHI contrast area size, peak intensity, time to peak intensity), and correlation of CVR between PHI and CDS were compared between the side with and without lesions in both groups. FINDINGS: (a) PHI CVR tended to be more disturbed than CDS CVR. CVR side differences were not significant. (b) CVR correlations between PHI and CDS were always lower in the pathological sides. CONCLUSIONS: CVR in brain tissue evaluated by PHI is susceptible to disturbance in comparison with CDS, due to both parenchymal and vascular occlusive pathologies.

Losartan, an angiotensin II (AT1) receptor antagonist, preserves cerebral blood flow in hypertensive patients with a history of stroke.

In patients with severe hypertension, chronic heart failure or a history of stroke, the lower limit of autoregulation of cerebral blood flow (CBF) is shifted to higher levels of blood pressure (BP) than those observed in healthy subjects. The aim of pharmacotherapy for hypertensive patients with an impaired autoregulation of CBF should be to reduce BP while preserving an appropriate CBF. In the present study, 16 hypertensive patients who had had an episode of stroke more than 4 weeks previously were administered the angiotensin II (AT1) receptor antagonist losartan at daily doses of 25-100 mg for 4 weeks. Systolic and diastolic blood pressures were recorded for 24 h using an ambulatory BP monitoring system. CBF in both hemispheres of the cerebrum and cerebellum was quantified using single photon emission tomography with N-isopropyl-p-[123I]iodoamphetamine. At baseline, CBF was 29.7 +/- 6.7 ml/min/100 g in the cerebrum and 31.5 +/- 7.5 ml/min/100 g in the cerebellum. At the end of treatment, BP was lower, while CBF increased by 7.7% in the cerebrum, and remained at the baseline level in the cerebellum. Thus, CBF was preserved despite the reduction in BP. We consider the use of losartan is advantageous for hypertensive patients with a history of stroke in whom autoregulation of CBF is potentially impaired.

[Peripheral neuropathy involving cranial nerves in a patient with hepatitis C virus infection and mixed cryoglobulinemia].

A 75-year-old man developed subacute progressive muscle weakness and painful paresthesia of the left upper and right lower limbs. The patient had no history of diabetes mellitus. On physical examination, there was no evidence of icterus or hepatosplenomegaly. Palmar erythema without rash was noted. Neurologic examination revealed muscle atrophy and weakness in the left upper limb and mild muscle weakness in the right proximal lower limb. Dysesthesia, severe hypesthesia, and hypalgesia were found in the left upper limb. The tendon reflexes were decreased in the left upper limb and absent in the lower limbs. The cranial nerves were preserved on the day of admission, followed by the involvement of the right oculomotor nerve. Serological examination revealed a mixed IgG/IgM cryoglobulinemia and hepatitis C virus (HCV) infection with evidence of HCV virus replication by PCR for HCV RNA. The patient was diagnosed as having a mixed cryoglobulinemic neuropathy associated with HCV infection. Interferon-alpha therapy with 3 million units subcutaneously was initiated three times per week; however, there was no clinical improvement, although cryoglobulins became undetectable and the level of serum HCV RNA decreased remarkably. Intravenous immunoglobulin therapy 20 g per day for 5 days was also ineffective. The patient developed right facial nerve palsy, followed by right abducens nerve palsy. Treatment with prednisolone 40 mg per day improved and stabilized neurologic symptoms. Although interferon-alpha is considered to be a promising therapy for neurologic complications of HCV infection with mixed cryoglobulinemia, the optimal treatment remains unestablished.