Akiko Hosomi

Characteristics of intracranial branch atheromatous disease and its association with progressive motor deficits

BACKGROUND 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. lipohyalinotic degenerative changes termed lipohyalinotic degeneration (LD). We herein analyze and describe the characteristics of these 2 different pathologies. METHODS We studied 394 patients with penetrating artery territory infarcts in the territories of the lenticulostriate arteries and anterior pontine arteries. Radiologically defined BAD of the lenticulostriate arteries was defined as infarcts with size more than 10mm in diameter on axial slice and visible for 3 or more axial slices, and that of the anterior pontine arteries was defined as unilateral infarcts extending to the basal surface of the pons. Within each of the 2 territory groups, differences between BAD and LD were compared. RESULTS Ninety five patients in the lenticulostriate arteries group (36.1%) and 78 patients in anterior pontine arteries group (59.5%) were classified as BAD. Initial NIHSS, incidence of progressive motor deficits and poor functional outcome were significantly higher and incidence of concomitant silent lacunar infarcts tended to be lower in BAD than LD. In logistic regression analysis, BAD compared with LD was independently associated with PMD, in lenticulostriate arteries group (OR: 4.21, p=0.0001) and in anterior pontine arteries group (OR: 5.32, p=0.0018). CONCLUSIONS Radiologically defined BAD and LD had different characteristics. BAD was significantly associated with progressive motor deficits and considered as a major vascular mechanism of progressive motor deficits in penetrating artery infarcts.

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.

Assessment of arcuate fasciculus with diffusion-tensor tractography may predict the prognosis of aphasia in patients with left middle cerebral artery infarcts

IntroductionIt is often clinically difficult to assess the severity of aphasia in the earliest stage of cerebral infarction. A method enabling objective assessment of verbal function is needed for this purpose. We examined whether diffusion tensor (DT) tractography is of clinical value in assessing aphasia.MethodsThirteen right-handed patients with left middle cerebral artery infarcts who were scanned within 2 days after stroke onset were enrolled in this study. Magnetic resonance data of ten control subjects were also examined by DT tractography. Based on the severity of aphasia at discharge, patients were divided into two groups: six patients in the aphasic group and seven in the nonaphasic group. Fractional anisotropy (FA) and number of arcuate fasciculus fibers were evaluated. Asymmetry index was calculated for both FA and number of fibers.ResultsFA values for the arcuate fasciculus fibers did not differ between hemispheres in either the patient groups or the controls. Number of arcuate fasciculus fibers exhibited a significant leftward asymmetry in the controls and the nonaphasic group but not in the aphasic group. Asymmetry index of number of fibers was significantly lower (rightward) in the aphasic group than in the nonaphasic (P = 0.015) and control (P = 0.005) groups. Loss of leftward asymmetry in number of AF fibers predicted aphasia at discharge with a sensitivity of 0.83 and specificity of 0.86.ConclusionsAsymmetry of arcuate fasciculus fibers by DT tractography may deserve to be assessed in acute infarction for predicting the fate of vascular aphasia.

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.

Predictive Markers of Blood Cytokine and Chemokine in Recurrent Brain Infarction

The mechanism of the inflammatory response in the vascular wall in atherothrombosis and during the progression of atherosclerosis has attracted attention. We focused on the potential usefulness of inflammatory markers in chronic recurrent brain infarction, and analyzed the role of inflammatory markers in atherosclerosis of the intracranial artery. The subjects were 2 groups of patients treated between 2004 and 2006: a group of outpatients with recurrent infarction (group RI), who developed atherothrombotic brain infarction twice; another group of outpatients with brain infarction without recurrence (group BI), who developed brain infarction once and remained free of recurrence for >1 year; and a group of control subjects with normal brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) (group C). Plasma samples were collected from each group of patients for the simultaneous measurement of 17 kinds of candidate inflammatory markers, using a fluorescent microbead array system, and the results were compared with head MRA findings. The levels of high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in group RI patients than in groups C and BI. Subjects with a hsCRP level > or =0.3 and a MCP-1 level > or =200 in the serum have, respectively, a 1.92 and 2.98 relative risk to have a potential recurrent infarction. Regarding the relation of inflammatory marker levels with MRA findings, group RI showed significantly higher levels of hsCRP at M1 lesions and MCP-1 at A1 and M1 lesions than group BI (P < 0.05). In conclusion, the MCP-1 level as well as hsCRP in the blood can be a potential predictive marker of recurrent thrombotic brain infarction, and may reflect inflammation that promotes intracranial large-artery atherosclerosis.

Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine.

A 64-year-old woman was admitted to our hospital for recurrent stroke and cognitive impairment and was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Iodine-123 iodoamphetamine single photon emission computed tomography showed hypoperfusion in the whole brain, but cerebral blood flow increased dramatically after the administration of acetazolamide in the cerebral cortex. Lomerizine, a diphenylmethylpiperazine Ca2+ channel blocker, can selectively increase cerebral blood flow. Cognitive decline and cerebral hypoperfusion improved during 2-year administration of lomerizine in this CADASIL patient, and thus, lomerizine is a potential candidate for treating cognitive impairment in CADASIL patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): A patient from Sri Lanka

We report the first patient from Sri Lanka (the third patient from the Indian subcontinent) with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The patient experienced a young onset familial stroke with an 856T>G missense mutation in exon 5 of the NOTCH3 gene resulting in a C260G mutation in the sixth epidermal growth factor-like repeat. We believe this is the first reported Sri Lankan patient. CADASIL is probably underdiagnosed in the region.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), first reported case from Sri Lanka

Disrupted-In-Schizophrenia (DISC1) is a candidate susceptibility gene for major psychiatric diseases including schizophrenia, depression and bipolar disorder, while biological roles of the DISC1 protein have not yet been fully explained. In the present study, a 129 substrain-specific 25-bp deletion in exon 6 of Disc1 that introduces a termination codon at exon 7 and abolishes production of the full-length protein was transferred to the C57BL/6J genetic background. We used behavioral assays to assess Disc1-deficient mice for depression-like behaviors. Immobility time in the forced swimming test and the tail suspension test was comparable between wildtype and Disc1-null mice. Brain sections of Disc1-deficient mice were examined in the microscopy. Gross brain morphology appeared normal in Disc1-null mice. Immunofluorescent staining was performed to compare the expression pattern of DISC1-related proteins in wild-type and Disc1-deficient mice. Further analysis of mice carrying the 129 substrain-derived deletion variant might help to explain how DISC1 variation contributes to susceptibility in humans.