BACKGROUND: Noninvasive magnetic resonance angiography using ultra-high-field magnetic resonance imaging has recently provided us with the potential to image cerebral microvascular structures such as the lenticulostriate arteries. However, most studies using ultra-high-field magnetic resonance angiography have been limited to the visualisation of microvessels in healthy subjects, and the direct comparison of patients with microvascular disease has not been reported.

AIM: The aim of this study was to investigate the lenticulostriate arteries of patients with lacunar strokes of the basal ganglia and surrounding areas using 7?T magnetic resonance angiography.

METHODS: Ten stroke patients who had infarctions in the basal ganglia and adjacent areas detected using T2(*)-weighted images obtained from a conventional 1·5?T magnetic resonance imaging and 10 age-matched healthy subjects were recruited for this study. The large main vessels in the patient group were inspected to identify abnormalities such as stenosis. The characteristics of the lenticulostriate arteries visualised by 7?T magnetic resonance angiography, such as the number of branches and stems, curvature and tortuosity were analysed and compared between the patient and the control groups.

RESULTS: All patients had infarctions in the basal ganglia and adjacent regions, which were clearly determined by T2(*)-weighted images. However, there was no evidence of large-vessel abnormalities in the patient group. Analysis of 7?T magnetic resonance angiography data revealed that the overall number of lenticulostriate arteries branches in the patient group was significantly less than the control group (P=0·003). However, no statistical difference in the number of stems, curvature and tortuosity between the two groups was found (P=0·396, 0·258 and 0·888, respectively).

CONCLUSIONS: This study demonstrates that noninvasive magnetic resonance angiography using 7?T magnetic resonance imaging can visualise abnormalities in the cerebral microvasculature of stroke patients, and that the number of lenticulostriate arteries supplying the region of the basal ganglia is less in these patients compared with age-matched controls.

Some patients with anosognosia for hemiplegia, i.e. apparent unawareness of hemiplegia, have been clinically observed to show ‘tacit’ or ‘implicit’ awareness of their deficits. Here we have experimentally examined whether implicit and explicit responses to the same deficit-related material can dissociate. Fourteen stroke patients with right hemisphere lesions and contralesional paralysis were tested for implicit and explicit responses to brief sentences with deficit-related themes. These responses were elicited using: (i) a verbal inhibition test in which patients had to inhibit completing each sentence with an automatic response (implicit task) and (ii) a rating procedure in which patients rated the self-relevance of the same sentences (explicit task). A group of anosognosic hemiplegic patients was significantly slower than a control group of aware hemiplegic patients in performing the inhibition task with deficit-related sentences than with other emotionally negative themes (relative to neutral themes). This occurred despite their explicit denial of the self-relevance of the former sentences. Individual patient analysis showed that six of the seven anosognosic patients significantly differed from the control group in this dissociation. Using lesion mapping procedures, we found that the lesions of the anosognosic patients differed from those of the ‘aware’ controls mainly by involving the anterior parts of the insula, inferior motor areas, basal ganglia structures, limbic structures and deep white matter. In contrast, the anosognosic patient without implicit awareness had more cortical lesions, mostly in frontal areas, including lateral premotor regions, and also in the parietal and occipital lobes. These results provide strong experimental support for a specific dissociation between implicit and explicit awareness of deficits. More generally, the combination of our behavioural and neural findings suggests that an explicit, affectively personalized sensorimotor awareness requires the re-representation of sensorimotor information in the insular cortex, with possible involvement of limbic areas and basal ganglia circuits. The delusional features of anosognosia for hemiplegia can be explained as a failure of this re-representation.

BACKGROUND AND PURPOSE: Mural thickening and permeability changes in patients with amyloid angiopathy (CAA) and chronic hypertension are implicated in the pathophysiology of multiple, chronic subclinical microbleeds. The Spot sign, contrast extravasation on CT angiography, predicts hematoma expansion and is presumed to represent acute vessel damage. We hypothesize that the Spot sign is more common in patients without multiple prior chronic microbleeds.

METHODS: A retrospective study was conducted of 59 patients presenting within 6 hours of primary intracranial hemorrhage onset undergoing CT angiography and MRI. CT angiography spot sign presence was documented blinded to MRI. Hematoma expansion was defined as >6 mL or 30% enlargement. The Boston criteria were applied to microbleed interpretation dichotomizing subjects into probable and negative CAA. Basal ganglia, thalamic, and brain stem microbleed location were interpreted as chronic hypertensive pattern. Univariate logistic regression and ordinal logistic regression analysis identified significant predictive factors between spot-positive and -negative patients or microbleed pattern.

RESULTS: The incidence of spot positivity was 42%, 22%, and 0% for CAA-negative, chronic hypertensive, and CAA-positive patients, respectively (P=0.01). CAA-negative patients had higher baseline National Institutes of Health Stroke Scale (P=0.039), larger follow-up hematoma volume (P=0.02), and poorer Rankin score (P=0.049) than chronic hypertensive or CAA-positive patients. After age adjustment, spot-positive (P=0.023), age-related white matter change (P=0.041), number of microbleeds (P<0.0001), and modified Rankin score (P=0.027) remained significantly different between groups.

CONCLUSIONS: Boston criteria-defined CAA-negative status demonstrates the highest risk of spot positivity compared with patients with probable CAA and chronic hypertension.

Moyamoya disease is a rare stroke syndrome of unknown etiology resulting from stenosis or occlusion of the supraclinoid internal carotid artery (ICA) in association with an abnormal vascular network in the basal ganglia. Although the highest incidence of moyamoya disease is in pediatric patients, pathology reports have been primarily limited to adult samples and describe occlusive fibrocellular lesions in the intimae of affected arteries. We describe the case of a young girl with primary moyamoya disease who presented at 18 months of age with right hemiparesis following an ischemic stroke. Angiography showed stenosis of the distal left ICA, left middle cerebral artery, and right ICA. An emergent left-sided dural inversion was performed. Recurrent strokes and alternating hemiplegia necessitated a right dural inversion 6 months later. Nonetheless, her aggressive disease proved uniquely refractory to surgical revascularization, and she succumbed to recurrent strokes and neurological deterioration at 2.5 years of age. Pathological specimens revealed a striking bilateral occlusion of the anterior carotid circulation resulting from intimal proliferation of smooth muscle cells (SMCs). Most strikingly, the ascending aorta and the superior mesenteric artery demonstrated similar intimal proliferation, along with SMC proliferation in the media. The systemic pathology involving multiple arteries in this extremely young child, the first case of its kind available for autopsy, suggests that globally uncontrolled SMC proliferation, in the absence of environmental risk factors and likely resulting from an underlying genetic alteration, may be a primary etiologic event leading to moyamoya disease.

Changes in brain structure occur in remote regions following focal damage such as stroke. Such changes could disrupt processing of information across widely distributed brain networks. We used diffusion MRI tractography to assess connectivity between brain regions in 9 chronic stroke patients and 18 age-matched controls. We applied complex network analysis to calculate ‘communicability’, a measure of the ease with which information can travel across a network. Clustering individuals based on communicability separated patient and control groups, not only in the lesioned hemisphere but also in the contralesional hemisphere, despite the absence of gross structural pathology in the latter. In our highly selected patient group, lesions were localised to the left basal ganglia/internal capsule. We found reduced communicability in patients in regions surrounding the lesions in the affected hemisphere. In addition, communicability was reduced in homologous locations in the contralesional hemisphere for a subset of these regions. We interpret this as evidence for secondary degeneration of fibre pathways which occurs in remote regions interconnected, directly or indirectly, with the area of primary damage. We also identified regions with increased communicability in patients that could represent adaptive, plastic changes post-stroke. Network analysis provides new and powerful tools for understanding subtle changes in interactions across widely distributed brain networks following stroke.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrP(Sc)) induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI) showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI) resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG). Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrP(Sc).

BACKGROUND AND PURPOSE: Perfusion-weighted (PW) MRI is increasingly used to identify the tissue at risk. The adequate PW-MRI map and threshold remain controversial due to a considerable individual variation of values. By comparative positron emission tomography, we evaluated a simple MR-based and positron emission tomography-validated calibration of PW maps.

METHODS: PW-MRI and quantitative positron emission tomography (15O-water) of patients with acute stroke were used to calculate averaged as well as individual thresholds of penumbral flow (positron emission tomography cerebral blood flow (<20 mL/100 g/min) for maps of time to peak, mean transit time, cerebral blood flow, and cerebral blood volume. A linear regression analysis studied the variability of the individual thresholds using 3 different PW reference regions (hemispheric, white matter, gray matter). The best model was used for volumetric analysis to compare averaged and scaled individual thresholds and to calculate look-up tables for PW maps.

RESULTS: In 26 patients, the averaged thresholds were (median/interquartile range): cerebral blood flow 21.7 mL/100 g/min (19.9 to 32); cerebral blood volume 1.5 mL/100 g (0.9 to 1.8); mean transit time seconds 5.2 (3.9 to 6.9); and relative time to peak 4.2 seconds (2.8 to 5.8). The large individual variability was best explained by the mean value of the hemispheric reference derived from a region of interest on a level with the basal ganglia of the unaffected hemisphere (R(2): cerebral blood flow 0.76, cerebral blood volume 0.55, mean transit time 0.83, time to peak 0.95). Hemispheric reference-corrected thresholds clearly improved the detection of penumbral flow. Look-up tables were calculated to identify the individual thresholds according to the hemispheric reference value.

CONCLUSIONS: The individual variation of PW values, even if calculated by deconvolution, remains a major obstacle in quantitative PW imaging and can be significantly improved by a simple MR-based calibration. Easily applicable look-up tables identify the individual best threshold for each PW map to optimize mismatch detection.

Successful remembering involves both hindering irrelevant information from entering working memory (WM) and actively maintaining relevant information online. Using a voxelwise lesion-behavior brain mapping approach in stroke patients, we observed that lesions of the left basal ganglia render WM susceptible to irrelevant information. Lesions of the right prefrontal cortex on the other hand make it difficult to keep more than a few items in WM. These findings support basal ganglia-prefrontal cortex models of WM whereby the basal ganglia play a gatekeeper role and allow only relevant information to enter prefrontal cortex where this information then is actively maintained in WM.

BACKGROUND: Thrombus formation is a key step in the pathophysiology of acute ischemic stroke and results from the activation of the coagulation cascade. Thrombin plays a central role in this coagulation system and contributes to thrombus stability via activation of thrombin-activatable fibrinolysis inhibitor (TAFIa). TAFIa counteracts endogenous fibrinolysis at different stages and elevated TAFI levels are a risk factor for thrombotic events including ischemic stroke. Although substantial in vitro data on the influence of TAFI on the coagulation-fibrinolysis-system exist, investigations on the consequences of TAFI inhibition in animal models of cerebral ischemia are still lacking. In the present study we analyzed stroke development and post stroke functional outcome in TAFI-/- mice.

METHODOLOGY/PRINCIPAL FINDINGS: TAFI-/- mice and wild-type controls were subjected to 60 min transient middle cerebral artery occlusion (tMCAO) using the intraluminal filament method. After 24 hours, functional outcome scores were assessed and infarct volumes were measured from 2,3,5-Triphenyltetrazoliumchloride (TTC)-stained brain slices. Hematoxylin and eosin (H&E) staining was used to estimate the extent of neuronal cell damage. Thrombus formation within the infarcted brain areas was analyzed by immunoblot. Infarct volumes and functional outcomes did not significantly differ between TAFI-/- mice and controls (p>0.05). Histology revealed extensive ischemic neuronal damage regularly including the cortex and the basal ganglia in both groups. TAFI deficiency also had no influence on intracerebral fibrin(ogen) formation after tMCAO.

CONCLUSION: Our study shows that TAFI does not play a major role for thrombus formation and neuronal degeneration after ischemic brain challenge.

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims.