Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: structural MR imaging changes and apolipoprotein E genotype

BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) genotype plays an important role in the development, maintenance, and response to injury of the central nervous system. It has been suggested that apoE epsilon4 genotype is a risk factor for several neurologic disorders. We investigated the correlation between the apoE genotype and radiologic data in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: T1-weighted, dual fast spin-echo, T2*-weighted gradient echo, and fluid-attenuated inversion recovery MR imaging scans were obtained from 36 CADASIL patients (21-59 years of age). The number of lacunar infarcts and microbleeds and the presence of subcortical lacunar lesions were determined. The amount of white matter hyperintensities was assessed by using semiautomated segmentation software. The relation between the radiologic endophenotype of CADASIL and the apoE genotype was assessed by using a Student t test for unpaired data and Fisher exact test. RESULTS: White matter hyperintensities, lacunar infarcts, microbleeds, and subcortical lacunar lesions were not found to be associated with the presence of an epsilon4 allele. CONCLUSION: The variability of structural MR imaging lesions in CADASIL is independent of apoE genotype and other processes must underlie the variable natural history of the disease.     

Subcortical lacunar lesions: an MR imaging finding in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

PURPOSE: To assess the prevalence and distribution of subcortical lacunar lesions (SLLs) in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to determine whether SLLs are an abnormal finding by studying their prevalence in healthy subjects, and to assess whether SLLs occur in other conditions associated with small vessel disease and white matter areas of high signal intensity (WMH). MATERIALS AND METHODS: The presence of SLLs, their location, and their relation to other abnormalities were assessed on magnetic resonance (MR) images (T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery) obtained in 34 CADASIL patients and 20 healthy family members. Three additional control groups of healthy volunteers, elderly patients with vascular risk factors, and patients with another hereditary small vessel disease were also screened for the presence and location of SLLs. Sensitivity and specificity of the presence of SLLs for the diagnosis of CADASIL were assessed. RESULTS: SLLs were found in 20 (59%) of CADASIL patients. Incidence of SLLs increased with age (20%, <30 years; 50%, 30-50 years; 80%, >50 years). SLLs invariably occurred in the anterior temporal lobes and in areas where diffuse WMH expanded into arcuate fibers. From the anterior temporal lobe, the lesions could extend dorsally into the temporal lobes and rostrally into the frontal lobes. Lesions were not found in the parietal and occipital lobes. None of the control subjects had SLLs. Specificity and sensitivity of SLLs for CADASIL were 100% and 59%, respectively. CONCLUSION: SLLs are an abnormal finding at MR imaging that frequently occur in CADASIL patients.     

MR and CT of lacunar infarcts

Twenty-two patients with clinical signs and symptoms compatible with lacunar transient ischemic attack or stroke of varying chronicity were evaluated with MR imaging. CT was also performed in 21 of these patients. MR revealed small, deep cerebral lesions in locations appropriate to the clinical symptoms in 19 patients. Lacunar infarcts were imaged by CT in 11 patients; however, no lesions were identified on CT that were not detected with MR. Presumed lacunar infarcts were identified on MR images in 17 additional patients. Lacunae generally appeared as focal areas of decreased signal intensity on T1-weighted images and as focal areas of increased signal intensity on T2-weighted images. T2-weighted MR images detected a greater number of lacunar infarcts than did mixed T1-/T2-weighted images, which in turn detected more lacunae than did T1-weighted images. In general, acute lacunar infarcts (within 1 week of onset or recurrence of clinical symptoms) were seen only on T2-weighted images, while chronic lesions (more than 1 week) were seen on both T1- and T2-weighted images. Our results indicate that MR is superior to CT for evaluating lacunar infarcts, and second, that T2-weighted images are more sensitive than T1- and mixed T1-/T2-weighted images for detecting lacunar infarcts.     

常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病的颅脑MRI表现

目的 提高对常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病(CADASIL)的颅脑MRI表现的认识.方法 对一家系2代5例患者进行头颅常规MR和MR血管成像(MRA)检查.对经Notch3基因检查或皮肤组织活检超微病理检查确诊的3例和经MRI与临床诊断的1例CADASIL的MRI资料进行分析.结果 MR检查的5例中4例CADASIL均获得明确诊断,1例排除诊断.4例CADASIL均见两侧颞叶、额叶和顶叶大致对称性皮层下与侧脑室旁白质病灶,呈长T1、长T2信号,但枕叶累及甚少且皮层不受累;O'Sullivan征阳性4例,皮层下腔隙性损害(SLLs)征阳性2例;3例半卵圆中心可见多发圆形或卵圆形囊性梗死即"黑洞",4例均见多发圆点状血管周间隙即"胡椒罐盖"样征象;4例全部显示胼胝体单发或多发斑片状显著长T1、长T2信号,其中2例伴萎缩;内囊前肢与外囊均受累,呈"人"字征;基底节和脑干可见单发或多发陈旧性腔隙性梗死灶;1例伴右侧小脑小片状梗死灶;4例全部有轻度至中度的脑干、小脑和大脑萎缩;MRA颅内Ⅰ-Ⅲ级较大动脉均未见明显异常.结论 CADASIL的颅脑MRI表现具有一定的特征性,可为CADASIL的初诊和筛选提供重要依据.     

Human brain infarcts: Gd-DTPA-enhanced MR imaging

During Food and Drug Administration phase II and III clinical trials for gadolinium DTPA, the paramagnetic agent was used to study 11 patients with 20 subacute and chronic cerebral infarcts. Five patients had numerous periventricular and deep white-matter lesions, probably due to chronic ischemic disease. Magnetic resonance (MR) imaging was performed 4-30 days after the ictus, preceded by computed tomography (CT) in all but one case. In most cases, the nonenhanced spin-echo (SE) images, obtained at 500-msec repetition times and 30-msec echo times, failed to demonstrate the infarct, and in general the gadolinium-enhanced SE 500/30 images matched the contrast material-enhanced CT scans in pattern. Periventricular lesions and small, deep, white-matter infarcts that were chronic and asymptomatic were not enhanced by gadolinium MR. However, three small, symptomatic capsular and brain-stem infarcts showed definite enhancement. Usually the enhancement was visible at 3 minutes, increasing to a peak at 30 minutes. At 55 minutes, the enhancement increased in the medium-aged infarcts (8-14 days), while it decreased in the late infarcts (15-30 days). The T2 relaxation time-weighted pulse sequences were most sensitive for demonstrating all infarcts, but without the aid of a contrast agent, they were frequently poor in specificity.     

The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a condition causing recurrent subcortical strokes. MR imaging, which shows focal lacunar infarcts and leukoaraiosis, plays a central role in the diagnosis and evaluation. We studied MR imaging abnormalities in a large prospectively recruited cohort of CADASIL patients to describe the spatial distribution of abnormalities, determine how this distribution alters with age, and identify any correlations with the clinical features of the disease. METHODS: In this study, 112 CADASIL subjects from 64 families were prospectively recruited. MR imaging scans were graded by a single neuroradiologist, by using the modified Scheltens scale, to quantify the severity of high-signal-intensity changes in different brain regions. RESULTS: Lesion load increased progressively with age. Scores were maximal in the frontal, parietal, and anterior temporal cortex, and the external capsule; intermediate in the pons; and relatively low in the corpus callosum, caudate, globus pallidus, cerebellum, midbrain, and medulla. Anterior temporal pole involvement was common at all ages and, when present, usually confluent, but this was absent in 33% of patients 20-29 years of age. A history of stroke correlated with total Scheltens score and internal capsule and pontine scores. Dementia correlated with total Scheltens score and subcortical white matter score, whereas depression correlated with subcortical white matter score but not total Scheltens score. CONCLUSIONS: There is a characteristic pattern of MR imaging abnormalities in CADASIL that aids in differential diagnosis; however, some characteristic features, such as anterior temporal pole involvement, can be absent. MR imaging lesion load correlated with some clinical features including stroke and dementia, whereas depression is more common in individuals with deep white matter changes.     

The value of b required to avoid T2 shine-through from old lucunar infarcts in diffusion-weighted imaging

Multiple small infarcts of different ages are common in small-vessel disease. Diffusion-weighted imaging (DWI) is a powerful method for discriminating new from chronic lesions. This can be done on the diffusion-weighted images provided that b is sufficiently high. Our purpose was to determine that critical value of b. We reviewed DWI from a previous study of acute, mainly lacunar strokes, and selected 18 old lacunar infarcts, well defined on uncoded images with b 0 s/m² (i. e., T2-weighted images) but invisible on DWI with b 1200 × 10⁶ s/m². We used a 1.5 tesla imager and single-shot echo-planar technique. We had seven separate acquisitions with echo time 123 ms and b in steps between 0 and 1200 × 10⁶ s/m². Two neuroradiologists blinded to the selection of lesions carried out two different lesion-detection procedures, thereby testing each lesion four times, giving a total of 72 tests of b values. The results were consistent, indicating a level for detection of 800 × 10⁶ s/m² in two tests, 400–600 × 10⁶ s/m² in 65 tests and at lower values in the remainder. For imagers up to 1.5 tesla, at long repetition times and an echo time up to 120 ms T2-shine through of old lacunar infarcts can be avoided using b of 1000 × 10⁶ s/m². Received: 5 July 2000 Accepted: 6 December 2000     

Persistent high signal on diffusion-weighted MRI in the late stages of small cortical and lacunar ischaemic lesions

Diffusion-weighted imaging (DWI) is very sensitive to early brain infarcts. However, the late stages have been insufficiently studied. Infarcts in small vessel disease are often multiple and of different ages, and differentiation between new and old lesions might be difficult. We have therefore studied the change with time in DWI of small (< 3 ml) ischaemic lesions. We imaged 21 patients with an acute lacunar syndrome and a lesion visible on early DWI. They all had three MRI examinations 12-58 h (early), 7-16 and 54-144 days after the onset of stroke; 10 patients with high DWI signal on the third examination had a fourth examination 12-28 months after the stroke. MRI was performed at 1.5 T, using echo-planar DWI with 7 b-values from 0 to 1200 x 10(6) s/m2 and conventional T2-weighted imaging. After 7-16 days 18 of 21 lesions gave high signal on DWI, and 12/16 measurable lesions had a decreased apparent diffusion coefficient (ADC). After 54-144 days ten lesions still gave high DWI signal and two still had an ADC below normal. On the fourth examination there was no remaining high DWI signal and all ADC were higher than normal.     

Detection of clinically silent infarcts after carotid endarterectomy by use of diffusion-weighted imaging

BACKGROUND AND PURPOSE: Intraprocedural transcranial Doppler sonography has identified multiple microembolic events during and immediately after carotid endarterectomy (CEA) or angioplasty, yet the rate of clinically evident stroke is small. To determine the significance of the transcranial Doppler sonography findings, we examined patients by use of diffusion-weighted imaging and fluid-attenuated inversion recovery MR imaging before and immediately after CEA for evidence of clinically silent ischemic events. METHODS: Twenty-five patients with atherosclerotic disease of the carotid arteries underwent diffusion-weighted imaging and fluid-attenuated inversion recovery MR imaging performed, on average, 3 days before and 12 hours after CEA. Diffusion-weighted images were acquired in three orthogonal directions at b = 900. Pre- and postoperative neurologic examinations were performed by the same physician. RESULTS: After endarterectomy, 4.0% of the patients (one of 25 patients) showed a single, cortical focus of restricted diffusion and new fluid-attenuated inversion recovery hyperintensity, measuring <1 cm in diameter, ipsilateral to the CEA. The postoperative neurologic examination showed no change in status from the preoperative baseline state. This patient had an intraoperative course complicated by the development of a large luminal thrombus, necessitating thrombectomy. CONCLUSION: The use of diffusion-weighted imaging may serve to improve conspicuity of clinically silent infarcts after CEA. An important next step is to determine the risk factors that predispose to detectable parenchymal ischemic events.     

Differentiation of recent and old cerebral infarcts by diffusion-weighted MRI

We performed MRI, including diffusion-weighted imaging, in 15 patients with recurrent strokes with acute ischaemia and at least one old lesion according to the clinical history and/or CT. Routine MRI showed similar signal intensity changes in both situations. Diffusion-weighted images, however, were positive in all acute or subacute infarcts. The high signal of acutely disturbed diffusion due to intracellular oedema could also be identified in small brain stem lesions. Spatial resolution was increased by applying separate gradients in each axis instead of creating anisotropy-independent trace images. Received: 17 September 1997 Accepted: 6 April 1998     

Distribution territories and causative mechanisms of ischemic stroke

Ischemic stroke prognosis, risk of recurrence, clinical assessment, and treatment decisions are influenced by stroke subtype (anatomic distribution and causative mechanism of infarction). Stroke subtype diagnosis is better achieved in the early phase of acute ischemia with the use of multimodal MR imaging. The pattern of brain lesions as shown by brain MR imaging can be classified according to a modified Oxfordshire method, based on the anatomic distribution of the infarcts into six groups: (1) total anterior circulation infarcts, (2) partial anterior circulation infarcts, (3) posterior circulation infarcts, (4) watershed infarcts, (5) centrum ovale infarcts, and (6) lacunar infarcts. The subtype of stroke according to its causative mechanism is based on the TOAST method, which classifies stroke into five major etiologic groups: (1) large-vessel atherosclerotic disease, (2) small-vessel atherosclerotic disease, (3) cardioembolic source, (4) other determined etiologies, and (5) undetermined or multiple possible etiologies. The different MR imaging patterns of acute ischemic brain lesions visualized using diffusion-weighted imaging and the pattern of vessel involvement demonstrated with MR angiography are essential factors that can suggest the most likely causative mechanism of infarction. This information may have an impact on decisions regarding therapy and the performance of additional diagnostic tests.     

Computer-aided diagnosis scheme for detection of lacunar infarcts on MR images

RATIONALE AND OBJECTIVES: The detection and management of asymptomatic lacunar infarcts on magnetic resonance (MR) images are important tasks for radiologists to ensure the prevention of severe cerebral infarctions. However, accurate identification of the lacunar infarcts on MR images is a difficult task for the radiologists. Therefore the purpose of this study was to develop a computer-aided diagnosis scheme for the detection of lacunar infarcts to assist radiologists' interpretation as a "second opinion." MATERIALS AND METHODS: Our database comprised 1,143 T1- and 1,143 T2-weighted images obtained from 132 patients. The locations of the lacunar infarcts were determined by experienced neuroradiologists. We first segmented the cerebral region in a T1-weighted image by using a region growing technique for restricting the search area of lacunar infarcts. For identifying the initial lacunar infarcts candidates, a top-hat transform and multiple-phase binarization were then applied to the T2-weighted image within the segmented cerebral region. For eliminating the false positives (FPs), we determined 12 features--the locations x and y, signal intensity differences in the T1- and T2-weighted images, nodular components from a scale of 1 to 4, and nodular and linear components from a scale of 1 to 4. The nodular components and the linear components were obtained using a filter bank technique. The rule-based schemes and a support vector machine with 12 features were applied to the regions of the initial candidates for distinguishing between lacunar infarcts and FPs. RESULTS: Our computerized scheme was evaluated by using a holdout method. The sensitivity of the detection of lacunar infarcts was 96.8% (90/93) with 0.76 FP per image. CONCLUSIONS: Our computerized scheme would be useful in assisting radiologists for identifying lacunar infarcts in MR images.     

Diffusion-weighted echo-planar MRI of lacunar infarcts

We studied 35 patients with lacunar infarcts, using diffusion-weighted echo-planar imaging (DW-EPI) at 1.5 T. The relative apparent diffusion coefficient ratio (ADCR) of each lesion was calculated and lesion conspicuity on DW-EPI was compared to that on images aquired with fast fluid-attenuated inversion recovery and T2-weighted fast spin-echo sequences. Acute small infarcts (within 3 days) were identified with DW-EPI as an area of decreased ADCR (range 0.33–0.87; mean 0.67) and high signal, subacute small infarcts (4–30 days) as a high-signal or isointense areas of decreased or nearly normal ADCR (0.54–0.98; 0.73), and chronic small infarcts (> 30 days) as low- or high-signal areas of nearly normal or increased ADCR (0.97–1.92; 1.32). In three patients, small infarcts of the brain stem in the hyperacute phase (within 6 h) were seen only with DW-EPI. In five patients, fresh small infarcts adjacent to multiple old infarcts could be distinguished only with DW-EPI. Received: 22 September 1997 Accepted: 25 November 1997     

Border zone infarcts: pathophysiologic and imaging characteristics

Border zone or watershed infarcts are ischemic lesions that occur in characteristic locations at the junction between two main arterial territories. These lesions constitute approximately 10% of all brain infarcts and are well described in the literature. Their pathophysiology has not yet been fully elucidated, but a commonly accepted hypothesis holds that decreased perfusion in the distal regions of the vascular territories leaves them vulnerable to infarction. Two types of border zone infarcts are recognized: external (cortical) and internal (subcortical). To select the most appropriate methods for managing these infarcts, it is important to understand the underlying causal mechanisms. Internal border zone infarcts are caused mainly by hemodynamic compromise, whereas external border zone infarcts are believed to result from embolism but not always with associated hypoperfusion. Various imaging modalities have been used to determine the presence and extent of hemodynamic compromise or misery perfusion in association with border zone infarcts, and some findings (eg, multiple small internal infarcts) have proved to be independent predictors of subsequent ischemic stroke. A combination of several advanced techniques (eg, diffusion and perfusion magnetic resonance imaging and computed tomography, positron emission tomography, transcranial Doppler ultrasonography) can be useful for identifying the pathophysiologic process, making an early clinical diagnosis, guiding management, and predicting the outcome.     

Repeated computed tomography in lacunar infarcts of the brain

This prospective and consecutive study of 74 patients with completed stroke elucidates occurrence, localization and evolution of lacunar infarcts on repeated CT examinations. Twenty patients had large infarcts (diameter greater than 3 cm), 25 medium-sized infarcts (diameter greater than or equal to 1.5 cm - less than or equal to 3 cm), and 16 had lacunar infarcts (diameter less than 1.5 cm). In 13 patients no infarct was seen. The lacunar infarcts were characterized by delayed appearance on CT, low incidence of fog effect, and infrequent presence of contrast enhancement. In 9 of the 16 patients (56%) the lacunar infarct could be identified on the first CT, performed approximately 3 days after the stroke. In 2 patients the infarct was first revealed on the second (2 weeks post stroke) and in 5 on the third CT (6 months post stroke). The delayed appearance might be due to a partial volume effect. Early development of fog effect may also be considered. As contrast enhancement was observed in only 8 per cent of the patients with lacunar infarcts on CT, and in 70 per cent of the entire group of patients in our series with ischemic infarcts, contrast enhancement seemed to be a function of lesion size.     

Distribution of cranial MRI abnormalities in patients with symptomatic and subclinical CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited cause of early stroke and dementia, with a poor prognosis. This study was performed to clarify lesion appearance and pattern of lesion distribution in CADASIL. 20 members of a single family were tested for the CADASIL gene mutation and studied with cranial MRI. Scans were evaluated for lesion load and pattern of lesion distribution. 19 patients had cranial MRI, of whom 11 had normal MRI scans, were clinically unaffected and tested negative for the CADASIL gene mutation. The remaining eight patients had abnormal cranial MRI scans: seven patients were positive for the CADASIL gene mutation and one (untested) patient was severely clinically affected. Three of the patients who tested positive for the CADASIL gene mutation were clinically unaffected at the time of imaging. All eight patients with abnormal cranial MRI had subcortical white matter abnormalities, mostly in frontal and temporal lobes. Lesions involving the corpus callosum were present on sagittal T2 weighted images in four of five clinically affected and one of three clinically unaffected patients. Lesions involving the deep grey nuclei and the brain stem were common. On T1 weighted images, lesions were either poorly defined (confluent white matter hypointensity) or well defined (cystic infarcts or enlarged perivascular spaces). Atrophy was infrequent. Familiarity with the range of cranial MRI appearances may aid diagnosis of CADASIL. Recognition of cranial imaging features in asymptomatic CADASIL patients could prompt earlier diagnosis.     

Assessment of cerebral hemodynamics to acetazolamide using brain perfusion SPECT in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy caused by mutations in the Notch3 gene located on chromosome 19, leading to 4 cardinal features with aura, cerebrovascular ischemic events, mood disturbances, and dementia. Acetazolamide (ACZ) has been promoted as a drug to determine cerebral hemodynamics, including cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in patients with cerebrovascular disease. In CADASIL patients with small-vessel disease, ACZ may be possible to increase CBF. We present that reduced CBF was dramatically improved after administration of ACZ on Tc-99m ECD brain perfusion SPECT in a CADASIL patient.     

Assessment of paramedian thalamic infarcts: MR imaging,clinical features and prognosis

Considering the highly variable vascular supply of the thalamic nuclei, MRI and clinical syndromes can be heterogeneous in ischemic diseases. We attempt to determine MRI pattern and to analyse neurological features and prognosis of paramedian infarcts. In a prospective case series within 5 years from 1999 to 2003, MRI, MRA and clinical symptoms of 38 consecutive patients were analysed. The inferomedial (posterior thalamoperforating artery) territory was affected in 89%, and lesions in the anterolateral (tuberothalamic artery) territory occurred in 42%. However, definite attribution to anterolateral or inferomedial territories was not possible in 13%. Neurological manifestations were somnolence (87%), hemisyndromes (79%), cognitive deficits (58%), oculomotor nerve palsies (53%) and vertical gaze palsies (39%). The most common aetiologies were cardiac embolism (42%), intraarterial embolism (16%), small vessel disease (13%) and large artery arteriosclerosis (13%). Pathological MRA findings were encountered in 55%, and in 18%, lesions were only visible on diffusion-weighted imaging. Correlation of MRI pattern and neurological symptoms points out anterolateral thalamic lesions as the cause of amnestic deficits. Intracranial MRA allows a non-invasive prediction of basilar tip occlusion. Our results underline the necessity of additional diffusion-weighted imaging in detecting small thalamic and midbrain lesions.     

Cortical hypometabolism and crossed cerebellar diaschisis suggest subcortically induced disconnection in CADASIL: an 18F-FDG PET study.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in the NOTCH3 gene. As in sporadic small-vessel disease, ischemic lesions are largely confined to subcortical structures, whereas the cortex is spared. CADASIL, therefore, may serve as a model to study subcortically induced remote effects. The purpose of this study was to evaluate with (18)F-FDG PET whether regional cerebral metabolic rate of glucose (rCMRglc) is altered in CADASIL patients and, if so, whether there is evidence of subcortically induced disconnection. METHODS: Eleven CADASIL patients (7 women, 4 men; mean age, 55.8 +/- 6.7 y) without cortical lesions on brain MR images underwent PET after intravenous injection of 120 MBq (18)F-FDG, with calculation of rCMRglc according to a previously published method. For further processing, patient studies were registered to a template of a healthy control group and region-of-interest-based and voxelwise comparisons were performed. RESULTS: In CADASIL patients, mean rCMRglc was significantly reduced in all cortical and subcortical structures, compared with the values in healthy volunteers. In the subcortical gray matter, metabolic rates, given as the percentage of the mean of healthy volunteers, were 49.7%, 65.3%, and 51.6% in the caudate, putamen, and thalamus, respectively. Among cortical structures, the values were 66.9%, 67.9%, 67.2%, and 76.5% for the frontal, parietal, temporal, and occipital lobes, respectively. On an individual level, most patients showed marked asymmetry and inhomogeneities of cortical glucose metabolism. In 6 (55%) CADASIL patients, there was evidence of crossed cerebellar diaschisis. CONCLUSION: This study showed that cortical glucose metabolism is significantly lower in CADASIL patients than in healthy volunteers. The observed decrease in rCMRglc may in part be explained by a reduction of cerebral blood flow and neuronal loss. In addition, our data provide evidence of remote effects secondary to the functional disruption of subcortical fiber tracts in this particular type of small-vessel disease.     

Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison

PURPOSE: To differentiate lesion patterns in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) from those in patients with sporadic subcortical arteriosclerotic encephalopathy (sSAE). MATERIALS AND METHODS: Magnetic resonance (MR; T2-weighted and fluid-attenuated inversion-recovery) images obtained in 28 patients with CADASIL were compared with images obtained in 24 patients with sSAE by using an automated pixel-based group comparison with statistical parametric mapping and regional semiquantitative rating. RESULTS: Visual rating showed higher lesion scores for CADASIL in the temporal and temporopolar white matter (WM). Statistical parametric mapping group analysis independently revealed more extensive bilateral involvement of the anterior temporal and superior frontal WM in CADASIL. There were bilateral signal intensity reductions within the dentate nucleus, deep cerebellar WM, crus cerebri, and thalamus. Lesions extended remarkably more often into arcuate fibers in the temporopolar and paramedian superior frontal lobes in CADASIL. Linear discriminant analysis was used to classify 96% (50 of 52) of the cases correctly, with temporopolar WM and arcuate fiber involvement contributing most to the discrimination function. CONCLUSION: The presented MR imaging criteria are useful in the diagnostic work-up in patients with leukoencephalopathy and help to differentiate CADASIL from sSAE. The observed pattern of vulnerability in CADASIL suggests future directions for research in the pathophysiology of this disorder. In addition, the study demonstrates the potential of automated image analysis to explore MR imaging lesion patterns.