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.     

伴皮质下梗死和白质脑病常染色体显性遗传性脑动脉病CT平扫特点

目的：探讨伴皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）CT平扫特点。方法：对8例经临床、MRI、病理学及基因检查确诊为CADASIL患者的CT平扫资料进行回顾性分析。结果：CADASIL患者脑CT平扫特点主要表现为颞极、额叶前部白质疏松,可伴有腔隙性梗死灶,随年龄增长上述病灶逐渐加重。结论：CADASIL病例CT平扫存在特征性的脑白质病变,CT对该病的筛选有重要作用。     

Frequency of subclinical lacunar infarcts in ischemic leukoaraiosis and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

BACKGROUND AND PURPOSE: Small vessel cerebrovascular disease is an important cause of vascular cognitive impairment. It is usually sporadic but also occurs secondary to the genetic disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Recurrent lacunar stroke is a characteristic feature, although symptomatic events are relatively rare, making large numbers necessary for evaluation of potential therapies. Diffusion-weighted imaging is sensitive to acute ischemic lesions and differentiates them from chronic infarcts. Detection of asymptomatic lacunar infarcts with diffusion-weighted imaging is a potential surrogate marker for treatment trials. In this study, the frequency of asymptomatic new lesions in ischemic leukoaraiosis and CADASIL was determined as a step toward assessing the potential of this technique as a surrogate marker of disease activity. METHODS: Fifty patients with sporadic small vessel disease and 19 patients with CADASIL underwent diffusion-weighted imaging. All had been asymptomatic for 3 months before imaging. Diffusion-weighted images were screened by two raters for new lesions; lesions were confirmed as recent by a visible reduction of diffusivity on the corresponding apparent diffusion coefficient maps. RESULTS: Recent ischemic lesions were identified in four patients with sporadic small vessel disease (8.0%) and two patients with CADASIL (10.5%). CONCLUSION: Asymptomatic new lesions are found in cases of sporadic small vessel disease and CADASIL. The frequency of new lesions suggests that this approach has a potential role as a surrogate marker in therapeutic trials that warrants further investigation.     

常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病患者的MR定量指标及其与临床的关系

目的 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)患者的白质高信号和脑体积进行定量分析,并探讨其与临床的关系.方法 15例通过病理检查确诊为CADASIL的患者进行常规MR扫描,统计脑半卵圆中心、内囊后肢、外囊、胼胝体和颞极白质受病变累及情况.利用计算机后处理软件计算标准化颅脑体积和白质高信号占颅脑体积的百分比,并与年龄、美国国立卫生研究院卒中量表(NIHSS)和简易精神状态检查(MMSE)量表评分进行Spearman相关性分析.结果 CADASIL患者的白质病变累及部位依次为:半卵圆中心(13/15)、颞极白质(10/15)、外囊(8/15)、内囊后肢(5/15)、胼胝体(4/15).白质高信号占颅脑体积的百分比为(5.7±1.4)%,标准化颅脑体积为(1602±58)×103mm3.年龄与标准化颅脑体积呈负相关(r=-0.555,P＜0.05);白质高信号百分比与NIHSS、MMSE量表评分分别呈正、负相关(r=0.522,P＜0.05;r=-0.679,P＜0.01);标准化颅脑体积与NIHSS评分呈负相关(r=-0.624,P＜0.05).结论 CADASIL患者的白质高信号和脑体积可以定量测量,这两种影像学指标可以在一定程度上反映患者的病情.白质高信号的发展可能预示患者认知功能的下降.     

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.     

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.     

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathic syndrome related to a genetic defect on chromosome 19. Characteristic changes in CADASIL can be observed onT2-weighted MR images in the subcortical white matter. The purpose of this study was to measure changes of regional cerebral blood volume (rCBV) with dynamic contrast-enhanced MR imaging and to correlate the changes to disability and cognitive performance. METHODS: We obtained rCBV measurements of 24 individuals with proven CADASIL on a 1.5-T MR imaging unit. A susceptibility-weighted MR imaging sequence was used for bolus tracking. Principles of the indicator dilution theory were applied to estimate values of absolute rCBV (mL/100 g). Disability was determined by using the Rankin scale, and overall cognitive performance was assessed by using the Mini-Mental State Examination. RESULTS: The mean rCBV in the subcortical white matter that was hyperintense on the T2-weighted images (2.7 +/- 0.8 mL/100 g) was significantly lower than the rCBV in the white matter that appeared normal on the T2-weighted images (4.4 +/- 1.3 mL/100 g) (P <.05). The mean rCBV in the gray matter was within the normal range (8.3 +/- 1.7 mL/100 g). Both cognitive impairment and disability negatively correlated with rCBV in the subcortical white matter that was hyperintense (P <.05) but not with rCBV in the normal appearing white matter. rCBV did not correlate with age. CONCLUSION: rCBV measured in the hyperintense subcortical white matter in individuals with CADASIL was decreased and inversely correlated with disability and cognitive impairment.     

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.     

Role of subvoxel free fluid on diffusion parameters in brain tissue with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and its correlation with physical disability: histogram analysis of standard and fluid-attenuated MR diffusion

BACKGROUND AND PURPOSE: Subcortical signal intensity abnormalities and lacunar infarcts are the radiologic hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. MR diffusion studies reveal abnormalities in lesions and also within normal appearing white matter. To further characterize the underlying pathologic abnormality, we evaluated the role of subvoxel free fluid in brain with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy on diffusion parameters and physical disability and analyzed the interrelation between diffusion variables and nonlacunar T2 lesion load. METHODS: Mean diffusivity maps from fluid-attenuated and standard diffusion images of 13 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and seven age-matched control participants were compared by means of histogram analysis for three tissue compartments (whole brain parenchyma, normal appearing brain tissue, and nonlacunar lesions) by using a semiautomated region growing algorithm to define whole brain parenchyma and lesions on fluid-attenuated images. RESULTS: In both patients and control participants, the average mean diffusivity of whole brain parenchyma was lower on fluid-attenuated than on standard images (P <.001). Average mean diffusivity and peak location for all compartments were significantly elevated in patients (P <.001) and higher for lesions than for normal appearing brain tissue on both types of images (P <.001). The difference between standard and fluid-attenuated average mean diffusivity of normal appearing brain tissue, reflecting the subvoxel free fluid content, was elevated in patients (P <.05) and correlated closely with the Rankin score (Spearman's rank correlation coefficient = 0.889, P <.001). Average mean diffusivity of whole brain parenchyma and normal appearing brain tissue correlated strongly with the nonlacunar T2 lesion load (Pearson's correlation coefficient = 0.743-0.928, P <.005). CONCLUSION: This study shows that standard diffusion measurements are contaminated by free fluid partial volume effects for patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and for control participants. It also provides evidence of a clinical significance of increased subvoxel free fluid in normal appearing brain with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which may be more important than either global atrophy, increased diffusivity or, T2 lesion load.     

Reversible posterior leukoencephalopathy syndrome: evaluation with diffusion-tensor MR imaging

PURPOSE: To characterize the changes in brain water diffusion caused by reversible posterior leukoencephalopathy syndrome (RPLS). MATERIALS AND METHODS: Twelve patients with the clinical features and conventional magnetic resonance (MR) imaging findings of RPLS underwent diffusion-tensor echo-planar MR imaging. The isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) were measured in posterior regions of diffusion abnormality and in anterior areas of normal-appearing brain. RESULTS: Across all 12 subjects, the mean D of (1.09 +/- 0.13 [SD]) x 10(-3) mm(2)/sec in affected posterior regions was 26% greater than its value of (0.87 +/- 0.07) x 10(-3) mm(2)/sec in normal-appearing anterior regions. The mean A(sigma) of 0.15 +/- 0.03 in posterior regions was 35% less than its value of 0.23 +/- 0.02 in anterior regions (t(11) = 9.58; P <.001). There was a significant inverse correlation between D and A(sigma) in posterior regions (r = -0.67; P <.018) but not in anterior regions (r = -0.12; P =.719). A follow-up study performed in one patient after resolution of symptoms documented reversal of elevated isotropic diffusion and at least partial recovery of anisotropy loss. CONCLUSION: The increased magnitude of brain water diffusion characteristic of RPLS is accompanied by reduced A(sigma). The magnitudes of these two effects are correlated and may be reversible. These observations support the proposal that vasogenic edema due to cerebrovascular autoregulatory dysfunction is the underlying pathophysiologic mechanism in uncomplicated RPLS.     

Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA

To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction.     

Occlusive and reperfused myocardial infarcts: differentiation with Mn- DPDP--enhanced MR imaging

To assess whether the administration of manganese N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid (DPDP) permits differentiation between occlusive and reperfused infarcts, the authors subjected rats to either 6 hours of left coronary artery occlusion (n = 13) or 2 hours of occlusion followed by 4 hours of reperfusion (n = 10) before magnetic resonance (MR) imaging. Electrocardiographic-gated T1-weighted images were obtained before and for 1 hour after injection of 400 mumol/kg of Mn-DPDP. On T1-weighted images obtained before injection of Mn-DPDP. no significant differences in signal intensity were observed between normal and infarcted regions. Use of Mn-DPDP permitted delineation of the area of infarction. The pattern of enhancement in the injured zone was different for occlusive and reperfused myocardial infarcts. In rats with occlusive infarcts, In rats with occlusive infarcts, three well-defined zones were seen. Epicardium and endocardium were enhanced, while the midmyocardial zone was hypointense. The midmyocardial signal intensity gradually increased during the 60 minutes after injection. In rats with reperfused infarcts, the injured area was uniformly and intensely enhanced. Histologic examination confirmed the presence and location of myocardial infarct. Mn-DPDP may improve the detection and delineation of acute myocardial infarcts, demonstrate perfusion of the infarct, and permit discrimination between reperfused and occlusive infarcts.     

Cerebral ischemia: evaluation with contrast-enhanced MR imaging

Eighty patients with a total of 82 ischemic lesions were examined with contrast-enhanced MR imaging 1 hr to 1 month after onset of symptoms. The studies were reviewed retrospectively to determine the presence of arterial enhancement and the patterns of parenchymal enhancement. Arterial enhancement was often detected on the initial MR examination (45%), was frequently demonstrated in cortical infarction (86%), in some cases preceded the development of signal changes on T2-weighted images, and resolved by 11 days. The presence of arterial enhancement appeared to be a better indicator of clinical severity than was the presence of proximal vessel occlusion on MR or angiographic studies. Two patterns of parenchymal enhancement were seen: progressive enhancement and early and/or intense enhancement. In patients with the progressive pattern, parenchymal enhancement on postcontrast T1-weighted images was rarely seen before 7 days, while signal abnormalities on T2-weighted images were intense during the first few days. The early and/or intense enhancement pattern was usually present within the first 3 days, approximated or exceeded the area and intensity of signal changes on T2-weighted images, and was usually associated with minimal or reversible neurologic sequelae (except when located in or near a watershed zone), suggesting a lesser degree of ischemic insult than was associated with the progressive pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI

A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myo-inositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC.     

MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms

BACKGROUND AND PURPOSE: Three families with adult-onset autosomal dominant leukodystrophy (ADLD) presenting autonomic dysfunction as the first symptom are reported. We describe detailed MR appearances of the brain in 2 new families and neuropathology in 2 patients and compare the findings with those in other adult-onset leukodystrophies. METHODS: Twenty subjects (12 women and 8 men; age range, 29-70 years) from 2 unrelated families with ADLD were examined with MR. Six subjects were asymptomatic. Fourteen had autonomic dysfunction. Eleven of them also had pyramidal signs and ataxia. The brains of 2 autopsied patients were examined histopathologically. RESULTS: Two subjects manifested no neurologic symptoms, signs, or MR pathology. Eighteen subjects displayed radiologic abnormalities ranging from subtle T2 high-signal-intensity changes in the upper corticospinal tract to extensive confluent white matter changes, predominantly in a frontoparietal distribution, along the corticospinal tracts down to the medulla oblongata and in the upper and middle cerebellar peduncles. Periventricular white matter was spared or less affected than the adjacent white matter. Histopathology revealed marked loss of cerebral and cerebellar myelin without signs of inflammation. Oligodendrocytes were relatively spared, the number of axons not markedly decreased, and reactive gliosis was modest. The number of Purkinje cells in the cerebellum was reduced. CONCLUSIONS: Two families with adult-onset ADLD with the disease entity originally reported by Eldridge et al. (N Engl J Med 1984;311:948-53) were described. We propose naming the disease "adult-onset ADLD with autonomic symptoms." The characteristic radiologic findings, combined with the clinical symptoms and mode of inheritance, enable the diagnosis.     

Perinephric hemorrhage in autosomal dominant polycystic kidney disease: CT and MR findings

Perinephric hemorrhage is a rare complication of autosomal dominant polycystic kidney disease (ADPKD). Of 66 patients in our series, it occurred in two (3%) and their clinical and radiologic findings are described. Computed tomography accurately delineated both hematomas and revealed an underlying ruptured hemorrhagic renal cyst in one patient. Computed tomography did not show the cause of hemorrhage in the other patient, but magnetic resonance (MR) imaging detected an underlying hemorrhagic cyst. Perinephric hemorrhage in ADPKD probably results from rupture of hemorrhagic renal cysts into the perinephric space. Computed tomography is the optimal method for its evaluation. However, MR may supplement CT findings since it detects more hemorrhagic cysts than CT and helps distinguish them from carcinomas. Perinephric hemorrhage in ADPKD can usually be managed conservatively.     

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.