MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited, autosomal dominant condition caused by mutations of the Notch3 gene. Affected individuals have migraine, mood disturbance, and recurrent strokes, often progressing to subcortical dementia and premature death. MRI findings include focal lacunar infarcts and diffuse T2-weighted hyperintensity, or leukoaraiosis. However, such findings are seen much more commonly in patients with cardiovascular risk factors, particularly hypertension, where they are believed to represent cerebral small vessel disease. No previous study has sought to identify specific radiologic markers of CADASIL. METHODS: MRI scans from 20 consecutive patients with CADASIL and 20 patients with sporadic leukoaraiosis due to presumed small-vessel disease were compared using the previously validated semiquantitative MRI rating scale devised by Scheltens et al. Analysis was blinded to clinical category. RESULTS: Scores for hyperintensities of the temporal white matter and external capsule-insula region were significantly higher in patients with CADASIL. Hyperintensity confined to the pole of the temporal lobe was a characteristic finding in CADASIL, occurring in 19 patients with CADASIL but no patients with ischemic leukoaraiosis. Involvement of the external capsule, though less specific, was seen early in the disease course. In a few patients with CADASIL, involvement of the corpus callosum was observed. CONCLUSIONS: Temporal pole hyperintensity is a radiologic marker of CADASIL. Involvement of the external capsule and corpus callosum are also characteristic findings that may help to distinguish the disease.     

Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque‐like lesions

Adult onset leukodystrophy with neuroaxonal spheroids is an uncommon cause of dementia. Both hereditary (autosomal dominant) and sporadic cases have been described. A 41‐year‐old African woman presented with inappropriate behavior and personality change consistent with frontal lobe dysfunction. MRI demonstrated diffuse frontoparietal white matter signal abnormality and volume loss, as well as focal enhancing white matter lesions, while CT scan showed white matter calcifications. She had been gradually deteriorating over the last 5 years, diagnosed as having progressive demyelinating illness. She died of recurrent chest infections. There was no familial history. The brain showed prominent symmetrical white matter changes with greyish discolorization mainly affecting the frontal and parietal lobes, with less involvement of the temporal lobe and only mildly affecting the occipital white matter. Histology revealed deep white matter atrophy with many neuroaxonal spheroids labelled by neurofilament and β‐amyloid precursor protein. In addition, scattered inactive demyelinating plaque‐like lesions were found in the periventricular areas, brainstem and the cervical spinal cord. This case had typical features of an adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque‐like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition.     

CADASIL患者的临床、影像和Notch3基因突变特点及我国研究现状

常染色体显性遗传性脑动脉病伴皮层下梗死和白质脑病（cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL）是一种较为少见的遗传性小动脉病,致病基因为Notch3。我国患者主要表现为皮层下缺血及认知障碍,伴有先兆的偏头痛极少见。影像学特点为多发皮质下梗死灶,侧脑室旁白质多发斑点状异常信号,外囊、前颞区和胼胝体为特征性受累部位。Notch3基因突变热区分布在第11、4和3号外显子,可能存在热点突变。     

CADASIL imitating multiple sclerosis: the importance of MRI markers

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can mimic multiple sclerosis (MS), leading to diagnostic confusion. We report a family with CADASIL in which the index case and the daughter of the index case were initially erroneously diagnosed with MS. Relatively specific magnetic resonance imaging (MPI) markers of CADASIL include involvement of the anterior temporal lobes and external capsules and, as illustrated in this report, these MRI findings may aid in the differentiation of the two conditions.     

Cognitive and neuroimaging profile of a Brazilian family with CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease leading to small infarcts and subcortical vascular dementia. This study presents results from the neuropsychological and neuroimaging evaluation of functionally autonomous individuals of a Brazilian family with CADASIL. The causal mutation was confirmed in four family members. Seven individuals from two generations were evaluated using the CERAD battery and additional neuropsychological tests and were submitted (6 individuals) to magnetic resonance imaging (MRI) of the brain with specific protocols for white matter lesion quantification. Apraxic changes and fast progression over nine months (neuropsychological reevaluation of 6 individuals) were found in many individuals. The MRI study suggests greater involvement of frontal lobes in more severely affected individuals. Even functionally independent individuals may exhibit significant neuropsychological and neuroimaging changes. Apraxia, little commented on in literature, and rapidly progressive cognitive changes were found in this group.     

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL): a case report with review of literature

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is an inherited arterial disease, commonly overlooked or misdiagnosed. We report a case of CADASIL in a 51 years old woman who presented with progressive subcortical dementia, recurrent ischemic events and seizures in the absence of known vascular risk factors of five years' duration. Her mother had a history of similar illness. Magnetic resonance imaging (MRI) of brain revealed subcortical and deep white matter hyperintense lesions within the cerebral white matter on T2-weighted images. DNA mutation of Notch 3 gene confirmed the diagnosis of CADASIL.     

Frontal and temporal volume size of grey and white matter in patients with schizophrenia

We previously performed a magnetic resonance imaging (MRI) parcellation study that showed smaller grey and white matter volumes of the temporal lobes and increased CSF volumes in the frontal and temporal lobe in men with schizophrenia. One question that arose from this earlier study was whether similar structural changes in the brain are found in a large group of schizophrenic patients consisting of both men and women. In the present study, MRI scans were acquired from 94 patients of both genders with schizophrenia and 101 healthy subjects. After the automatic segmentation of grey matter, white matter, and cerebrospinal fluid, the frontal, temporal, parietal, and occipital lobes were automatically parcellated according to the Talairach atlas. Compared with healthy subjects, schizophrenic patients showed significantly smaller volumes of grey matter in the temporal lobe and white matter in the frontal lobe. Schizophrenic patients had a greater CSF volume in the frontal and temporal lobes. These results suggest that volume reduction in the cerebrum is prominent in the frontal and temporal lobes in both men and women with schizophrenia.     

White matter microstructure alterations in bipolar disorder

Genetic, neuropathological and magnetic resonance imaging findings support the presence of diffuse white matter cytoarchitectural disruption in bipolar disorder. In this study, diffusion-weighted imaging (DWI) was applied to study cortical white matter microstructure organisation in 24 patients with DSM-IV bipolar disorder and 35 matched normal controls. DWI images were obtained using a 1.5 Tesla scanner and apparent diffusion coefficient (ADC) values were determined over regions of interest placed, bilaterally, in the frontal, temporal, parietal, and occipital white matter. Significantly increased ADC values were found in bipolar patients with respect to normal controls in the right temporal lobe, left parietal lobe and bilateral occipital lobes. ADC values did not associate significantly with age or with clinical variables (p>0.05). Diffuse cortical white matter alterations on DWI in bipolar disorder denote widespread disruption of white matter integrity and may be due to altered myelination and/or axonal integrity.     

Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

To test the hypothesis that an apoptotic process plays a role in the pathogenesis of cerebral lesions in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), we examined samples from frontal, temporal, insular, and occipital regions, basal ganglia, and cerebellum from 4 patients with CADASIL, 2 with Binswanger disease, and 3 controls. Apoptotic cells were identified using in situ end labeling and activated caspase 3 immunostaining. Immunolabeling for Notch3, the beta-amyloid protein precursor, and phosphorylated neurofilament protein was performed on successive sections. Apoptosis of vascular cells was markedly increased in status cribrosus in CADASIL, both in basal ganglia and subcortical white matter, suggesting that concomitantly with Notch3 deposition it may play a causative role in the dilatation of Virchow-Robin spaces. Neuronal apoptosis was found in CADASIL, mostly in cortical layers 3 and 5. Its severity correlated semiquantitatively with the extent of ischemic lesions and axonal damage in the underlying white matter. It was more severe in demented patients. Only occasional apoptotic neurons were found in the Binswanger cases and none in the controls. This supports the view that neuronal apoptosis may contribute to cortical atrophy and cognitive impairment in patients with CADASIL and that it may, at least partly, result from axonal damage in the underlying white matter.     

Neuropsychiatric manifestations in CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-artery disease of mid-adulthood caused by mutations of the NOTCH3 gene. The disease is responsible for widespread white-matter lesions associated with lacunar infarctions in various subcortical areas. The disease is responsible for migraine with aura and ischemic strokes, and is associated with various degrees of cognitive impairment and with mood disturbances. CADASIL is considered as a unique model to investigate what is known as "subcortical ischemic vascular dementia." Recent data suggest that the number of lacunar infarctions and severity of cerebral atrophy are the main magnetic resonance imaging markers associated with cognitive and motor disabilities in this disorder. Mood disturbances are reported in 10% to 20% of patients, most often in association with cognitive alterations. Their exact origin remains unknown; the presence of ischemic lesions within the basal ganglia or the frontal white matter may promote the occurrence of these symptoms. Further studies are needed to better understand the relationships between cerebral lesions and both cognitive and psychiatric symptoms in this small-vessel disease of the brain.     

Incipient CADASIL

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.     

Report of a patient with CADASIL having a novel missense mutation of the Notch 3 gene--association with alopecia and lumbar herniated disk]

We report a 52-year-old man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting dementia, alopecia and lumbar herniated disk. He had an episode of stroke and migraine-like headache lasting for 5 minutes. A lot of members had cerebral infarction in this family. Brain magnetic resonance imaging demonstrated, on T2-weighted images, numerous hyperintense lesions suggestive of small infarcts in the basal ganglia and diffuse hyperintense lesions in the cerebral white matter. The clinical symptoms, the family history and the MRI findings suggested the diagnosis of CADASIL. However, the patient also showed alopecia and lumbar herniated disk, both are characteristic features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). The DNA analysis of the Notch 3 gene identified a novel missense mutation Cys174Phe in this patient. Our case report indicated the importance of the DNA analysis for the diagnosis of CADASIL.     

可复性后部脑病综合征的影像学诊断

目的探讨可复性后部脑病综合征（PRES）的影像学表现.方法回顾性分析了12例PRES病人的临床和影像学资料,其中9例为子痫/先兆子痫,2例为高血压脑病,1例为环孢菌素A（CSA）的神经毒性.12例均行MRI检查,其中7例同时行钆喷替酸葡甲胺（Gd-DTPA）增强扫描,4例行磁共振血管造影（3D-TOF MRA）检查,1例行弥散加权成像（DWI）.7例行CT平扫检查,2例行脑血管造影（DSA）检查.结果MRI显示病灶基本上呈双侧对称性分布,多数病灶位于顶、枕叶脑实质内,T1WI呈等或略低信号,T2WI呈高信号,FLAIR像显示皮层和皮层下白质明显高信号影,较T1WI、T2WI更加清楚.注射Gd-DTPA后多无明显异常对比增强.1例DWI显示双侧顶、枕叶及额叶皮层内弥散受限呈高信号,ADC图显示邻近的皮层下白质呈高信号.4例CT显示双侧顶、枕叶及额叶对称性斑片状低密度影,3例CT未见异常.经对症处理后复查示所有病灶几乎完全吸收消失.结论PRES的影像学表现具有特征性.MRI应作为诊断本病的首选手段.     

Acute vestibular syndrome in a patient with cerebral autosomal dominant leukoencephalopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of small vessel disease in which the pons may show lacunar infarcts and leukoaraiosis. Acute pure vestibular syndrome may be due to caudal pontine lesions and is probably underestimated. We describe a case of CADASIL with acute vestibular syndrome mimicking peripheral vestibulopathy, and evidence of focal infarction in the ponto-medullary junction at gadolinium-enhanced MRI including diffusion-weighted imaging, involving the area of the right vestibular nucleus and root entry zone of the ipsilateral vestibular nerve bundle. In CADASIL, both focal brainstem lesions and leukoaraiosis may parallel supratentorial white matter changes and may be related to poor outcome. Their actual extent should be evaluated in longitudinal studies that might predict clinical outcome and progression of disability.     

Regional distribution of white matter hyperintensities in vascular dementia, Alzheimer's disease and healthy aging

BACKGROUND: White matter hyperintensities (WMH) on MRI scans indicate lesions of the subcortical fiber system. The regional distribution of WMH may be related to their pathophysiology and clinical effect in vascular dementia (VaD), Alzheimer's disease (AD) and healthy aging. METHODS: Regional WMH volumes were measured in MRI scans of 20 VaD patients, 25 AD patients and 22 healthy elderly subjects using FLAIR sequences and surface reconstructions from a three-dimensional MRI sequence. RESULTS: The intraclass correlation coefficient for interrater reliability of WMH volume measurements ranged between 0.99 in the frontal and 0.72 in the occipital lobe. For each cerebral lobe, the WMH index, i.e. WMH volume divided by lobar volume, was highest in VaD and lowest in healthy controls. Within each group, the WMH index was higher in frontal and parietal lobes than in occipital and temporal lobes. Total WMH index and WMH indices in the frontal lobe correlated significantly with the MMSE score in VaD. Category fluency correlated with the frontal lobe WMH index in AD, while drawing performance correlated with parietal and temporal lobe WMH indices in VaD. CONCLUSIONS: A similar regional distribution of WMH between the three groups suggests a common (vascular) pathogenic factor leading to WMH in patients and controls. Our findings underscore the potential of regional WMH volumetry to determine correlations between subcortical pathology and cognitive impairment.     

Dilation of Virchow-Robin spaces in CADASIL

To precise the severity of dilated Virchow-Robin spaces (VRS) in CADASIL patients and to determine their correlation with clinical presentation and other abnormalities on cerebral Magnetic Resonance Imaging (MRI). Dilated VRS were previously associated with aging, hypertension, dementia, epilepsy or migraine. We already reported increased frequency of enlarged VRS in CADASIL patients when compared with family members without the affected haplotype. We analysed clinical and MRI data from 50 CADASIL patients collected prospectively in our center. The presence of dilated VRS was assessed in the subcortical white matter of temporal lobes, the centrum semi-ovale and the basal ganglia. Their severity in each region was evaluated according to the scale proposed by Heier. We compared the clinical data, the severity of white matter abnormalities and the presence of microbleeds in patients with and without dilated VRS. Seventy-eight percent of patients in our series had dilated VRS, mostly located in the lentiform nuclei (94%) and subcortical white matter of the temporal lobes (66%). The severity of these lesions was variable but not correlated neither to the extent of white matter abnormalities nor to the clinical presentation in our patients. Only the age was found to be related to the extent of dilated VRS. Dilated VRS are frequent in CADASIL and mostly located in the temporal white matter and basal ganglia. The dilation of perivascular spaces does not seem to be directly related to the occurrence of ischemic or hemorrhagic lesions in CADASIL. In contrast, the relation with age suggests that either aging, progression of vascular wall alterations during the course of the disease, or both of these processes can favour the extension of VRS in CADASIL.     

CADASIL: a monogenic condition causing stroke and subcortical vascular dementia

Mutations in Notch3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited small vessel disease leading to subcortical strokes and vascular dementia. The phenotypic presentation is variable but remarkable for a high frequency of migraine with aura. Magnetic resonance images show a microangiopathic pattern of lesions. Prominent involvement of the temporopolar white matter and involvement of the temporopolar arcuate fibers are conspicuous findings seen in many patients. The underlying angiopathy is characterized by a unique type of ultrastructural basal lamina deposits and by degeneration of vascular smooth muscle cells which are the major source of Notch3 expression. In line with these findings there is evidence for a functional impairment of vascular smooth muscle cells. CADASIL has opened a new perspective in studying basic mechanisms of vessel wall degeneration and ischemic tissue damage related to small vessel disease.     

Memory and executive function in older adults: relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities

Forty-eight healthy adults aged 65-85 were recruited for structural magnetic resonance scans after an extensive neuropsychological battery that ensured a high degree of variability across the sample in performance on long-term memory tests, and on tests traditionally thought to rely on prefrontal cortex. Gray matter volumes were measured for three gyri in the frontal lobe (superior, middle, inferior), six gyri in the temporal lobe (superior, middle, inferior, fusiform, parahippocampal, and hippocampus), and the occipital lobe. Gray matter volumes declined across the age range evaluated, but with substantial regional variation--greatest in the inferior frontal, superior temporal, and middle temporal gyri but negligible in the occipital lobe. Both memory performance and executive function declined as the number of hyperintense regions in the subcortical white matter increased. Memory performance was also significantly correlated with gray matter volumes of the middle frontal gyrus (MFG), and several regions of temporal neocortex. However, the correlations were all in the negative direction; better memory performance was associated with smaller volumes. Several previous reports of significant negative correlations between gray matter volumes and memory performance are described, so that the possible reasons for this surprising finding are discussed.     

热射病导致的脑梗死或脑出血的诊治分析

目的 探讨热射病导致的脑梗死或脑出血的影像学表现、治疗方法及其效果。方法 回顾性分析2012～2022年收治的20例热射病导致的脑出血或脑梗死的临床资料。结果 2例出现微出血病灶,部位为右额叶及左顶叶;18例出现缺血样改变,包括放射冠、基底节、额叶、颞叶、顶叶、枕叶、皮层下白质、胼胝体、海马,其中2例伴有明显脑水肿。出院时,11例恢复正常,未遗留明显肢体活动障碍、言语障碍及逻辑思维能力障碍;2例出现认知功能减退,主要存在语言表达能力障碍、遵嘱动作较差、小脑共济失调（轮替试验阳性、Romberg阳性）;3例深度昏迷,GCS评分3～4分;4例死亡。结论 热射病导致的脑梗死或脑出血,临床少见,多数病人保守治疗预后良好。建议早期进行康复治疗,以减少神经功能障碍。     

Megalencephalic leukoencephalopathy: a further case of a new neurodegenerative white matter disease

The case is presented of a 4.5-year-old boy with cystic megalencephalic leukoencephalopathy who met the diagnostic criteria of a recently described neurodegenerative white matter disorder, i.e. leukoencephalopathy with swelling and a discrepancy mild clinical course (van der Knaap 1995). He demonstrated an extremely mild and slowly progressive clinical course with near normal psychomotor development, particularly of mental functions, which contrasted with somewhat disturbed gross and fine motor skills. Repeated CT and MRI scanning showed extensive hemispheral cerebral white matter changes and demonstrated predominant frontal involvement of the periventricular and subcortical white matter. MRI was more sensitive in the detection of preserved structures, i.e. occipital subcortical and central white matter, as well as in the visualization of swelling and cystic lesions in the tip of the temporal lobes, which represent the hallmark of this entity. Thus, MRI is an essential diagnostic tool for this entity.