1,2-二氯乙烷中毒性脑病19例临床特点分析

目的探讨1,2-二氯乙烷(1,2-DCE)中毒性脑病的临床及影像学特征。方法回顾性分析2009年7月~2015年7月收治的19例1,2-DCE中毒性脑病病例,对其临床特点及影像学资料进行总结分析。结果所有患者均有职业暴漏史,其主要表现为头痛、头晕、恶心、睡眠障碍,乏力、记忆下降、意识障碍、癫痫发作等症状。头颅MRI检查示在皮质下白质、双侧苍白球和小脑齿状核广泛的脑水肿,双侧大脑白质内对称性大片状异常信号影,T_1WI呈低信号,T_2WI高信号,DWI序列上见病灶呈高异常信号,脑水肿、脑肿胀明显。结论根据典型的临床和神经影像学特点,结合职业接触含有l,2-DCE的物质,可诊断1,2-DCE中毒性脑病。     

吸食海洛因致海绵状白质脑病的CT及MRI诊断

目的评价海洛因中毒所致的海绵状白质脑病的CT、MRI表现及诊断价值.方法搜集6例海洛因海绵状白质脑病的CT及MRI资料,全部患者均进行MRI检查,检查序列包括T1WI、T2WI、FLAIR序列,其中2例同时行颅脑CT扫描. 结果全部患者MRI显示对称性双侧小脑半球、大脑半球后部、内囊后肢、胼胝体压部、脑干等皮质下白质为主的多发性大片状长T1、长T2信号,加强后病灶无强化;2例行头颅CT检查显示两大脑半球皮质下白质、基底节及两侧小脑呈对称性广泛低密度灶,无占位效应.结论海洛因中毒所致的海绵状白质脑病具有特征性的MRI表现,MRI对本病的诊断具有重要价值.     

颅脑弥漫性轴索损伤的MRI诊断

目的探讨颅脑弥漫性轴索损伤的磁共振影像特点。方法对11例经临床证实的颅脑弥漫性轴索损伤的磁共振检查资料进行回顾性分析。结果颅脑弥漫性轴索损伤的磁共振影像表现:(1)11例T1WI序列均显示脑沟变浅,脑回粗大,脑室变窄;(2)全部病例双侧大脑半球皮质下区及胼胝体上显示斑点状、小片状异常信号,呈等或短T1、短T2信号,周围显示水肿带,边缘模糊;(3)扩散加权成像序列上双侧大脑半球皮质下区及胼胝体上显示更多的斑点状低信号周围显示水肿带;(4)7例显示小脑幕下疝。结论磁共振成像对颅脑弥漫性轴索损伤诊断准确可靠,临床价值极高。     

可逆性后部白质脑病综合征8例临床分析

目的 探讨可逆性后部白质脑病综合征(RPLS)临床和影像学特点. 方法回顾性分析8例RPLS患者临床及影像学资料.结果 本组患者继发于高血压2例,子痫2例,产褥期子痫1例,血栓性血小板减少性紫癜1例,肺性脑病1例,颅咽管瘤1例.临床表现:6例出现头晕,4例出现癫NFDCC发作,3例出现头痛, 2例出现视物模糊,恶心、呕吐、精神异常、脑疝、左侧轻偏瘫各1例.6例无神经系统定位体征.影像学检查颅脑CT检查 1例脑干低密度影,4例出现枕叶低密度影(其中2例广泛脑白质水肿),1例未发现异常.7例颅脑MRI检查(T1、T2、FLAIR),6例均有枕叶受累,3例同时累及额颞叶,1例累及脑干和小脑,1例累及尾状核头和丘脑,在脑叶呈脑回样,在其他部位呈斑片样异常信号;T1WI呈略低或等信号,T2WI呈高信号,FLAIR像显示皮质和皮质下白质明显高信号.结论 头晕、头痛、视觉障碍和癫NFDCC发作是RPLS主要临床表现,影像学特征主要为大脑后部白质对称性长T1 、长T2 信号.     

可逆性后部白质脑病综合征临床及影像学特点分析

目的 探讨可逆性后部白质脑病综合征(RPLS)的临床和影像学特点.方法 回顾性分析9例RPLS患者的临床及影像学资料.结果 9例患者临床表现以头痛、意识障碍、癫发作、视觉异常为主;头颅MRI检查有大脑半球后部白质为主的T1WI低信号,T2WI、Fair像呈高信号的病灶,且大多双侧对称.结论 头痛、意识及精神障碍、癫发作、视觉异常、是可逆性后部白质脑病综合征主要临床表现,影像学特征主要为大脑后部对称性、可逆性脑白质损害.     

表皮样囊肿非典型MRI表现

目的探讨非典型表皮样囊肿MRI表现。方法回顾性分析4例经手术病理证实的表皮样囊肿的MRI资料。结果例1肿瘤位于左前中颅凹底,信号不均,T1WI呈高及低信号,T2WI及FLAIR像均呈高信号,其内有细曲线样等信号,左侧大脑半球脑裂、脑沟内散在点条状高信号。例2肿瘤位于左颞极,T1WI、T2WI及FLAIR像均为高信号,脑室、脑裂、脑池及部分脑沟内见点状高信号,脂肪抑制像信号减低。例3肿瘤位于右中颅凹底,边界清晰,呈类圆形,信号不均,T1WI呈低信号,其内见弧条状高信号,T2WI为高信号,其内见弧条状低信号,FLAIR像信号稍低,其内见云絮状稍高信号。例4肿瘤位于脑干前方,边界清晰,形态欠规则,T1WI、T2WI及FLAIR像均为高信号,脂肪抑制像仍为高信号。结论表皮样囊肿可表现出多种不典型MRI征象,信号特点多样,且可破裂播散至脑室内形成脂-液平面及在蛛网膜下腔内见到点条状脂肪信号,硬膜外表皮样囊肿更不具特异性,认识这些征象对临床诊断及治疗都有重要意义。     

1,2-二氯乙烷中毒性脑病6例临床分析

目的探讨1,2二氯乙烷中毒性脑病的临床表现及影像学分析。方法对6例1,2二氯乙烷中毒性脑病患者的临床、头部MRI、治疗预后进行观察分析。结果该组6例为亚急性或迟发性起病,病情进行性加重,均有明确的1,2二氯乙烷接触史。亚急性起病以颅高压及全脑症状为主,迟发性以精神状态改变及锥体外系症状为主。头部MRI表现为对称、弥漫、累及灰白质的病变,主要累及大脑半球、小脑齿状核、基底节、丘脑等。经治疗后,6例中2例因脑疝死亡,3例临床症状改善不明显,1例临床治愈。结论认识1,2二氯乙烷中毒性脑病各阶段的临床表现及影像学特点,使本病患者得到及时有效诊治。有1,2二氯乙烷接触史患者需定期复查MRI,尽早发现病变,降低遗留神经系统损害的几率及程度。     

偏头痛与脑白质变性

目的探讨偏头痛与脑白质变性的关系及其可能形成机制。方法偏头痛患者(n=55)行头颅MRI检查,部分行脑ECT脑血流灌注显像。同期本院非神经系统疾病并行头颅MRI检查的内科住院病人作为对照组(n=51)。结果偏头痛组中,头颅MRI显示16例脑白质内见小点片样等T1或稍长T1,长T2异常信号,以多发性为主;对照组仅3例患者可见大脑半球白质内异常信号,两者之间差异有显著性意义。偏头痛组中3例患者做头颅ECT脑血流灌注显像检查,在单侧或双侧的额、颞部的脑局部血流灌注下降。对照组中4例行头颅ECT,未见脑局部血流灌注下降。结论反复偏头痛发作可能同脑白质变性具有相关性,其形成机制可能与脑血管舒缩功能异常等有关。     

MELAS型线粒体脑肌病的MRI诊断价值

目的探讨MRI对MELAS型线粒体脑肌病的诊断价值。方法6例经临床诊断的MELAS型线粒体脑肌病行T1WI、T2WI、FLAIR、DWI检查。结果MRI显示病变范围广泛,多位于单侧或双侧的顶、枕、颞叶脑回皮质、皮质下白质的多发缺血样病灶,不按动脉供血区分布,还可见与年龄不相符的脑萎缩。结论MRI能显示MELAS型线粒体脑肌病的脑内病变部位、形态和范围,对临床诊断和治疗有重要价值。     

儿童局灶性皮质发育不良的磁共振高分辨成像特征

目的探讨儿童局灶性皮质发育不良(Focal cortical dysplasia,FCD)的3D高分辨核磁共振(MRI特征。方法回顾性分析2015年4月-2018年6月山东大学齐鲁儿童医院收治的42例经病理证实为FCD的患儿MRI资料,观察下述征象:局灶性灰白质分界模糊、皮质结构异常(增厚或变薄)、T2WI/FLAIR白质信号增高,伴或不伴transmantle征(皮层下白质内向脑室方向延伸的异常信号),T2WI/FLAIR灰质信号增高,异常脑沟或脑回形态及节段性和/或脑叶发育不全/萎缩。结果 42例患儿中,37例(88.1%)可见MRI阳性征象,FCDⅠ型13例(35.1%),主要MRI特征为局灶性灰白质分界模糊、相应部位皮质结构异常及T2WI/FLAIR白质信号增高;FCDⅡ型17例(45.9%),表现为局灶性灰白质分界模糊及皮质结构异常、T2WI/FLAIR白质信号增高及transmantle征;FCDⅢ型共7例(18.9%),其中海马萎缩2例(28.6%)、胚胎发育不良性神经上皮瘤(Dysembryoplastic neuroepithelial tumor,DNET) 2例(28.6%)、节细胞瘤1例(14.3%)、软化灶并胶质增生2例(28.6%)。结论 FCD患儿的3D高分辨MRI特征具有特异性,可提高FCD病灶检出率。     

Diagnosis and prognosis evaluation of 1,2-dichloroethane encephalopathy--magnetic resonance imaging combined with diffusion tensor imaging and magnetic resonance spectroscopy study

Neuroimaging findings in 1,2-dichloroethane (1,2-DCE) encephalopathy have seldom been reported. We present the comprehensive neuroimaging findings, conventional magnetic resonance imaging (MRI) combined with diffusion tensor imaging (DTI) and 1 H-magnetic resonance spectroscopy ( 1 H-MRS), in a case of 1,2-DCE encephalopathy. On day-4 the signal intensity of the lesions on diffusion-weighted imaging (DWI) was higher than that with T2-weighted imaging (T2WI); mean apparent diffusion coefficient (ADC) values for lesions were lower than control values. On day-20, the mean ADC value was increased gradually, whereas the mean fractional anisotropy (FA) of the lesions was significantly reduced. 1 H-MRS showed reduced ratios of N-acetyl aspartate to creatinine (NAA/Cr) and NAA to choline (NAA/Cho) on day-20 as compared with the control values. Combining conventional MRI with DTI and MRS is valuable in the early diagnosis and prognosis of 1,2-DCE-induced encephalopathy.     

Capecitabine-induced acute toxic leukoencephalopathy

A 45-year-old woman was treated by Capecitabine (Xeloda^®) during 6 days for breast cancer with metastatic bone lesions when she presented with nausea, headaches, muscle cramps, dysarthria and swallowing disorders. A stroke was first suspected. Brain CT was normal. MRI showed bilateral and symmetric high signal intensities of deep white matter, corpus callosum and corticospinal tracts on diffusion-weighted imaging and T2 fluid-attenuated inversion recovery (FLAIR) sequence, similar to 5-FU acute leukoencephalopathy. An acute toxic leukoencephalopathy was diagnosed prompting to discontinue capecitabine, which allowed a regression of the symptoms. Though acute toxic leukoencephalopathies with pseudo-stroke presentation have been reported with other chemotherapy agents such as methotrexate or 5-fluorouracil (5-FU), cases of leukoencephalopathy induced by capecitabine are less reported and less well known. This oral precursor of 5-FU is commonly used to treat colorectal, stomach or breast cancers. Neurotoxicity of other 5-FU derivates like cormafur and tergafur have rarely been depicted as well.Although 5-FU-induced leukoencephalopathy is known, the potential toxicity of its precursor should be acknowledged as well. Early detection of chemotherapy-induced toxicity by MRI is crucial as symptoms may be reversible to the condition that chemotherapy is immediately discontinued.     

Toxic leukoencephalopathies

Leukoencephalopathy is a syndrome of neurologic deficits, including alteration of mental status, caused by pathologic changes in the cerebral white matter. The term, toxic leukoencephalopathy, encompasses a wide variety of exposures and clinical presentations. The diagnosis in these syndromes is made by careful attention to the history, clinical features, and radiologic findings. This article details three of the best-defined toxic leukoencephalopathies: delayed posthypoxic leukoencephalopathy, including delayed neurologic sequelae after carbon monoxide poisoning; heroin inhalation leukoencephalopathy; and posterior reversible encephalopathy syndrome.     

Increased frequency of JC virus type 2 and of dual infection with JC virus type 1 and 2 in Italian progressive multifocal leukoencephalopathy patients

To verify the possibility of different role of JC virus genotypes in the etiology of progressive multifocal leukoencephalopathy, we analysed several JC virus isolates amplified from AIDS patients with and without progressive multifocal leukoencephalopathy and healthy controls by nucleotide sequencing. Cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs) and urine from 52 AIDS patients suffering from various neurological diseases including 21 cases of progressive multifocal leukoencephalopathy, and PBMCs and urine from healthy subjects were evaluated by nested polymerase chain reaction (PCR) for the presence of DNA belonging to the highly conserved large T antigen (LT) of JC virus. The different JC virus subtypes were identified by nucleotide sequence analysis of the virion protein (VP1) genomic region. JC virus DNA was detected in all the CSF samples from the progressive multifocal leukoencephalopathy patients, but not in the CSF from non-progressive multifocal leukoencephalopathy cases, while the frequency of JC virus DNA detection in the PBMCs and urine did not differ among the three groups studied. JC virus type 2 was detected only in progressive multifocal leukoencephalopathy patients, and in particular in 52.4% of their CSF samples. Moreover, in the CSF of 19.0% of the progressive multifocal leukoencephalopathy cases, dual infection with both JC virus types 1 and 2 was found. The data obtained in this study indicate that the unexpected involvement of JC virus type 2, a strain not common in Italy, and the high frequency of dual infection with both JC virus types 1 and 2 in progressive multifocal leukoencephalopathy CSF, can be indications of risk factors for progressive multifocal leukoencephalopathy development.     

Methotrexate‐related leukoencephalopathy without radiation therapy: Distribution of brain lesions and pathological heterogeneity on two autopsy cases

This report concerns two rare autopsy cases of methotrexate (MTX)‐related leukoencephalopathy without radiation therapy. In the first case, there were widespread necrotic foci with prominent spheroids, that is, disseminated necrotizing leukoencephalopathy (DNL), mainly in the cerebral white matter. In contrast, in the second case, there were widespread demyelinated foci without significant axonal changes, which we would like to name disseminated demyelinating leukoencephalopathy (DDL), mainly in the cerebral white matter. We emphasize that the pathology of pure MTX‐related leukoencephalopathy is not uniform, and may show at least two kinds of histologic change. Furthermore, both cases did not develop significant vascular changes, which are usually induced by radiation therapy. The distribution of the lesions in two cases was examined by large specimens, including hemisphere specimens. The distribution of the lesions in the brain of our cases was also different. In the first case, the DNL lesions were predominantly distributed in the frontal and temporal lobes. In the second case, the DDL lesions were prominently localized in the occipital lobe. To our knowledge, this is the first report describing not only the pathological findings of MTX‐related leukoencephalopathy without irradiation but also the precise distributions of the lesions.     

Acute leukoencephalopathy after inhalation of a single dose of heroin

We describe extended and repeat magnetic resonance (MR) examinations in the case of a 16-year-old male who developed acute left-sided sensorimotor hemiplegia after a single dose of inhaled heroin. MRI revealed symmetrical hyperintense signals in T 2 -weighted images and massive diffusion disorders in the diffusion weighted images predominantly in parieto-occipital subcortical white matter and both ventral globi pallidi with preservation of U fibers and no brain oedema. MR spectroscopy data were compatible with combined hypoxic and mitochondrial damage resulting in axonal injury without demyelination. Normal values and variations had been obtained from spectra of five age-matched subjects. This is the first reported MR follow-up study of leukoencephalopathy occurring acutely after a first inhaled dose of heroin. We postulate that toxic spongiform leukoencephalopathy in heroin addicts may be the outcome of a complex mechanism directly triggered by heroin and causing mitochondrial as well as hypoxic injury in specific and limited areas of white matter.     

Conventional and diffusion-weighted MRI findings of methotrexate related sub-acute neurotoxicity

We describe longitudinal diffusion-weighted MRI findings of sub-acute leukoencephalopathy following methotrexate therapy in a 24-year-old man diagnosed with pre-B-cell acute lymphoblastic leukemia (ALL), presenting with right-sided paralysis and aphasia after second consolidation with intrathecal triple-drug therapy given intrathecally. This case demonstrates the value of DWI in evaluation and diagnosis of sub-acute toxic leukoencephalopathy in patients being treated with methotrexate. The longitudinal follow up DWI findings suggest reversible metabolic derangement rather than ischemia as the cause of these findings.     

Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15

Twelve patients with brain tumors and progressive edema caused by tumor progression or radiochemotherapy-related leukoencephalopathy were treated with H15, a phytotherapeutic anti-inflammatory agent. Edema was reduced in two of seven patients with glioblastoma with tumor progression and in three of five patients with treatment-related leukoencephalopathy. All patients with leukoencephalopathy improved clinically for several months.     

A model of methotrexate encephalopathy: neurotransmitter and pathologic abnormalities

Methotrexate may cause seizures, dementia, and leukoencephalopathy when given in toxic doses to children with leukemia or solid tumors. Even in therapeutic doses, treatment with this drug is associated with an increased incidence of seizures in children with leukemia. To study mechanisms of injury, juvenile rats were given multiple intraventricular injections of methotrexate and the brains were analyzed for histopathology and biogenic amine metabolites of dopamine and serotonin. Disruption of monoamine metabolism has been proposed as a cause of brain dysfunction from this chemotherapy. Multiple injections (1 or 2 mg/kg) produced convulsions in an increasingly larger percentage of animals at higher cumulative doses, and five doses produced the neuropathological changes seen in human leukoencephalopathy. A single dose reduced the concentration of brain metabolites of dopamine, but not serotonin, six hours later. The effect was less pronounced after five doses. This rodent model should be useful for studying the metabolic basis of methotrexate encephalopathy.     

Novel partial deletions,frameshift and missense mutations of CSF1R in patents with CSF1R-related leukoencephalopathy

Background and purpose

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is an adult-onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R-related leukoencephalopathy in association with clinical and imaging features.

Methods

Mutational analysis of CSF1R was performed for 100 consecutive patients with adult-onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long-read sequencing. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study.

Results

CSF1R mutations were identified in 15 patients, accounting for 15% of the adult-onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in-frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C-terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features.

Conclusions

Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R-related leukoencephalopathy.