To evaluate changes in cerebral interstitial fluid dynamics following whole-brain radiotherapy (WBRT) for brain metastases using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, and to investigate the relationship between these changes and the subsequent development of radiation-induced leukoencephalopathy (LEP). A retrospective analysis was conducted on 50 patients who underwent WBRT for brain metastases. Baseline and post-WBRT DTI-ALPS indices were compared using paired t-tests. Univariate and multivariate linear regression analyses were performed to assess the relationship between changes in the DTI-ALPS index and clinical- and treatment-related factors. In a subset of 33 patients, univariate and multivariate logistic regression analyses were conducted to explore the association between the percentage change in the DTI-ALPS index and the development of LEP at 6-month follow-up, after adjustment for relevant clinical- and treatment-related factors. The mean DTI-ALPS index decreased significantly following WBRT (baseline: 1.487±0.257; post-WBRT: 1.353±0.229; p<0.001). A higher baseline DTI-ALPS index was significantly associated with a greater decline in the index post-WBRT (p=0.023). In the logistic regression analysis, a greater percentage reduction in the DTI-ALPS index was the only factor significantly associated with LEP development at 6 months (p=0.048). WBRT is associated with impaired cerebral interstitial fluid dynamics, as reflected by a significant reduction in the DTI-ALPS index. A greater decline in the DTI-ALPS index was predictive of LEP development, suggesting its potential utility as a biomarker for early diagnosis of radiation-induced LEP.

A 7-year-old male diagnosed case of B-cell acute lymphoblastic leukemia, intermediate risk group, central nervous system Status 1, received the first dose of methotrexate (2 g/m 2 ) as consolidation.Serum methotrexate level at 42 h was <0.1 mmol/L and leucovorin rescue was administered as per protocol.On day 5 of therapy, he developed generalized tonic-clonic seizures without associated with any fever.The patient was started on Inj levetiracetam.His hemogram showed hemoglobin 9.6 g/dL, total leukocyte count 2100/cumm (N35% L60% M9% E5%), and platelets 76,000/cumm.Biochemistry revealed normal results of renal and liver function tests; serum electrolytes were also within normal limits.A computed tomography scan of the brain revealed no abnormality.Magnetic resonance imaging revealed hyperintensities with diffusion restriction in the bilateral deep white matter region [Figure 1a and b].A diagnosis of methotrexate-induced leukoencephalopathy (LE) was made based on clinical and characteristic radiological features.The patient became symptom-free by 2 days and methotrexate was omitted from further courses of consolidation.Common causes of seizures in a leukemic child include stroke, infections, metabolic abnormalities, or cancer itself.Methotrexate-induced LE should

Stereotactic Radiosurgery as an Effective and Safe Treatment Modality in Central Nervous System Lymphoma, a Single Institution Experience

The HIT-SKK protocol is used for low/standard-risk medulloblastomas in young children with the aim to eliminate cranial irradiation and its neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders. This study describes the risk factors and course of LE, and investigates its correlation with neurocognitive impact. A retrospective, multicenter study was conducted in 35 children under 5 years old, with a median follow-up of 72 months (range 14 to 130). The main analysis was performed in 30 patients who received cumulative doses of MTX as per-protocol (group 1). Five patients who received higher cumulative doses of MTX were analyzed separately. All follow-up MRIs and NP assessments were centrally reviewed by experts. Twenty patients in group 1 developed LE, grade 2 and 3 abnormalities did not correlate with higher cumulative doses of ITV-MTX (p = 0.698). Considering the most recent NP evaluation, the Full-Scale IQ (FSIQ) and Wechsler indices were in the average to lower average range. The FSIQ was deficient in 6/17 evaluable patients. Cumulative dose of ITV-MTX was almost associated with decreased processing speed competence (p = 0.055) which was the most frequently impaired neurocognitive domain. Neuropsychological assessment scores were not statistically lower in patients with persistent grade 2 LE at the end of follow-up. This study described that the use of cumulative dose of MTX (IV and ITV) according to the HIT-SKK protocol resulted in LE that tented to decrease over time, without significant correlation with a decline in neuro-intellectual skills.

BACKGROUND: HIT-SKK protocol is used for the treatment of low risk medulloblastomas in young children with the aim of eliminating cranial irradiation and its long-term side effects, in particular neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders.The objectives are to describe the risk factors and the course of LE, and to investigate its impact on long-term neurocognitive and behavioural outcome. METHODS: A French retrospective, multicenter study including 35 children under 5 years of age, treated between 2009 and 2017, with a median follow up of 72 months. All follow-up MRIs including assessment of the severity of the LE (Fazekas and CTCAE grading) and all NP evaluations were centrally rewieved. RESULTS: 25/34 evaluable patients presented a LE during follow up, in a median delay of 2 months (1 - 17 months) after the start of chemotherapy. Grade 2 and 3 abnormalities were correlated with higher cumulative dose of ITV -MTX (p=0,01). Full Scale IQ (FSIQ) and Wechsler indexes were in the average or low average of the reference population. FSIQ was deficient in 7/20 evaluable patients. Processing speed (PSI) was the most frequently impaired neurocognitive domain: 9/20 patients with borderline or very low score, all having received a significantly higher cumulative dose of ITV-MTX (p=0,04). A decrease in overall NP scores was observed in patients for whom grade 2 or 3 LE persisted at the end of follow-up with an average FSIQ estimated at 82.1 (SD 16.9) versus 94.2 (SD 20.6). This decrease was significant for PSI (p=0,049). LE and neurocognitive impairments were not correlated with a younger age at diagnosis. CONCLUSION: This study confirmed the responsibility of MTX, and in particular ITV-MTX therapy in the onset and, most often, persistence of LE and its association with neurocognitive disorders.

Обоснование. Ранее неоднократно сообщали об эффективности внутривенной иммуноглобулинотерапии у некоторых детей с расстройствами спектра аутизма без уточнения критерия отбора потенциальных ответчиков на иммунотерапию. Цель исследования: оценить эффективность и безопасность высокодозовой иммуноглобулинотерапии при расстройствах аутистического спектра у детей с генетическим дефицитом фолатного цикла. Материалы и методы. Исследуемую группу составили 78 детей в возрасте от 2 до 10 лет, которые принимали в/в иммуноглобулин в дозе 2 г/кг/мес на протяжении 6 месяцев. В контрольную группу вошли дети аналогичного возрастного и гендерного распределения, которые получали лишь немедикаментозную реабилитационную поддержку. Выявляли замены нуклеотидов MTHFR677 С &gt; Т, MTHFR1298 А &gt; С, MTRR A/G и MTR A/G в различных комбинациях методом полимеразной цепной реакции. Динамику психических симптомов оценивали при помощи шкалы Aberrant Behavior Checklist. Результаты и обсуждение. Достигнуто полное устранение фенотипа расстройств аутистического спектра у 21 пациента и выраженная положительная динамика еще у 33 детей исследуемой группы (p &lt; 0,05; Z &lt; Z0,05). Параллельно отмечалась положительная динамика со стороны других клинических проявлений фенотипа дефицита фолатного цикла: PANDAS (у 19 из 21), эпилептического (у 29 из 36) и кишечного (у 49 из 68 детей) синдромов (p &lt; 0,05; Z &lt; Z0,05). Не отмечено положительной динамики со стороны симптомов поражения пирамидных путей (p &gt; 0,05; Z &gt; Z0,05). Отмечено снижение суммарной вирусной нагрузки и повышение количества естественных киллеров в крови (p &lt; 0,05; Z &lt; Z0,05). Почти полное устранение симптомов лейкоэнцефалопатии в исследуемой группе отмечалось у 29 пациентов, а выраженная положительная динамика — еще в 24 случаях (p &lt; 0,05; Z &lt; Z0,05). Выводы. Внутривенный иммуноглобулин оказывает комплексное положительное воздействие на проявления генетического дефицита фолатного цикла, включая расстройства спектра аутизма, экстрапирамидные нарушения, кишечный синдром, эпилептиформную активность мозга, иммунодефицит и лейкоэнцефалопатию.

Simple SummaryIn this study, we investigated standardized post-chemotherapy magnetic resonance (MR) scans for leukoencephalopathy and patient- and treatment-related risk factors in childhood leukemia patients. As prevalence numbers are limited, our study provides the required estimations for this population. Furthermore, we demonstrate that younger patients might be more at-risk for development of leukoencephalopathy (LE), and that a higher intravenous methotrexate (IV-MTX) dose has a cumulative toxic effect, while the number of intrathecal administrations was not significantly associated with the extent of LE. This can suggest we should modify chemotherapeutic treatment regimens by decreasing the number of IV-MTX applications, with special attention for younger patients.Methotrexate (MTX) is associated with leukoencephalopathy (LE) in children treated for lymphoblastic leukemia/lymphoma (ALL/LBL). However, large-scale studies with systematic MR acquisition and quantitative volumetric lesion information remain limited. Hence, the prevalence of lesion burdens and the potential risk factors of LE in this population are still inconclusive. FLAIR-MRI scans were acquired at the end of treatment in children who were treated for ALL/LBL, which were quantitatively analyzed for LE. Voxels were assigned to the lesion segmentation if indicated by two raters. Logistic and linear regression models were used to test whether lesion presence and size were predicted by risk factors such as age at diagnosis, gender, intrathecal (IT-) or intravenous (IV-)MTX dose, CNS invasion, and acute neurological events. Patients with a pre-existing neurological condition or low-quality MR scan were excluded from the analyses. Of the 129 patients, ten (8%) suffered from CNS invasion. Chemotherapy-associated neurological events were observed in 13 patients (10%) during therapy, and 68 patients (53%) showed LE post-treatment. LE was more frequent in cases of lower age and higher cumulative IV-MTX doses, while the extent of LE and neurological symptoms were associated only with IV-MTX doses. Neurological events were not significantly associated with LE, even though symptomatic patients demonstrated a higher ratio of LE (n = 9/13) than asymptomatic patients (n = 59/116). This study suggests leukoencephalopathy frequently occurs in both symptomatic and asymptomatic leukemia patients. Younger children and patients treated with higher cumulative IV-MTX doses might need more regular screening for early detection and follow-up of associated sequelae.

In archived diffusion tensor imaging (DTI) studies, a reversed-phase encoding (PE) scan required to correct the distortion in single-shot echo-planar imaging (EPI) may not have been acquired. Furthermore, DTI tractography is adversely affected by incorrect white matter segmentation due to leukoencephalopathy (LE). All these issues need to be addressed. To propose and evaluate a modified DTI processing pipeline with DIstortion COrrection using pseudo T2 -weighted images (DICOT) to overcome limitations in existing acquisition protocols. Retrospective feasibility. DICOT was assessed in simulated data and 84 acute lymphoblastic leukemia (ALL) patients with reversed PE acquired. The pipeline was then tested in 522 scans from 261 ALL patients without a reversed PE acquired. A 3 T; diffusion-weighted EPI; 3D magnetization prepared rapid acquisition gradient echo (MPRAGE). Repeated measures analysis of variance and Tukey post hoc tests were performed to compare fractional anisotropy (FA) values obtained by different methods. FA and corresponding absolute error maps were obtained using TOPUP, DICOT, INVERSION (Inverse contrast Normalization for VERy Simple registratION) and NO CORR (no correction). Each method was assessed by comparing to TOPUP. The pipeline in the ALL patients was evaluated based on the failure rate of the distortion correction using the global correlation values. Using DICOT reduced the mean absolute errors by an average of 32% in FA in simulation datasets. In 84 patients, the error reductions were approximately 15% in FA with DICOT, while it was 5% with INVERSION. No significant differences between the TOPUP and DICOT were observed in FA with P=0.090/0.894(AP/PA). Only 15 of 516 examinations requiring any additional manual intervention. This modified pipeline produced better results than the INVERSION. Furthermore, robust performance was demonstrated in archived patient scans acquired without an inverse PE necessary for TOPUP correction. 3 TECHNICAL EFFICACY: Stage 2.

Genetic leukoencephalopathies are inherited disorders characterized by progressive white matter involvement. Although most are paediatric conditions, late-onset adult leukoencephalopathies are being increasingly recognized. Adult leukoencephalopathies may present as neurodegenerative diseases with cognitive decline and motor symptoms. Similar to their paediatric counterparts, different adult leukoencephalopathies often have distinctive MRI appearances. In particular, DWI has been recently shown to demonstrate specific patterns of persistent diffusion restriction in several adult-onset leukoencephalopathies. As such, DWI may provide important clues to the diagnosis of adult-onset leukoencephalopathy. The purpose of this review is to discuss characteristic DWI features in some late-onset leukoencephalopathies.

The most common form of pediatric cancer is acute lymphoblastic leukemia (ALL). Magnetic resonance (MR) neuroimaging studies have revealed leukoencephalopathy (LE) in pediatric ALL, but the impact of LE on long-term neurocognitive performance remains unknown. This study aims to objectively characterize the prevalence, extent, and intensity of LE, and their association with later neurocognitive performance. Pediatric patients (N = 377) treated for ALL without irradiation underwent MR neuroimaging at 4 time points throughout therapy (end of remission induction [MR1], end of consolidation [MR2], and week 31 [MR3] and week 120 [end therapy, MR4] of continuation treatment) and neurocognitive evaluations at the end of therapy and 2 years later. Generalized estimation equation models with logit link were developed to explore the association between LE prevalence and extent with time points throughout therapy, age at diagnosis (≤5 years or >5 years), treatment risk arm (low risk or standard/high risk), and sex. General linear models were also developed to investigate the association between neuroimaging metrics during treatment and neurocognitive performance at 2-year follow-up. The prevalence of LE was greatest (22.8%, 74/324) after consolidation therapy. The prevalence of LE increased at MR2 relative to MR1 regardless of treatment risk arm (both P's < 0.001), age group (both P's < 0.001), or sex (male, P < 0.001; female, P = 0.013). The extent of white matter affected also increased at MR2 relative to MR1 regardless of treatment risk arm (standard/high risk, P < 0.001; low risk, P = 0.004), age group (both P's < 0.001), or sex (male, P < 0.001; female, P = 0.001). Quantitative relaxation rates were significantly longer in LE compared with that in normal-appearing white matter in the same examination (T1, P < 0.001; T2, P < 0.001). The LE prevalence early in therapy was associated with increased parent ratings of conduct problems (P = 0.039) and learning difficulties (P = 0.036) at 2-year follow-up compared with that at the end of therapy. A greater extent of LE early in therapy was associated with decreasing performance on a measure of processing speed (P = 0.003) from the end of therapy to 2-year follow-up. A larger extent of LE at the end of therapy was associated with decreased performance in reading (P = 0.004), spelling (P = 0.003), and mathematics (P = 0.019) at 2-year follow-up and increasing problems with attention (omissions, P = 0.045; β, P = 0.015) and memory (list A total recall, P = 0.010) at 2-year follow-up compared with that at the end of therapy. In this large cohort of pediatric patients treated for ALL without irradiation, asymptomatic LE during therapy can be seen in almost a quarter of patients, involves as much as 10% of the white matter volume, and is associated with decreasing neurocognitive performance, increasing parent reports of conduct problems, and learning difficulties in survivors.

There is no abstract availble.

Objective: To summarize the clinical and imaging features of five patients of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with cysteine-sparing NOTCH3 gene missense mutations and explore potential pathogenicity of gene mutations. Methods: The clinical data from five patients who were admitted to the People’s Hospital of Zhengzhou University from March 2017 to November 2018 were collected. The patients were found to carry cysteine-sparing NOTCH3 gene mutations through genetic testing and diagnosed pathologically. They were probands confirmed from five unrelated family and all five patients were performed full exon detection and skin biopsy. Results: Genetic testing identified five patients with cysteine-sparing NOTCH3 gene missense mutations, a total of five different mutations, including p.R75Q, p.D80G, p.V237M, p.S1418L and p.R1761H. The first three mutations were found in the epidermal growth factor-like repeats (EGFr), the latter two mutations near the transmembrane domain. Granular osmiophilic material was identified in all cases examined with skin biopsy. The age at initial symptom onset of these five cases was ranged from 22 to 58 years and three cases presented cardiovascular risk factors. The primary clinical manifestations included migraine in one case, ischemic stroke in three cases, psychiatric disturbances in four cases, cognitive dysfunction in five cases, while gait disturbance, pseudobulbar palsy, and seizures accounted for only one case each. Magnetic resonance imaging of five patients all showed white matter hyperintensities (WMLs) and lacunar infarcts, and WMLs involved the anterior temporal pole and external capsules in three cases separately. According to the criteria proposed by Muiño et al for evaluating the pathogenicity of cysteine-sparing NOTCH3 mutations, all five mutations are potentially pathogenic. Conclusions: Most characteristics of CADASIL patients with cysteine-sparing NOTCH3 gene mutations are similar to those of CADASIL patients with cysteine NOTCH3 gene mutations. Mutations not involving the EGFr may also have potential pathogenicity, and the specific mechanism still needs further study.

Objective To investigate the clinical features, imaging features, pathological features and gene diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Methods Clinical manifestations, signs and imaging characteristics of a female patient hospitalized in the First Affiliated Hospital of Zhengzhou University for more than 10 days due to headache were analyzed, and skin biopsy and HTRA1 and Notch3 gene detection were performed. The pedigree of the proband was investigated in detail, and HTRA1 gene test and related imaging examination were conducted in parallel. Due to the deceased parents of the patient, relevant genetic testing could not be conducted. A control group of 100 healthy people were analyzed. Results The clinical manifestations of proband were headache after insomnia, hearing loss in the right ear, easy to wake up and sweat at night. Brain MRI showed diffuse patchy long T1 and long T2 signals in bilateral fronto-parietal temporal occipital insula, internal and external capsule areas, bilateral basal ganglia areas, and bilateral thalamus. Fluid attenuated inversion recovery sequence showed high signals. Magnetic sensitive weighted imaging showed scattered patchy low signals in bilateral cerebral and cerebellar hemispheres, bilateral basal ganglia area, left thalamus and brain stem. The proband had consanguineous parents. A homozygous mutation C to T transition at position 589 (c.589C>T) was found in exon 3 of HTRA1 gene with the proband and both siblings. The heterozygous c.589C>T mutation appeared in another sister of the proband. Under the light microscope of skin biopsy, pigmentation in the basal layer of the skin could be seen, collagen fiber hyperplasia in the dermis was accompanied by a small amount of inflammatory cell infiltration, and no definite amyloidosis was found. No mutations were found in Notch3 gene. Because the patient′s parents were deceased, genetic testing was not possible. One hundred healthy controls had no such mutation. Conclusions The CARASIL family with HTRA1 gene c.589C>T homozygous mutation was reported, and the pathogenicity of the mutation was confirmed. HTRA1 genetic testing is recommended for diagnosis and differential diagnosis of CARASIL with family history or clinical suspicion. Key words: Cerebrovascular disorders; Genetic testing; Mutation; Pedigree; CARASIL; HTRA1 gene

Objective To analyze the clinical features of patients with sporadic adult-onset neuronal intranuclear inclusion disease (NIID), and raise awareness of the disease among medical workers. Methods The clinical data of two patients with pathologically confirmed adult sporadic NIID, admitted to our hospital in February 2018 and October 2018, were collected. The clinical manifestations, head MR imaging, cutaneous pathological features, treatments and prognoses were retrospectively analyzed. Results Both patients were characterized with slow progressive dementia, accompanied with diverse clinical manifestations involving the central and autonomic nervous systems. Acute encephalopathic signs occurred in both patients. Head MR imaging showed extensive leukoencephalopathy mainly in the frontal and parietal lobes; these white matter abnormalities showed hyperintensity in T2-weighted imaging and liquid attenuated inversion recovery sequences, and equal or low signal in T1-weighted imaging. Remarkably, specific curve-like high-intensity signals along the corticomedullary junction in the bilateral frontal lobe were both observed in diffusion-weighted imaging. Patient 2 with seizures showed unilateral cerebral cortical edema on head MR imaging. In both patients, skin biopsy revealed specific eosinophilic inclusion bodies in the nucleus of some sweat gland cells, adipocytes and fibroblasts. Patient one was treated with dexamethasone intravenous drip to relieve headache and vision loss, and cognitive therapy was given. The acute encephalopathy of patient two was relieved by intravenous gamma globulin. Conclusions NIID has various clinical manifestations of central, peripheral, and autonomic nerve systems. Head MR imaging characteristic changes and skin pathological biopsy contribute to the diagnosis. Immunomodulatory therapy may be effective for acute encephalopathic symptoms in NIID. Key words: Neuronal intranuclear inclusion disease; Dementia; Acute encephalopathy; Leukoencephalopathy; Skin biopsy

Purpose: Aim of the present study was to identify potential safety signals for the six newer disease-modifying therapies (DMTs) for multiple sclerosis using the FDA Adverse Events Reporting System (FAERS) database. Methods: A case/non-case study was conducted with data from spontaneous reports submitted in FAERS between 2004 and 2018, using the OpenVigil2.1-MedDRA. Daclizumab, natalizumab integrin, alemtuzumab dimethyl fumarate, fingolimod, teriflunomide were examined. Adverse events were selected by the Summary Product Characteristics of the products, including all frequency levels. The reporting odds ratio (ROR) was used to express the association between DMTs and reporting adverse events. Results: Currently approved DMTs share some common side effects such as increased risk for infections (especially progressive multifocal leukoencephalopathy and herpes virus infections), risk for neoplasms (basal and squamous cell carcinoma, kaposi's sarcoma) and blood disorders (lymphopenia, leukopenia, pure red cell aplasia) which were confirmed by our analysis. Conclusion: This disproportionality analysis strengthens the already knowledge about the safety of DMTs for multiple sclerosis and emerges some new potential safety signals.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by localized neuronal loss, and the presence of eosinophilic intranuclear inclusions in neurons and glial cells. Biopsy samples of skin, rectal and sural nerve showed hyaline intranuclear inclusions. Reported NIID cases showed familial type according to family history, and three clinical subgroups (infantile, juvenile and adult form) according to onset and disease duration. NIID has been considered as a heterogeneous disease because of the highly variable clinical manifestations including cognitive dysfunction, parkinsonism, cerebellar ataxia, peripheral neuropathy and autonomic dysfunction. Additionally, some NIID cases presented episodes of conscious disturbance, cognitive decline, movement disorder or even fever. Head magnetic resonance imaging of some patients revealed symmetrical leukoencephalopathy in T2 image and fluid attenuated inversion recovery image and high intensity signal in corticomedullary junction in diffusion weighted image. But it is not the only abnormal finding of imaging, and other diseases may also present the similar changing. Other diseases including fragile X-associated tremor-ataxia syndrome, Huntington′s disease and spinocerebellar ataxia should be considered in differential diagnosis. Key words: Neuronal intranuclear inclusion disease; Neurodegenerative disease; Dementia; Peripheral neuropathy; Fragile X-associated tremor-ataxia syndrome

对武汉市儿童医院风湿免疫科收治确诊的2例全身型幼年特发性关节炎(sJIA)并可逆性后部白质脑病综合征(PRES)的临床特点和影像学资料进行回顾性分析。2例病例原发病均为sJIA，病程期间有并发巨噬细胞活化综合征(MAS)，均曾用环孢素、甲泼尼龙冲击治疗及长期口服泼尼松治疗。起病时间：1例为原发病起病后半年，1例为原发病起病后1个月。临床表现：2例均急性起病，且血压较高，头痛伴抽搐1例，头痛伴神志不清1例。头颅磁共振成像：1例脑桥及双侧枕顶叶脑实质在T2序列、T2液体衰减反转恢复(FLAIR)及弥散加权成像(DWI)见片状、脑回状高信号灶，界线不清；脑室系统未见明显扩大，脑沟稍宽；1例双侧顶枕叶见多发小片状稍长T2信号影，FLAIR及DWI序列呈高信号影，DWI序列未见弥散受限。双侧侧脑室稍大，枕大池大。经积极降血压、降颅内压、营养神经对症治疗，1例治疗后72 h临床症状好转，1例治疗7 d后临床症状好转。表明sJIA在治疗过程中可合并PRES，临床表现和头颅影像学特点多样，应提高对该病的认识，早期发现，及时治疗，以改善治疗效果和预后。

Progressive multifocal leukoencephalopathy (PML) is caused by JC virus and is associated with cancers and immunosuppressive therapies. PML has no

Objective To summarize the phenotypic spectrum of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Fujian population, evaluate the efficiency of the scale and try to adjust it. Methods Thirty-eight CADASIL patients and 64 CADASIL-like patients were recruited based on the CADASIL scale and gene tests, who visited the First Affiliated Hospital of Fujian Medical University and Fujian Neurology Research Institute from May 2011 to November 2017. Their clinical and neuroimaging characteristics were analyzed. Results The migraine, migraine with aura, transient ischemic attack/stroke, early onset age, psychiatric disturbances, cognitive decline, leukoencephalopathy, subcortical infarcts showed no statistically significant differences between the two groups. Instead, compared with CADASIL-like patients (10/64, 15.6%; 47/64,73.4%; 10/64, 15.6%), CADASIL patients demonstrated higher percentages of temporal pole involvements (13/38, 34.2%; χ2=4.716, P=0.030), external capsule involvements (36/38, 94.7%; P=0.008) and family history in at least two generations (13/38, 34.2%; χ2=4.716, P=0.030). According to the scale, the scores showed statistically significant difference between CADASIL (14.84±3.03) and CADASIL-like patients (13.34±3.31; t=2.282, P=0.025) with an area under receiver operating characteristic curve of 0.622. Conclusions CADASIL showed no specific symptoms in Fujian population. The neuroimaging features were proposed to be focused on, especially the external capsule involvements. CADASIL scale could improve diagnostic efficiency, but still needs to be adjusted for Fujian population. The weight value of migraine, migraine with aura and cognitive decline was suggested to be decreased. Key words: CADASIL; Phenotype; Genetic testing

Objective To explore the clinical and neuroimaging features in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) caused by mutation of the colony stimulating factor 1 receptor gene (CSF1R). Methods The proband and another patient from a HDLS pedigree were assessed respectively through standardized clinical evaluation (medical history inquiry, physical examination), neuropsychology assessment, MRI, genetic sequencing, as well as brain PET imaging with carbon11-labelled Pittsburgh compound-B (11C-PIB) . Results A HDLS pedigree with three patients was recruited to this study. Apathy, memory decline, slow behavior were the first symptoms for two of the patients. Being bedridden, urinary incontinence and epilepsy were developed at the later stage. A missense mutation c.2381T>C (p. I794T) in exon 18 of the CSF1R gene of chromosome 5 was identified in the proband. The brain DWI illustrated multiple patchy high signal in periventricular white matter and centrum semiovale which was characterized by persistence, and the corpus callosum was affected in the early stage. Conclusion The multiple patchy high signal with persistence in periventricular white matter and centrum semiovale of DWI is helpful for the early diagnosis of HDLS. Key words: Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids; Colony stimulating factor 1 receptor gene; Mutation