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Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.
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<p><b>BACKGROUND</b>Although there were criteria for diagnosis of neuromyelitis optica (NMO) and multiple sclerosis (MS), it is still difficult to differentiate NMO from MS, due to the overlapping clinical manifestations. Therefore it is necessary to characterize clinical features of NMO and MS patients in the mainland of China, to simplify the process of disease diagnosis, and to identify criteria for the differential diagnosis of NMO and MS.</p><p><b>METHODS</b>A total of 138 Chinese Han patients from the mainland of China including 73 NMO, 60 MS and 5 MS-like patients with positive NMO-IgG were included in the study. Clinical records were reviewed retrospectively and the results of clinical examination, laboratory experiments, magnetic resonance imaging (MRI) and evoked potentials (EPs) were compared between NMO and MS patients. In addition, the relationship between the NMO-IgG serologic status and clinical characteristics were analyzed.</p><p><b>RESULTS</b>Compared with MS patients (1.3: 1.0), more female prevalence was observed in NMO patients (4.2: 1.0; P = 0.003). There were also statistically significant differences in visual EPs, oligoclonal bands, brainstem lesions in MRI and longitudinally extensive spinal cord lesions (LESCLs) between NMO and MS patients. Brainstem lesions observed in brain MRI were found in 17.9% of MS patients, over 3.7 times higher than in NMO patients (4.8%, P = 0.024). When stratified NMO patients by NMO-IgG, LESCLs were found in 42.1% of NMO-IgG-negative NMO patients, over 3.5 times higher than in NMO-IgG-positive patients (11.9%, P = 0.008). Statistical difference was also observed in CD4+/CD8+ ratios between NMO-IgG-positive and -negative NMO patients.</p><p><b>CONCLUSIONS</b>Comprehensive analysis of MRI, laboratory and EPs data can facilitate differential diagnosis of MS and NMO. In addition, the combination of LESCLs and brain MRI findings failing to satisfy MRI criteria for MS is highly sensitive and specific for NMO.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , China , Magnetic Resonance Imaging , Multiple Sclerosis , Diagnosis , Neuromyelitis Optica , Diagnosis , Retrospective StudiesABSTRACT
Objective To screen the mutation and analysis its characteristics of SPG4 and SPG3A in Chinese patients with hereditary spastic paraplegia (HSP).Methods Mutation and polymorphism of the SPG4 and SPG3A were screened in the index eases of 26 autesomal dominant families (AD-HSP) and 30 sporadic cases by combination of DHPLC and sequencing analysis, then the index cases of 26 AD-HSP were further confirmed with direct sequencing.Results One novel mutation of SPG4, 1616 + 1g→t, was identified in the index ease from an AD-HSP family.Three symptomatic patients and 2 pre-symptomatic patients were found in this family by sequencing analysis.No mutation of SPG3A was detected.In addition, 8 novel SPG4 polymorphisms and 3 novel SPG3A polymorphisms were identified.Conclusions The study has broadened the mutation and polymorphism spectrums of SPG4 and SPG3A.Mutation of these two genes is less common in this group of patients.