BACKGROUND AND PURPOSE:Chronic kidney disease (CKD) is associated with brain dysfunction and an increased risk of cognitive impairment. However, it remains unclear whether functional hierarchical abnormalities are detectable in early-stage CKD and how they differ between early-stage and advanced non-dialysis CKD. MATERIALS AND METHODS:In this cross-sectional study, 96 patients with early-stage CKD (CKD1-3a), 80 patients with advanced CKD (CKD3b-5), and 75 healthy controls were enrolled. Resting-state functional magnetic resonance imaging data were analyzed using the functional connectivity gradient (FCG) framework to characterize stage-related alterations in cortical functional hierarchy. Associations among abnormal gradient metrics, Montreal Cognitive Assessment (MoCA) scores, and estimated glomerular filtration rate (eGFR) were further examined. RESULTS:Early-stage CKD showed limited abnormalities in FCG metrics, mainly involving reduced global principal gradient range and variance and lower gradient values in the default mode network. No significant regional differences remained after FDR correction in the direct comparison between early-stage CKD and healthy controls. In contrast, advanced CKD showed more extensive abnormalities across the global, network, and regional levels. In advanced CKD, abnormal principal gradient metrics were associated with lower eGFR and poorer cognitive performance. Cross-sectional statistical mediation analysis further suggested a possible indirect association pattern among renal dysfunction, reduced principal gradient range, and cognitive performance. CONCLUSIONS:Non-dialysis CKD is associated with stage-related alterations in functional brain hierarchy. Early-stage CKD is characterized by relatively limited abnormalities, whereas advanced CKD shows more widespread disruption. These findings support FCG metrics as promising neuroimaging markers of CKD-related alterations in brain functional organization.

PURPOSE:Metabolic disturbances are hallmark pathological features of Parkinson's disease (PD) and can be noninvasively captured by arterial spin labeling (ASL). However, the metabolic pattern of disconnections beyond regional alterations remains scarcely documented. We aimed to comprehensively investigate metabolic impairments in PD at the individual network scale by utilizing abundant hemodynamic metrics. METHODS:The multi-delay (m-ASL) was employed to obtain corrected cerebral blood flow (CBF), arterial cerebral blood volume and arterial transit time from groups of PD patients and healthy controls (HCs). For the comparison or cross-modality analysis, the uncorrected CBF and grey matter volume were also acquired via the ASL approach with single post-labeling delay (s-ASL) and T1 sequences, respectively. Metabolic similarity network (MSN) based on perfusion data and structural similarity network (SSN) were constructed for each individual, followed by analyses of connectivity, topology, classification and coupling. RESULTS:Metabolic similarity networks in patients with PD belong to small-world connectomes but exhibit decreased global integration and local segregation at the global level. The impairments in nodal centralities, modular architectures and connectivity strengths were diverse among MSNs. m-ASL improved the diagnostic efficiency of CBF-MSN by the CBF correction and further optimized the classification performance via the integration of all MSNs. Decoupling of SSN-MSN presented pathologically increased coefficients within subnetworks, deriving from altered metabolic and structural connectivity. CONCLUSION:Our study revealed the complex metabolic disconnections and SSN-MSN decoupling that underlie the complicated neurodegenerative process in PD, highlighting the clinical implications of m-ASL for comprehensive investigations of the metabolic pattern of disconnection syndromes.

The purpose of this study was to identify the perfusion pattern of choroid plexus (CP) impairment in patients with Parkinson’s disease (PD) and determine its relationship with the volume of the CP and its clinical relevance within the glymphatic system. Data from multidelayed arterial spin labeling (m-ASL), T1-weighted imaging, and diffusion tensor imaging were obtained from our consecutively enrolled patients with PD and matched healthy controls (HCs), followed by calculations of perfusion metrics, CP volume (CPV), and analysis along the perivascular space (ALPS) index and further statistical analyses. The pathological pattern of CP perfusion in PD patients included reduced cerebral blood flow (CBF) and arterial blood volume (aCBV) as well as increased CBF-arterial transit time (CBF–ATT) coupling (p < 0.05), which were significantly correlated with the CPV and ALPS indices (p < 0.05). Among the correlations with altered metrics, the linkages between CPV and perfusion metrics (CBF, aCBV, and CBF–ATT coupling) were specific to the PD group. Furthermore, the interactions between CBF and CPV and their clinical relevance to disease severity were mediated by the ALPS index (p < 0.05). These findings elucidate the diverse alterations in hemodynamics of CP and its mediating role within the glymphatic system in PD, underscoring further insights into glymphatic dynamics from the perspective of CP perfusion.

BACKGROUND:Parkinson's disease (PD) has been regarded as a disconnection syndrome with functional and structural disturbances. However, as the anatomic determinants, the structural disconnections in PD have yet to be fully elucidated.PURPOSE:To non-invasively construct structural networks based on microstructural complexity and to further investigate their potential topological abnormalities in PD given the technical superiority of diffusion kurtosis imaging (DKI) to the quantification of microstructure.MATERIAL AND METHODS:The microstructural data of gray matter in both the PD group and the healthy control (HC) group were acquired using DKI. The structural networks were constructed at the group level by a covariation approach, followed by the calculation of topological properties based on graph theory and statistical comparisons between groups.RESULTS:A total of 51 patients with PD and 50 HCs were enrolled. Individuals were matched between groups with respect to demographic characteristics (P >0.05). The constructed structural networks in both the PD and HC groups featured small-world properties. In comparison with the HC group, the PD group exhibited significantly altered global properties, with higher normalized characteristic path lengths, clustering coefficients, local efficiency values, and characteristic path lengths and lower global efficiency values (P <0.05). In terms of nodal centralities, extensive nodal disruptions were observed in patients with PD (P <0.05); these disruptions were mainly distributed in the sensorimotor network, default mode network, frontal-parietal network, visual network, and subcortical network.CONCLUSION:These findings contribute to the technical application of DKI and the elucidation of disconnection syndrome in PD.

Rationale and Objectives Parkinson's disease (PD) shows small structural changes in nigrostriatal pathways, which can be sensitively captured through diffusion kurtosis imaging (DKI). However, the value of DKI and its radiomic features in the classification performance of PD still need confirmation. This study aimed to compare the diagnostic efficiency of DKI-derived kurtosis metric and its radiomic features with different machine learning models for PD classification. Materials and Methods 75 people with PD and 80 healthy individuals had their brains scanned using DKI. These images were pre-processed and the standard atlas were non-linearly registered to them. With the labels in atlas, different brain regions in nigrostriatal pathways, including the caudate nucleus, putamen, pallidum, thalamus, and substantia nigra, were chosen as the region of interests (ROIs) to warped to the native space to measure the mean kurtosis (MK). Additionally, new radiomic features were developed for comparison. To handle the large amount of data, a statistical method called Z-score normalization and another method called LASSO regression were used to simplify the information. From this, a few most important features were chosen, and a combined score called Radscore was calculated using LASSO regression. For the comprehensive analyses, three different conventional machine learning models were then created: logistic regression (LR), support vector machine (SVM), and random forest (RF). To ensure the models were accurate, a process called 10-fold cross-validation was used, where the data were split into 10 parts for training and testing. Results Using MK alone, the models achieved good results in correctly identifying PD in the validation set, with LR at 0.90, RF at 0.93, and SVM at 0.90. When the radiomic features were added, the models performed even better, with LR at 0.92, RF at 0.95, and SVM at 0.91. Additionally, a nomogram combining all the information was created to predict the likelihood of someone having PD, which had an AUC of 0.91. Conclusion These findings suggest that the combination of DKI measurements and radiomic features can effectively diagnose PD by providing more detailed information about the brain's condition and the processes involved in the disease.

Parkinson's disease (PD) is manifested with disrupted topology of the structural connection network (SCN) and the functional connection network (FCN). However, the SCN and its interactions with the FCN remain to be further investigated. This multimodality study attempted to precisely characterize the SCN using diffusion kurtosis imaging (DKI) and further identify the neuropathological pattern of SCN-FCN decoupling, underscoring the neurodegeneration of PD. Diffusion-weighted imaging and resting-state functional imaging were available for network constructions among sixty-nine patients with PD and seventy demographically matched healthy control (HC) participants. The classification performance and topological prosperities of both the SCN and the FCN were analyzed, followed by quantification of the SCN-FCN couplings across scales. The SCN constructed by kurtosis metrics achieved optimal classification performance (area under the curve 0.89, accuracy 80.55 %, sensitivity 78.40 %, and specificity 80.65 %). Along with diverse alterations of structural and functional network topology, the PD group exhibited decoupling across scales including: reduced global coupling; increased nodal coupling within the sensorimotor network (SMN) and subcortical network (SN); higher intramodular coupling within the SMN and SN and lower intramodular coupling of the default mode network (DMN); decreased coupling between the modules of DMN-fronto-parietal network and DMN-visual network, but increased coupling between the SMN-SN module. Several associations between the coupling coefficient and topological properties of the SCN, as well as between network values and clinical scores, were observed. These findings validated the clinical implementation of DKI for structural network construction with better differentiation ability and characterized the SCN-FCN decoupling as supplementary insight into the pathological process underlying PD.

BackgroundEpilepsy (EP) is a common neurological disease in which 70-80% are thought to have a genetic cause. In patients with epilepsy, neurodevelopmental delay (NDD) was prevalent. Next generation of sequencing has been widely used in diagnosing EP/NDD. However, the diagnostic yield remains to be 40%-50%. Many reanalysis pipelines and software have been developed for automated reanalysis and decision making for the diseases. Nevertheless, it is a highly challenging task for smaller genetic centers or a routine pediatric practice. To address the clinical and genetic "diagnostic odyssey," we organized a Multidisciplinary Molecular Consultation (MMC) team for molecular consultation for 202 children with EP/NDD patients referred by lower level hospitals. MethodsAll the patients had undergone an aligned and sequential consultations and discussions by a "triple reanalysis" procedure by clinical, genetic specialists, and researchers. ResultsAmong the 202 cases for MMC, we totally identified 47 cases (23%) harboring causative variants in 24 genes and 15 chromosomal regions after the MMC. In the 15 cases with positive CNVs, 3 cases harbor the deletions or duplications in 16p11.2, and 2 cases for 1p36. The bioinformatical reanalysis revealed 47 positive cases, in which 12 (26%) were reported to be negative, VUS or incorrectly positive in pre-MMC reports. Additionally, among 87 cases with negative cases, 4 (5%) were reported to be positive in pre-MMC reports. ConclusionWe established a workflow allowing for a "one-stop" collaborative assessments by experts of multiple fields and helps for correct the diagnosis of cases with falsenegative and -positive and VUS genetic reports and may have significant influences for intervention, prevention and genetic counseling of pediatric epilepsy and neurodevelopmental disorders.

Patients with autoimmune encephalitis (AE) often developed psychiatric features during the disease course. Many studies focused on the psychiatric characteristic in anti-NMDAR encephalitis (NMDAR-E), but anti-LGI1 encephalitis (LGI1-E) had received less attention regarding the analysis of psychiatric features, and no study compared psychiatric characteristic between these two groups. The clinical data of AE patients (62 NMDAR-E and 20 LGI1-E) who developed psychiatric symptoms were analyzed in this study. In NMDAR-E, the most common higher-level feature was “behavior changes” (60/62, 96.8

AIMS:This study aimed to characterize the topological alterations and classification performance of high-order functional connectivity (HOFC) networks in cognitively preserved patients with Parkinson's disease (PD), relative to low-order FC (LOFC) networks.METHODS:The topological metrics of the constructed networks (LOFC and HOFC) obtained from fifty-one cognitively normal patients with PD and 60 matched healthy control subjects were analyzed. The discriminative abilities were evaluated using machine learning approach.RESULTS:The HOFC networks in the PD group showed decreased segregation and integration. The normalized clustering coefficient and small-worldness in the HOFC networks were correlated to motor performance. The altered nodal centralities (distributed in the precuneus, putamen, lingual gyrus, supramarginal gyrus, motor area, postcentral gyrus and inferior occipital gyrus) and intermodular FC (frontoparietal and visual networks, sensorimotor and subcortical networks) were specific to HOFC networks. Several highly connected nodes (thalamus, paracentral lobule, calcarine fissure and precuneus) and improved classification performance were found based on HOFC profiles.CONCLUSION:This study identified disrupted topology of functional interactions at a high level with extensive alterations in topological properties and improved differentiation ability in patients with PD prior to clinical symptoms of cognitive impairment, providing complementary insights into complex neurodegeneration in PD.

Leukoaraiosis (LA) is commonly found in aging healthy people but its pathophysiological mechanism is not entirely known. Furthermore, there is still a lack of effective pathological biomarkers that can be used to identify the early stage of LA. Our aim was to investigate the white matter structural network in asymptomatic patients with the early stage of LA. Tractography data of 35 asymptomatic patients and 20 matched healthy controls (HCs) based on diffusion kurtosis imaging (DKI) were analysed by using graph theory approaches and tract-based spatial statistics (TBSS). Diffusion parameters measured within the ALAs and HCs were compared. Decreased clustering coefficient and local efficiency values of the overall topological white matter network were observed in the ALAs compared with those of the HCs. Participants in the asymptomatic group also had lower nodal efficiency in the left triangular part of the inferior frontal gyrus, left parahippocampal gyrus, right calcarine fissure and surrounding cortex, right temporal pole of the superior temporal gyrus and left middle temporal gyrus compared to the ALAs. Moreover, similar hub distributions were found within participants in the two groups. In this study, our data demonstrated a topologic efficiency abnormalities of the structural network in asymptomatic patients with leukoaraiosis. The structural connectome provides potential connectome-based measures that may be helpful for detecting leukoaraiosis before clinical symptoms evolve.

Pathological process in Parkinson's disease (PD) is accompanied with functional and metabolic alterations. The time-varying properties of functional coherence and their coupling to regional perfusion are still rarely elucidated. To investigate early disruption of dynamic regional homogeneity (dReho) and neurovascular coupling in cognitively normal PD patients, dynamic neuronal synchronization and regional perfusion were measured using dReho and cerebral blood flow (CBF), respectively. Neurovascular coupling was assessed by CBF-ReHo correlation coefficient and CBF/ReHo ratio. Multivariate pattern analysis was conducted for the differentiating ability of each feature. Relative to healthy controls (HC) subjects, PD patients demonstrated increased dReho in middle temporal gyrus (MTG), rectus gyrus, middle occipital gyrus, and precuneus, whereas reduced dReho in putamen and supplementary motor area (SMA); while higher CBF/dReho ratio was located in putamen, SMA, paracentral lobule, and postcentral gyrus, whereas lower CBF/dReho ratio in superior temporal gyrus, MTG, precuneus, and angular gyrus (AG). Global and regional CBF-Reho decoupling were both observed in PD groups. The CBF/Reho ratio features achieved more powerful classification performance than other features. From the view of dynamic neural synchronization and neurovascular coupling, this study reinforced the insights into neural basis underlying PD and the potential role in the disease diagnosis and differentiation.

The neurophysiological basis of the association between interhemispheric connectivity and speech comprehension processing remains unclear. This prospective study examined regional cerebral blood flow (CBF), homotopic functional connectivity, and neurovascular coupling, and their effects on comprehension performance in post-stroke aphasia. Multimodal imaging data (including data from functional magnetic resonance imaging and arterial spin labeling imaging) of 19 patients with post-stroke aphasia and 22 healthy volunteers were collected. CBF, voxel-mirrored homotopic connectivity (VMHC), CBF-VMHC correlation, and CBF/VMHC ratio maps were calculated. Between-group comparisons were performed to identify neurovascular changes, and correlation analyses were conducted to examine their relationship with the comprehension domain. The correlation between CBF and VMHC of the global gray matter decreased in patients with post-stroke aphasia. The total speech comprehension score was significantly associated with VMHC in the peri-Wernicke area [posterior superior temporal sulcus (pSTS): r = 0.748, p = 0.001; rostroventral area 39: r = 0.641, p = 0.008]. The decreased CBF/VMHC ratio was also mainly associated with the peri-Wernicke temporoparietal areas. Additionally, a negative relationship between the mean CBF/VMHC ratio of the cingulate gyrus subregion and sentence-level comprehension was observed (r = -0.658, p = 0.006). These findings indicate the contribution of peri-Wernicke homotopic functional connectivity to speech comprehension and reveal that abnormal neurovascular coupling of the cingulate gyrus subregion may underly comprehension deficits in patients with post-stroke aphasia.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

OBJECTIVE The investigators aimed to explore the clinical characteristics, immunotherapy, and outcomes of patients with antileucine-rich glioma-inactivated-1 (anti-LGI1) encephalitis. METHODS Data on participants' clinical characteristics, laboratory findings, radiological and electroencephalogram (EEG) features, treatment, and outcomes from January 2012 to December 2016 were collected. Statistical analysis was conducted to assess the factors associated with patient functional outcome. Forty-three patients were enrolled in the study, with a predominance of males (65.1%). The median age at onset was 57 years (interquartile range [IQR]: 44.0-65.0). The median time from onset to diagnosis was 60 days (IQR: 37.0-127.0). RESULTS The main clinical manifestations included epilepsy (100%), faciobrachial dystonic seizures (FBDS; 44.2%), cognitive dysfunction (95.3%), neuropsychiatric disturbances (76.7%), sleep disorders (58.1%), and disturbance of consciousness (48.8%). Twenty-two patients (51.2%) had hyponatremia, 31 (72.1%) had abnormal EEG results, and 30 (69.8%) had abnormal brain MRI scans, mainly involving the hippocampus (76.7%) or temporal lobe (40%). Twenty of 34 patients (58.8%) in a follow-up MRI examination exhibited hippocampal atrophy. Twenty-five patients (58.2%) were administered corticosteroids and intravenous immunoglobulin, whereas 17 patients were treated only with corticosteroids. Forty-one patients (95.3%) had favorable outcomes after a median of 21.5 months (IQR: 7-43) of follow-up. Serum sodium level was a factor associated with a disabled status (odds ratio=0.81, 95% CI=0.66, 0.98, p=0.03). Anti-LGI1 encephalitis patients were characterized by seizures, FBDS, cognitive deficits, neuropsychiatric disturbances, and hyponatremia. CONCLUSIONS Most patients with anti-LGI1 encephalitis are nonparaneoplastic, have low recurrence rates, and have favorable prognostic outcomes. Rapid evaluation, prompt immunotherapy, and long-term follow-up are essential in the care of anti-LGI1 encephalitis patients.

Background: The complex crossing-fiber characteristics in the dual-stream system have been ignored by traditional diffusion tensor models regarding disconnections in post-stroke aphasia. It is valuable to identify microstructural damage of crossing-fiber pathways and reveal accurate fiber-specific language mapping in patients with aphasia. Methods: This cross-sectional study collected magnetic resonance imaging data from 29 participants with poststroke aphasia in the subacute stage and from 33 age- and sex-matched healthy controls. Fixel-based analysis was performed to examine microstructural fiber density (FD) and bundle cross-section alterations of specific fiber populations in crossing-fiber regions. Group comparisons were performed, and relationships with language scores were assessed. Results: The aphasic group exhibited significant fixel-wise FD reductions in the dual-stream tracts, including the left inferior fronto-occipital fasciculus (IFOF), arcuate fasciculus, and superior longitudinal fasciculus (SLF) III (family-wise-error-corrected p < 0.05). Voxel- and fixel-wise comparisons revealed mismatched distributions in regions with crossing-fiber nexuses. Fixel-wise correlation analyses revealed significant associations between comprehension impairment and reduced FD in the temporal and frontal segments of the left IFOF, and also mapped naming ability to the IFOF. Average features along the whole course of dominant tracts assessed with tract-wise analyses attributed word-level comprehension to the IFOF (r = 0.723, p < 0.001) and revealed a trendlevel correlation between sentence-level comprehension and FD of the SLF III (r = 0.451, p = 0.021). The mean FD of the uncinate fasciculus (UF) and IFOF correlated with total and picture naming scores, and the IFOF also correlated with responsive naming subdomains (Bonferroni corrected p < 0.05). Conclusions: FD reductions of dual streams suggest that intra-axonal volume reduction constitutes the microstructural damage of white matter integrity in post-stroke aphasia. Fixel-based analysis provides a complementary method of language mapping that identifies fiber-specific tracts in the left hemisphere language network with greater specificity than voxel-based analysis. It precisely locates the precise segments of the IFOF for comprehension, yields fiber-specific evidence for the debated UF-naming association, and reveals dissociative subdomain associations with distinct tracts.

To explore large‐scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico-subcortical circuitry subserving naming processing, although neurovascular regulation of the non-dominant thalamic and basal ganglia subregions underlying post-stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age-, sex-, and education-matched healthy volunteers were analyzed. Region-of-interest-wise functional connectivity (FC) was calculated to measure the strength of cortico-subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico-subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right-hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend-level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha-pSTS connectivity in the non-dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo-cortical circuits in post-stroke aphasia. This study highlights the neurovascular pathophysiology of the non-dominant hemisphere and demonstrates thalamic involvement in naming after stroke.

Objectives: This study described the clinical characteristics of autoimmune neurological diseases with dual seropositive antibodies of CASPR2 and LGI1. Patients and Methods: Three patients, with antibodies targeting both CASPR2 and LGI1 (EUROIMMUN, FA 112d1, Germany), hospitalized in Department of Neurology, Xuanwu Hospital, Capital Medical University from June 2016 to June 2019 were collected in this study. We summarized the clinical characteristics of patients with CASPR2 and LGI1 antibodies from a targeted literature review. Results: Three patients reported were all middle-aged and elderly male with diverse neurological symptoms, including seizures, psychological abnormalities, limb weakness and hyperhidrosis. Interestingly, three patients displayed three different clinical syndromes (isolated epilepsy, Morvan syndrome and limbic encephalitis, respectively). White blood cell and glucose in Cerebrospinal fluid (CSF) were normal and CSF for protein was slightly elevated. Electromyography (EMG) showed abnormal spontaneous firing in case 2. Brain magnetic resonance imaging (MRI) revealed bilateral hyper-intensity of the temporal lobe on T2 and FLAIR sequence in case 3. Cancer screening program of patient 2 showed thymoma. Cell based assay was positive in serum for both LGI1 and CASPR2 antibodies, while these antibodies were negative in CSF. They were treated with glucocorticoid or intravenous immunoglobulin (WIG). Followed up for 6 months to 1 year, all patients got remission to different extent. Conclusion: Through the detailed analysis of three patients, the combination of both antibodies contributes to a broad spectrum of neurological symptoms in the central, peripheral, and autonomic nervous systems. The patients with same antibodies can have different clinical syndromes. Early tumor screening and immunotherapy will improve the prognosis of the disease.

目的 基于2015年诊断标准分析视神经脊髓炎谱系疾病(NMOSD)患者的临床特点和影像学特征.方法 回顾性分析120例NMOSD患者的临床特点、影像学特征、以及对比水通道蛋白4(AQP4)抗体阳性和阴性患者的临床异同点.结果 女性∶男性=2.75∶1,平均发病年龄37.1岁,平均病程21个月,80％患者为复发病程.起病症状视神经炎和脊髓炎分别占41.7％和40％.15.8％患者伴有自身免疫病;5.8％患者伴有内分泌疾病.78.1％的患者AQP4抗体阳性,抗体阳性组疾病严重程度评分显著高于抗体阴性组(P =0.026).长节段横贯性脊髓炎占83.7％.头部MRI异常见于36.7％ (44/120)患者.28.3％ (34/120)患者脑脊液白细胞升高(＞5×106/L),脑脊液蛋白49.5 mg/dl(正常值:15 ～45 mg/dl);30.8％ (37/120)患者寡克隆区带阳性;52.2％ (24/46)患者髓鞘碱性蛋白阳性;40％ (48/120)患者脑脊液免疫球蛋白G升高.结论 2015年诊断标准有助于NMOSD诊断,NMOSD长节段脊髓炎多见,短节段脊髓炎不能排除NMOSD,AQP4抗体阳性患者病情更重,应重视早期诊断.

BACKGROUND:Short transverse myelitis (STM) is considered uncommon in neuromyelitis optica spectrum disorders (NMOSD). Poor recognition of STM occurring in NMOSD may lead to increased delay in diagnosis and appropriate treatment.OBJECTIVES:The aim of this study was to assess the frequency and characteristics of STM in Chinese patients with NMOSD.METHODS:We enrolled 91 patients with NMOSD based on the 2015 International Consensus Diagnostic Criteria for NMOSD. The patients were divided into STM group and longitudinally extensive transverse myelitis (LETM) group according to the length of initial spinal cord lesions at the initial myelitis manifestation of NMOSD.RESULTS:Initial STM was observed in 18 patients (18/91, 19.8%). The STM episode was the first manifestation of NMOSD in 9 patients (50%) and preceded by optic neuritis in 3 patients (16.7%), area postrema syndrome in 5(27.8%) and brainstem syndrome in 1(5.6%). Compared to the NMOSD patients with an initial LETM, patients with STM suffered less motor and bowel or bladder disability, had minor EDSS at clinical onset, but suffered earlier relapse (P＜.05). Thirteen patients had single short spinal lesion (13/18, 72.2%) and 5 patients had two short lesions. Of the 23 STM lesions, 4 lesions spanned 2.5 vertebral segments, 12 showed a length of continuous 2 vertebral segments, 7 were confined to single vertebral segment. The lesions on axial imaging involved the central grey matter in 61.1% (11/18) patients with STM and in 95.9%（70/73）patients with LETM (P＜.05). Both the patients with STM（50%）and LETM (34.2%) had brain lesions.CONCLUSIONS:Initial STM does not exclude consideration of NMOSD diagnosis.