BackgroundDespite existing treatments of ocular myasthenia gravis (OMG), there remains a need for more effective therapies with fewer side effects. Telitacicept, a novel agent that simultaneously inhibits B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), represents a promising therapeutic candidate for OMG.Case presentationIn this study, telitacicept monotherapy or combination therapy was administered to three patients with OMG who had shown an inadequate response to, or were intolerant of, standard treatments. All patients demonstrated clinically significant improvement post-treatment. Specifically, both the Myasthenia Gravis Foundation of America-Quantitative Myasthenia Gravis (MGFA-QMG) and the Myasthenia Gravis Activities of Daily Living (MG-ADL) scores showed a marked reduction, indicating decreased disease severity and improved quality of life. Immunological assessments revealed an initial decline in CD19+ B lymphocyte counts and acetylcholine receptor (AChR) antibody levels. Interestingly, despite well-controlled clinical symptoms, AChR antibody levels subsequently rebounded and stabilized. Furthermore, pulmonary infections in one patient were not established as causally related to telitacicept.ConclusionTelitacicept monotherapy or combination treatment in OMG was associated with favorable clinical improvement and a mild adverse event profile, and its use can be tailored to the individual patient. However, larger-scale and longer-term studies are necessary to confirm these findings and fully establish the role of telitacicept in OMG management.

GRN mutations act as causative factors in patients with FTD clinical phenotype or FTD pathology and exhibit high clinical heterogeneity. The discovery of these mutations and the analysis of their associations with resembling Alzheimer’s disease should be critical to understand the pathogenesis of FTD. Clinical analysis, neuroimaging, target region capture and high-throughput sequencing were performed in a family of 3 generations. The underlying Alzheimer’s pathology was evaluated by using biomarker evidence obtained from cerebrospinal fluid (CSF) amyloid testing, 18F-florbetapir (AV-45) PET imaging and FDG18-positron emission tomography imaging. Through target region capture and high-throughput sequencing, a three-generation family was able to identify a heterozygous G to A point mutation at position 490 (c.1468)G > A, which led to a valine to methionine substitution (V490M) at exon 12. This unique missense mutation was found at codon 1468. Eight members of the proband's family—two sisters and the proband himself—had the mutation found by Sanger sequencing. Interestingly, biomarker tests for amyloid in the proband's cerebrospinal fluid (CSF) indicated pathology consistent with Alzheimer's disease (AD). The mutation was expected to have a high likelihood of being pathogenic. We firstly reported a novel mutation in the GRN gene at codon 490 (V490M) in exon 12 in a China FTD family. The CSF biomarker alterations of the proband revealed a reduction in Aβ42 and the Aβ42/Aβ40 ratio. The analysis of mutation might support the role of GRN in patients with FTD and contribute to the discovery of a new pathological mechanism underlying the disease.

BackgroundPrimary angiitis of the central nervous system (PACNS) is a rare immune-mediated vasculitis with distinct subtypes (large/medium-vessel [LV-PACNS] and small-vessel [SV-PACNS]). This study aims to provide evidence-based data from the Chinese population for improving the subtype-specific management system of PACNS.MethodsThis retrospective single-center study enrolled 47 PACNS patients (29 with SV-PACNS, 18 with LV-PACNS) who met the 1988 Calabrese and Mallek diagnostic criteria, with a follow-up duration ≥1 year. Clinical phenotypes, imaging characteristics, treatment, prognosis, and factors influencing prognosis were retrospectively analyzed in both groups.ResultsCompared with LV-PACNS, SV-PACNS had more severe initial neurological impairment (baseline modified Rankin Scale mRS score: 3 vs. 2, p=0.043) and a longer median time from onset to treatment initiation (154 days vs. 58.5 days, p=0.013). In terms of clinical features, LV-PACNS had a higher incidence of cerebrovascular events (88.9% vs. 58.2%, p=0.027) and limb weakness/sensory abnormalities (83.3% vs. 34.5%, p=0.001), while SV-PACNS had a higher incidence of tumor-like lesions (41.4% vs. 5.6%, p=0.008). Imaging features showed that 100% of LV-PACNS patients had cerebrovascular stenosis, of which 94.4% exhibited circumferential vascular wall enhancement; and compared with SV-PACNS, they had a higher incidence of ischemic infarction (66.7% vs 20.7%, p=0.002). Multivariate analysis confirmed that time from onset to treatment was an independent risk factor for poor 1-year prognosis (mRS score > 2) in both subtypes (SV-PACNS: OR = 1.012, p=0.021; LV-PACNS: OR = 1.048, p=0.040).ConclusionsThis study identified the core clinical and neuroimaging differences between LV-PACNS and SV-PACNS, and pointed out that treatment delay are the main issues affecting prognosis.

ObjectiveThe aims of the study were to characterize the clinical manifestations and outcomes of patients with antibody-negative severe autoimmune encephalitis (AE).MethodsThis retrospective, monocentric study recruited patients from the Neurology Department of Henan Provincial People’s Hospital between April 2017 and December 2023. All patients underwent neural antibody testing in both blood and cerebrospinal fluid (CSF) and met the diagnostic criteria for autoantibody-negative but probable severe AE, with available 1-year follow-up data.ResultsIn total, 124 patients with autoantibody-negative severe AE were analyzed. Among them, 27.4% achieved good functional outcomes at discharge. Older age (OR 1.034, 95% confidence interval [CI] 1.010-1.058, p = 0.004) and the presence of dyskinesia/dystonia (OR 8.463, 95% CI 3.282-21.820, p < 0.001) were predictive of poor short-term outcomes. At the 1-year follow-up, 54.8% experienced favorable long-term outcomes. Independent predictors of unfavorable long-term outcomes included older age (OR 1.076, 95% CI 1.018-1.136, p = 0.009), longer hospital stays (OR 1.264, 95% CI 1.105-1.446, p = 0.001), the presence of refractory status epilepticus (OR 14.765, 95% CI 1.759-123.935, p = 0.013) and higher CASE scores at discharge (OR 2.079, 95% CI 1.450-2.980, p < 0.001). Additionally, 30.6% of patients had relapsed, with refractory status epilepticus being an independent risk factor for relapse.ConclusionAlthough patients with antibody-negative severe AE experience significant disability in the early stages of their disease, the majority eventually regain independent functioning. Older age at disease onset, longer hospital stays, the presence of refractory status epilepticus and higher CASE scores at discharge may predict a poor long-term prognosis.

The Cardiometabolic Index (CMI) represents a novel anthropometric measurement, which combines characteristics of adiposity and lipids. Since obesity, lipid metabolism, and inflammation may collectively facilitate the occurrence of stroke, we hypothesize that a combination of elevated levels of the CMI and high-sensitivity C-reactive protein (hs-CRP) increases the risk of future stroke among middle-aged and older Chinese adults. This study included 8,973 participants aged 45 years or older from the China Longitudinal Study on Health and Retirement (CHARLS), who were stroke-free and underwent baseline evaluations between 2011 and 2012, with followed-up at 2013, 2015 and 2018. The exposures were CMI and hs-CRP, with CMI calculated using the formula [waist circumference (cm)/height (cm)] × [triglycerides (mmol/L)/HDL-C (mmol/L)]. The primary outcome was the occurrence of new-onset stroke events. Cox proportional hazards models and restricted cubic spline (RCS) analyses were conducted to examine the associations between CMI, hs-CRP, and their combined effects on stroke risk. Sensitivity analysis was further implemented to verify the robustness of the results. A total of 629 participants (7.01

ObjectiveThe Clinical Assessment Scale for Autoimmune Encephalitis (CASE) is a novel tool tailored specifically for evaluating the severity of autoimmune encephalitis (AE). However, its application in severe AE patients is limited. This study aimed to evaluate the reliability and validity of the CASE and explore its clinical significance in a severe AE cohort.MethodsThe relevant clinical characteristics, laboratory data, and prognosis of patients diagnosed with severe AE between April 2017 and April 2023 were collected. The CASE and modified Rankin scale (mRS) were performed at admission, discharge, and 1-year follow-up, respectively. The reliability of CASE was validated by calculating the Cronbach’s alpha value. The validity was evaluated by calculating the Spearman’s rank correlation with the corresponding mRS. Univariate and multivariate logistic regression were utilized to identify risk factors for poor prognosis.ResultsA total of 140 patients were recruited for the study. The CASE scale presented great internal consistency, with Cronbach’s α value of 0.768 for the total score. The Spearman’s rank correlation analysis revealed strong criterion validity between CASE and mRS, with coefficients of 0.68, 0.92, and 0.95 at admission, discharge, and 1-year follow-up, respectively (all p < 0.001). ROC analysis identified CASE score at admission served as a promising predictive marker for clinical response to treatment, with an AUC of 0.67 (95% CI: 0.57-0.77, p = 0.003). The optimal cut-off point was 22.5. At 1-year follow-up, 72/140 (51.4%) patients achieved good functional status (mRS, 0-2). Multivariate logistic regression confirmed that higher CASE scores on admission and older age at onset were associated with poor short-term as well as 1-year prognosis, respectively. In addition, no clinical response to treatment (OR = 40.499; 95% CI: 7.077-231.746, p < 0.001) and longer duration of hospitalization (OR = 1.071; 95% CI: 1.017-1.128, p = 0.010) were associated with poor function states at 1-year follow-up.ConclusionThe CASE has proven suitable for evaluating disease severity and prognosis in severe AE patients. Besides, CASE score, age at disease onset, hospital stays, and response to immunotherapy are identified as independent risk factors for unsatisfactory prognosis in severe AE patients.

AimRed blood cell distribution width-to-albumin ratio (RAR) is a combined new indicator reflecting immunology and has been reported to predict the prognosis of inflammation-related diseases and brain diseases. However, the association and predictive value of RAR in the prognosis of patients with autoimmune encephalitis (AE) has not been reported.MethodsThis was a retrospective cohort study, and data were collected from the Henan Provincial People’s Hospital. RAR was categorized according to quartile. The prognosis was assessed using the modified Rankin Scale (mRS), and an mRS score of ≥3 was defined as a poor prognosis. The logistical regression model was used to explore the association between RAR and the prognosis, with results reported as odds ratio (OR) and 95% confidence interval (CI). The predictive value of RAR was evaluated by calculating the area under the receiving operating curve (AUC), sensitivity, specificity, and accuracy.ResultsA total of 175 eligible patients were included for analysis, and 51 patients were identified as having poor prognosis. After adjusting age, cancer, other diseases, histological subtype, antiepileptic therapy, anti-tumor treatment, ICU treatment, and length of stay, RAR in the highest quartile (Q4) was found to be significantly associated with the high odds of poor prognosis (OR = 5.63, 95%CI: 1.98–16.02) compared to RAR in the lowest quartile (Q1). In addition, RAR was identified as a predictor for the prognosis of AE patients (AUC = 0.660, 95%CI: 0.574–0.746).ConclusionThis study found the close association and predictive value of RAR for the prognosis of AE patients, indicating that RAR might help clinicians identify high-risk populations.

Introduction:This study aims to explore the clinical features and prognostic factors for relapse of acute disseminated encephalomyelitis (ADEM) in adults.Material and methods:56 patients with ADEM were retrospectively analyzed. The epidemiological characteristics, clinical manifestations, laboratory features, magnetic resonance imaging (MRI), treatment and prognosis data of these patients were analyzed using the χ2 test for categorical variables and Mann-Whitney U-test for continuous variables. Then, the clinical characteristics and recurrence factors were summarized.Results:56 patients with ADEM, based on the criteria of the International Pediatric Multiple Sclerosis Study Group, were recruited to the study. Among these patients, 31 were male and 25 were female. Furthermore, 13 patients had multiphasic ADEM, and 29 patients (52%) had definite incentive factors before onset. The commonest presenting symptoms and signs were fever (36%), disturbance of consciousness (52%), mental disorder (38%), seizure (14%), headache and dizziness (43%), optic neuritis (34%), autonomic nervous system symptoms (43%), limb paralysis or abnormal sensation (73%), and unilateral or bilateral pyramidal tract signs (48%). Inflammatory changes in the cerebrospinal fluid were prominent. MRI T2-weighted and fluid-attenuated inversion recovery images displayed multiple or large flaky high signals, and the lesions were usually different in the number and distribution of these lesions. Intravenous corticosteroids and/or immunoglobulin were still important treatments in the acute phase. After treatment, 38 patients completely recovered, 9 patients had neurologic deficits, and 9 patients died.Conclusions:ADEM in adults is not uncommon, its clinical features are complex and varied, and some of these are multiphasic. There may be some potential clinical predictors at first onset.

目的:探讨直窦血栓形成并硬脑膜动静脉瘘(dural arteriovenous fistula,DAVF)的临床表现、影像学特点、治疗及预后,以提高临床医师对二者合并病例的认识.方法:结合文献,回顾性分析直窦血栓形成并致双侧丘脑病变患者的年龄、性别、临床症状、影像学特点、治疗及预后.结果:通过中国知网、万方、维普和PubMed数据库检索到国内外发表的关于直窦血栓形成并硬脑膜动静脉瘘致双侧丘脑病变,并本文中1例,共36例.其中男性32例,女性4例,平均年龄56.7岁.临床共同点为不同程度的认知功能下降,MRI通常表现为双侧丘脑T2或FLAIR高信号.25例接受血管内栓塞治疗,其中4例行2次或以上治疗;4例行外科手术夹闭;其中3例血管内栓塞不完全,联合外科手术夹闭;3例给予脱水降颅压联合抗凝药物保守治疗;1例单纯脱水降颅压.32例行手术治疗的患者中,3例症状改善,28例症状明显好转,1例死亡;保守治疗患者中3例失访,1例出院时稍好转.结论:以双侧丘脑受累的疾病种类众多,经积极治疗仍缓解不明显患者,且MRI提示双侧丘脑肿胀者,需考虑直窦血栓形成并硬脑膜动静脉瘘,尽早完善全脑血管造影检查明确诊断,条件允许者尽快完善各种手术治疗,逆转受损的神经功能.

Objective:To report 8 patients of sporadic Creutzfeldt-Jakob disease (sCJD) with real-time quaking-induced conversion (RT-QuIC) positive and analyze their clinical characteristics.Methods:The medical records of patients discharged from Henan Provincial People′s Hospital from January 2018 to May 2021 who were diagnosed with clinically probable sCJD and had RT-QuIC test were retrospectively analyzed. General information (gender, age, initial symptom, main clinical manifestations), accessory examination [brain magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid 14-3-3 protein, prion protein gene, antibodies related to autoimmune encephalitis and paraneoplastic syndrome] were collected. By a telephone-based follow-up survey, data about morality and total duration of course were collected. The patients were divided into two groups according to electroencephalogram, 14-3-3 protein, duration of disease and MRI results, and the differences of fluorescence peak time and fluorescence peak value in RT-QuIC results between groups were compared.Results:Among 8 patients, 7 patients had subacute onset and 1 patient had chronic onset. Main clinical manifestations included progressive cognitive decline (8/8), pyramid sign (5/8), walking instability (4/8), mental and behavior disorder (4/8), myoclonus (4/8), akinetic mutism (4/8), dizziness (3/8), limb shaking (2/8), dysarthria (2/8), visual hallucination (1/8), impaired vision (1/8). All cases had abnormal electroencephalogram and typical periodic sharp slow compound waves (PSWCs) were observed in 5 cases. Brain MRI showed high signal intensity in the cerebral cortex and/or basal ganglia on diffusion-weighted imaging in 7 cases, of which 6 cases involved bilateral basal ganglia. Cerebrospinal fluid 14-3-3 protein was positive in 2 cases, and RT-QuIC was positive in all cases. The fluorescence peak time of RT-QuIC was shorter in patients with PSWCs [(7.617±2.164) h vs (10.602±2.247) h, t=2.84, P=0.010] and high total MRI score [ (7.600±1.907) h vs (9.760±2.457) h, t=2.26, P=0.032]. Conclusions:RT-QuIC detection is a reliable method for early diagnosis of sCJD. RT-QuIC results were related to PSWCs and degree of MRI involvement.

CNS Neuroscience & TherapeuticsVolume 28, Issue 9 p. 1464-1468 LETTER TO THE EDITOROpen Access Vasculitic Moyamoya syndrome in a patient with paroxysmal nocturnal hemoglobinuria: A case report and literature review Fangfang Li, Fangfang Li orcid.org/0000-0003-1485-4261 Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorMingrong Xia, Mingrong Xia Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorHongyu Li, Hongyu Li Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorDan Li, Dan Li Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorDan Guo, Dan Guo Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorWeizhou Zang, Corresponding Author Weizhou Zang tiger_zang@163.com Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China Correspondence Weizhou Zang and Jiewen Zhang, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, China. Emails: tiger_zang@163.com (W.Z.); zhangjiewen9900@126.com (J.Z.)Search for more papers by this authorJiewen Zhang, Corresponding Author Jiewen Zhang zhangjiewen9900@126.com Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China Correspondence Weizhou Zang and Jiewen Zhang, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, China. Emails: tiger_zang@163.com (W.Z.); zhangjiewen9900@126.com (J.Z.)Search for more papers by this author Fangfang Li, Fangfang Li orcid.org/0000-0003-1485-4261 Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorMingrong Xia, Mingrong Xia Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorHongyu Li, Hongyu Li Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorDan Li, Dan Li Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorDan Guo, Dan Guo Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, ChinaSearch for more papers by this authorWeizhou Zang, Corresponding Author Weizhou Zang tiger_zang@163.com Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China Correspondence Weizhou Zang and Jiewen Zhang, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, China. Emails: tiger_zang@163.com (W.Z.); zhangjiewen9900@126.com (J.Z.)Search for more papers by this authorJiewen Zhang, Corresponding Author Jiewen Zhang zhangjiewen9900@126.com Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China Correspondence Weizhou Zang and Jiewen Zhang, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, China. Emails: tiger_zang@163.com (W.Z.); zhangjiewen9900@126.com (J.Z.)Search for more papers by this author First published: 11 July 2022 https://doi.org/10.1111/cns.13891AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Dear Editor, Moyamoya syndrome (MMS) is a chronic and progressive occlusive cerebrovascular disease characterized by steno-occlusive changes at or around terminal carotid arteries or the initial segments of the anterior/middle cerebral arteries accompanied by the development of fragile collateral network, which is often secondary to an underlying acquired or inherited condition. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell genetic mutation disease manifesting as hemolytic anemia, marrow failure, smooth muscle dystonia, and thrombosis.1 MMS secondary to PNH is rarely reported in the literature.1-4 However, to the best to our knowledge, there has been no direct evidence about the vasculitic moyamoya changes of intracranial arteries in the situation of PNH. Here, we provide the direct evidence using intracranial high-resolution vessel wall imaging (vw-MRI) to present this phenomenon in our patient and discuss its possible cause and treatment. A 42-year-old woman was admitted to Henan Provincial People's Hospital with a 20-day history of clumsy movement of her right hand and slurred speech for 1 day. Initially diffusion weighted imaging (DWI) of the brain showed acute ischemic stroke in left frontoparietal lobe when she showed clumsy movement of her right hand 20 days earlier (Figure 1A). In the meanwhile, magnetic resonance angiography (MRA) indicated stenosis in the proximal part of bilateral middle cerebral artery (MCA), moderate-to-severe stenosis in left internal carotid artery (ICA) and A1 segment of left anterior cerebral artery (ACA) (Figure 1B). Laboratory examination indicated moderate macrocytic anemia (Hemoglobin 6.6 g/dL, mean corpuscular volume 108 fL) and high values of lactate dehydrogenase (LDH, 1672 U/L). The patient denied any family history of cerebrovascular disease and no obvious vascular risk factors were found. However, a history of PNH (flow cytometry showed CD55 negative equal to 21.41% of the erythrocytes, CD59 negative equal to 28.16% of the erythrocytes, CD55 negative equal to 86.42% of the granulocytes, CD59 negative equal to 84.73% of the granulocytes) was reported and hemolytic attacks occurred occasionally. Aspirin (100 mg per day) and rosuvastatin (10 mg per day) was administered and her symptoms improved gradually. One day before her admission, the patient presented with weakness of her right upper limb and slurred speech. In addition, the second brain DWI revealed multiple acute cerebral infarctions in right frontal regions and extended ischemic lesions in left frontoparietal lobe (Figure 1C). On physical examination, power was 2/5 in right upper limb and 4/5 in the other three limbs. During the second day, laboratory examinations demonstrated the patient had slight macrocytic anemia with a hemoglobin of 8.5 g/dL with the mean corpuscular volume of 116.4 fL, LDH 1702 U/L, total bilirubin 31.8umol/L, direct bilirubin 10.5 μmol/L and indirect bilirubin 21.3 μmol/L. Dual antiplatelet therapy (Aspirin 100 mg per day and clopidogrel 75 mg per day) and intensive lipid-lowering treatment (rosuvastatin 20 mg per day) were started. Vw-MRI was then conducted and revealed smooth, homogeneous, concentric arterial wall thickening and enhancement in left ICA. Meanwhile, vw-MRI also showed steno-occlusive lesions in the petrous segment, distal communicating segment of left ICA and formation of moyamoya vessels (Figure 2A–D). The patient's situation worsened gradually during hospitalization. In the eleventh day on her admission, deteriorative mental status leading to somnolence, aphasia and recurrent intermittent episodes of dystonia were observed. Physical examination showed active tendon reflexes in all extremities and bilateral Babinski signs were positive. Routine blood test was performed immediately and showed that hemoglobin dropped to 6.7 g/L. Brain magnetic resonance imaging (MRI) was repeated on twelfth day after admission and manifested bilateral frontotemporal lobes and basal ganglia acute ischemic lesions (Figure 2E–F). Considering the exacerbation of patient's cerebral infarction, intermittent episodes of hemolytic events, and vasculitic changes of intracranial arteries, intravenous methylprednisolone (500 mg/d for 3 days) was prescribed, with doses decreased gradually over time. Following the treatment, her consciousness started to improve and could make eye contact with her families. Intermittent episodes of dystonia tapered as well. Twenty-fourth day after her admission, the patient developed difficulties in breathing and decreased blood oxygen saturation. Pulmonary artery computed tomography angiography (CTA) was then conducted and displayed multiple thrombosis in bilateral pulmonary arteries (Figure 2I). In the meanwhile, ultrasound found thrombosis in the intermuscular vein of the right lower extremity. Then antiplatelet therapy was replaced by low molecular weight heparin (5000 IU, Q12H, IH) and the patient's respiratory symptoms improved soon. Thirty-second day on her admission, brain MRI was reexamined, and no new lesions were found (Figure 2G–H). Pulmonary arteries thrombus also disappeared on forty-third day after admission (Figure 2J). The patient could partially cooperate with the instructions and hemoglobin raised to 8.9 g/L when discharged from hospital. FIGURE 1Open in figure viewerPowerPoint (A) Initially axial DWI of brain showed acute infarction in left frontoparietal lobe (long white arrow). (B) MRA demonstrated vascular stenosis in the proximal part of bilateral MCA, moderate to severe stenosis in left ICA, A1 segment of left ACA and proximal segment of posterior cerebral artery (PCA) (short white arrow). (C) The second axial brain DWI revealed multiple acute cerebral infarctions in right frontal regions and extended ischemic lesions in left frontoparietal lobe (long white arrow) FIGURE 2Open in figure viewerPowerPoint (A, B) Sagittal vw-MRI showed smooth, homogeneous, concentric arterial wall thickening and enhancement in left ICA. (C, D) Axial MRA revealed the development of fragile collateral network. (E, F) Bilateral frontotemporal lobes and basal ganglia acute ischemic lesions were presented on twelfth day after admission. (G, H) Brain MRI was performed on thirty-second day after admission and no new lesions appeared. (I) Representative image of pulmonary CTA showed thrombosis in left pulmonary arteries. (J) Pulmonary CTA was repeated before discharge and thrombosis in left pulmonary arteries was vanished However, we knew from a telephone follow-up that she died suddenly at home 2 months later. DISCUSSION We provide a vw-MRI image that directly supports vasculitic moyamoya changes of intracranial arteries in the situation of PNH for the first time, as far as we know. In our case report, the patient was diagnosed with PNH 3 years before her cerebral artery thrombosis, and hemolytic attacks occurred from time to time. Except PNH, the young patient has no family history of cardiovascular diseases or cerebrovascular risk factors. The first cerebral ischemic attack and subsequent stroke progression were both accompanied with hemolytic events (a reduction of hemoglobin as well as an increase of LDH and indirect bilirubin), which suggest a possible causal relationship between PNH and cerebral infarction. Next, vw-MRI showed homogeneous, concentric arterial wall thickening and enhancement in terminal portions of left ICA and proximal segment of MCA, which indicated vasculitic moyamoya vessels in the patient.5 As complement activation, increased free hemoglobin, endothelial dysfunction and inflammatory reaction are the main pathological mechanisms of PNH, while the abovementioned pathological mechanisms also play major roles in vascular inflammation and heme can cause vascular inflammation followed by vascular obstruction,6 we presume that the patient's vasculitic moyamoya syndrome may be a result of PNH. Paroxysmal nocturnal hemoglobinuria is a rare acquired bone-marrow disease featured by deficiency of glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins such as CD55 and CD59 on membrane of erythrocytes, leading to an increased sensitivity of red blood cells to membrane attack complex. It characteristically presents as hemolytic anemia, hemoglobinuria and intravascular thrombosis. Arterial thrombosis is an infrequent complication of PNH, accounting for approximately 15% of total thromboembolism events, which located primarily in cerebral vasculature (90.7%).7 To date, there were only four reports which described moyamoya phenomenon in PNH patients.1-4 Among these patients, their ages ranged from 9 to 52 years old, and there were two males and two females. Except one little boy who received eculizumab treatment and had a good prognosis, the remaining three patients all presented with recurrent cerebral infarction and responded differently to antiplatelet therapy, which were detailed depicted in Table 1. However, none of these reports provided direct evidence about the vasculitic moyamoya changes of intracranial arteries in PNH patients. In our case report, except the vasculitic moyamoya changes, the patient also presented with multiple cerebral infarction, pulmonary artery thrombosis, as well as intermuscular vein of the right lower extremity. Antiplatelet therapy seems cannot stop the progression of thrombosis further certified hypercoagulable state in PNH,6 which reminds clinical physicians that anticoagulant remedy may be a superior choice in PNH patients with thrombosis event (if no contraindication). Besides, as cerebral blood flow is an important marker for clinical prognosis of moyamoya syndrome and sensitive to small blood pressure changes,8 it is necessary to monitor cerebral blood flow and maintain a strict blood pressure control in daily medical work. TABLE 1. Clinical characteristics of patients with moyamoya syndrome and PNH reported in the literature Patient Age Gender Duration of disease Hemoglobin concentration when neurological symptoms occurred (g/L) Treatment Follow-up Mugikura et al3 52 Female 5 months 88, 77 Antiplatelet 2 years. No additional infarction, and no progression of the steno-occlusive lesions Lin et al2 11 Female 1 year and 10 month 40, −, − Prednisolone, coumadin, and washed red blood cell transfusion No follow-up information Yen et al4 9 Male - 76 Eculizumab No cerebrovascular accidents recurred Cheng et al5 21 Male 12 years 50, 73 Aspirin, prednisolone, and washed red blood cell 1 year. Lost the ability to work for deteriorating weakness of the right limbs. Our patient 42 Female 3 years 66, 85, 67 Dual antiplatelet therapy, prednisolone, washed red blood cell. Then antiplatelet therapy was replaced by anticoagulant therapy soon 2 months. Died at home For the treatment of PNH associated vasculitic moyamoya syndrome, complement inhibitor such as Eculizumab to cope with PNH and reduce PNH relevant complications is the first choice,9 corticosteroid or immunosuppressive therapy may be an alternative strategy.10 Surgical revascularization seems to be a more advanced and effective option for ischemic moyamoya syndrome. ACKNOWLEDGMENTS This project was supported by the National Natural Science Foundation of China (82171196). CONFLICT OF INTEREST The authors declare no conflict of interest. DATA AVAILABILITY STATEMENT Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. CONSENT FOR PUBLICATION Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this journal. All authors agreed to publication. 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Intracranial Vessel Wall MRI: principles and expert consensus recommendations of the American Society of Neuroradiology. AJNR Am J Neuroradiol. 2017; 38(2): 218- 229. CrossrefCASPubMedWeb of Science®Google Scholar 6Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013; 121(25): 4985- 4996. quiz 5105. CrossrefCASPubMedWeb of Science®Google Scholar 7Tabib A, Karbian N, Mevorach D. Demyelination, strokes, and eculizumab: lessons from the congenital CD59 gene mutations. Mol Immunol. 2017; 89: 69- 72. CrossrefCASPubMedWeb of Science®Google Scholar 8Liming Z, Weiliang S, Jia J, et al. Impact of blood pressure changes in cerebral blood perfusion of patients with ischemic Moyamoya disease evaluated by SPECT. J Cereb Blood Flow Metab. 2021; 41(6): 1472- 1480. CrossrefPubMedWeb of Science®Google Scholar 9Kulesekararaj A, Risitano AM, Maciejewski JP, et al. Phase 2 study of Danicopan in paroxysmal nocturnal hemoglobinuria patients with an inadequate response to eculizumab. Blood. 2021; 138(20): 1928- 1938. CrossrefPubMedWeb of Science®Google Scholar 10Patzig M, Forbrig R, Kupper C, et al. Diagnosis and follow-up evaluation of central nervous system vasculitis: an evaluation of vessel-wall MRI findings. J Neurol. 2022; 269(2): 982- 996. CrossrefPubMedWeb of Science®Google Scholar Volume28, Issue9September 2022Pages 1464-1468 FiguresReferencesRelatedInformation

Objective:To summarize the clinical and imaging features of 10 patients with genetically diagnosed neuronal intranuclear inclusion disease (NIID) to avoid clinical misdiagnosis and mismanagement of NIID.Methods:Ten patients with NIID, admitted to our hospital from January 2020 to March 2022, were chosen in our study. All patients were confirmed as having NIID by NOTCH2NLC gene assay. Their clinical data, gene detection results and skin pathological results were collected and anlyzed. Results:These patients aged from 57 to 84 years, including 8 females. The episodic symptoms as main symptoms were noted in 6 patients, including 3 patients with encephalopathy, 1 patient with TGA, 1 patient with stroke-like episode, and 1 patient with migraine-like symptoms. Chronic progressive symptoms as main symptoms were noted in 4 patients, including 3 patients with dementia and 1 patient with Parkinson's disease. There were characteristic linear hyper-intensities in diffusion weighted imaging (DWI) in the corticomedullary junction predominantly in the frontal lobes. White matter lesions appeared in T2 Flair might have been noted years before lesions appeared in DWI, with wider ranges. All had GGC repeated expansion in NOTCH2NLC gene in non-coding area, with mutation number>60. Skin biopsy was performed in 6 patients, showing the formation of intranuclear inclusion bodies in different cells; and ubiquitin and P62 were found positive in immunohistochemical staining. Conclusions:NIID patients have large clinical heterogeneity; most patients have episodic symptoms as main manifestations, often accompanied by chronic progressive symptoms; stroke attack and migraine are rare clinical phenotypes of NIID. The high signal at the cortical medullary junction in DWI is a characteristic imaging change.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a subtype of CAA with an inflammatory response to the vascular β-amyloid deposits. Reliable and non-invasive clinical diagnostic methods may allow patients to avoid the side effects of brain biopsy. In this observational study, we retrospectively analyzed the clinical, laboratory, radiological features, treatment, and outcome of patients diagnosed with CAA-ri. The main purpose is to enhance knowledge of CAA-ri and to avoid misdiagnosis. We described 15 consecutive patients with probable or possible CAA-ri at Henan Provincial People’s Hospital according to a validation study of proposed criteria for the diagnosis of CAA-ri. The clinical features, imaging, laboratory findings, and treatment which included the response to immunotherapy were revealed in the study. The median age of 15 patients was 67.0 years (range 48.0–90.0 years), and the male-to-female ratio was 7: 8. In our study, the most common clinical manifestations were cognitive decline (7/15, 46.7

目的 探讨脑小血管病(cerebral small vessel disease,CSVD)患者胼胝体体积变化及其影响因素,分析CSVD患者胼胝体体积与运动功能的关系.方法 CSVD患者155例为CSVD组,同期头颅MRI正常或仅有轻微病变者161例为对照组.2组均行头颅MRI检查,图像经后处理得到胼胝体指数(corpus callosum index,CCD,比较2组既往病史、CCI等,记录CSVD患者CSVD影像学总负荷评分,应用步态分析仪记录CSVD患者步速、3 m步行时间及起坐时间.根据Fugl-Meyer量表评分将CSVD患者分为运动障碍组94例和无运动障碍组61例,比较2组CCI;采用多元线性回归分析CSVD患者CCI的影响因素;采用多因素logistic回归分析CSVD患者发生运动障碍的影响因素;采用偏相关分析CSVD患者CCI与运动功能的相关性.结果 采用1∶1倾向性评分匹配,成功匹配CSVD组和对照组各105例,匹配后CSVD组CCI(0.34±0.06)低于对照组(0.37±0.05)(t=-2.701,P=0.007),年龄及男性、吸烟、饮酒、高血压、糖尿病、高脂血症比率与对照组比较差异均无统计学意义(P＞0.05).155例CSVD患者CSVD影像学总负荷评分为(3.00±1.15)分,步速为(0.61±0.17)m/s,3 m步行时间为(5.33±1.73)s,起坐时间为(3.37±1.33)s.运动障碍组CCI(0.32±0.06)低于无运动障碍组(0.37±0.06)(t=5.227,P＜0.001).年龄(β=-0.002,95％CI:-0.003～-0.001,P＜0.001)、CSVD 影像学总负荷评分(β=-0.020,95％CI:-0.028～-0.012,P＜0.001)是CSVD患者CCI的影响因素;CCI(OR=0.062,95％CI:0.013～0.292,P＜0.001)是CSVD患者发生运动障碍的独立影响因素.CSVD患者CCI与步速呈正相关(r=0.395,P=0.001),与3 m步行时间呈负相关(r=-0.449,P＜0.001),与起坐时间无线性相关性(r=-0.186,P=0.128).结论 CSVD患者CCI降低,高龄、CSVD影像学总负荷评分增高的CSVD患者CCI降低更明显,提示胼胝体体积缩小;CCI是CSVD患者发生运动障碍的独立影响因素.

Background/Objective: AD-associated PSEN1 mutations exhibit high clinical heterogeneity. The discovery of these mutations and the analysis of their associations with cases such as EOAD should be critical to understanding AD's pathogenesis. Methods: We performed clinical analysis, neuroimaging, target region capture and high-throughput sequencing, and Sanger sequencing in a family of 3 generations. The underlying Alzheimer’s pathology was evaluated using biomarker evidence obtained from cerebrospinal fluid (CSF) amyloid testing and 18F-florbetapir (AV-45) PET imaging. Results: Target region capture sequencing revealed a novel heterozygous C to T missense point mutation at the base position 284 (c.850 C>T) located in exon 8 of the PSEN1 gene, resulting in a Proline-to-Serine substitution (P284S) at codon position 850. The mutation was also identified by Sanger sequencing in 2 family members, including proband and her daughter and was absent in the other 4 unaffected family members and 50 control subjects. Cerebrospinal fluid (CSF) amyloid test exhibited biomarker evidence of underlying Alzheimer’s pathology. 18F-florbetapir (AV-45) PET imaging indicated extensive cerebral cortex and cerebellar Aβ deposition. Conclusions: We discovered a novel PSEN1 pathogenic mutation, P284S, observed for the first time in a Chinese family with early-onset AD.

The purpose of this study was to identify the prevalence of severe headache or migraine and the association between dietary thiamine and riboflavin intake with headache history using a large, nationally representative population sample.

目的 分析伴中枢神经系统影像异常的急性间歇性卟啉病(AIP)患者的临床及影像特点,为临床诊疗提供更多依据.方法 回顾分析1995—2021年中国报道的38例头颅磁共振成像有异常病变的AIP患者的病历资料.结果 38例患者多为年轻女性,一般临床表现有腹痛、呕吐等.中枢神经系统损伤主要表现为痫性发作、意识障碍等.脑电图显示慢波或正常,脑脊液蛋白定量升高或正常.头颅磁共振成像表现为双侧皮层及皮层下病变,多为可逆性,也可表现为双侧深部灰质核团病变,此外有胼胝体压部病变等.其他实验室检查有尿胆原检测阳性、肝功能异常、低钠血症、贫血等.治疗方法包括去除诱因,急性发作期给予血红素、高糖及对症治疗,多数患者症状可明显改善.结论 伴中枢神经系统影像异常的AIP患者以年轻女性居多,腹痛常为首发症状.头颅磁共振成像可表现为皮层及皮层下白质病变或者深部灰质核团病变,也可累及胼胝体等其他部位.应结合病史和其他辅助检查,尽早识别及治疗.

Background: Sufficient understanding of the systemic inflammatory response after stroke will make the therapeutic strategy targeting inflammation more feasible. Here, we aimed to identify the globally alterations of circulating cytokines in super-acute ischemic stroke (AIS). Methods: A broad panel of 65 cytokines was measured in the plasma of twenty-eight AIS patients within 6 hours after stroke onset ( n =28), cerebral hemorrhagic patients ( n =28) and healthy controls ( n =18). The diagnostic power of the candidate cytokines and their relationship with the number of lymphocytes and neutrophils were analyzed by receiver operating characteristic (ROC) and spearman rank correlation respectively. Results: The expression level of plasma IL-1beta, IL-2, IL-2R, IL-5, IL-10, CD40L, HGF, MIP-3alpha and MMP-1 were obviously up-regulated, while IL-16 was down-regulated in AIS patients compared to healthy controls. Among them, IL-2R, IL-10, IL-16, MIP-3alpha, and MMP-1 were specially altered in AIS patients, while IL-1beta, IL-2, IL-5, CD40L and HGF were elevated simultaneously in AIS patients and hemorrhagic stroke patients. Interestingly, IL-6 and TNF-beta were found to be key cytokines among the 65 inflammatory factors to distinguish cerebral hemorrhage from ischemia. Furthermore, plasma IL-1beta, IL-16, CD40L and HGF were obviously correlated with the number of lymphocytes, and IL-1beta and IL-16 were significantly associated with the number of neutrophils in AIS patients. These results suggest that lymphocytes and neutrophils associated inflammation may play a pivotal role in AIS. Conclusions: These significantly changed inflammatory mediators could serve as biomarkers for AIS diagnosis. More importantly, except for some mutual pathological processes, AIS and hemorrhage had their own distinctive pathogenesis, and transformation of this knowledge to further research may provide novel treatment strategy for AIS.

目的 分析急性播散性脑脊髓炎合并多发性神经病的临床特点,以提高临床医生对本病的认识和诊疗水平.方法 对2017-12—2019-04就诊于河南省人民医院的8例急性播散性脑脊髓炎合并多发性神经病患者的临床表现、影像学、神经电生理、脑脊液特点及全身免疫相关指标进行回顾性分析.结果 本组8例患者为急性或亚急性起病,起病前多有前驱感染史.首先表现为中枢神经系统受累,其中7例影像学证实脑和(或)脊髓白质受累,1例脑电图证实中枢神经系统受损;迟缓性瘫痪、腱反射减弱或消失等周围神经受损的证据也随后出现,而后肌电图证实多发性神经根受损或神经源性损害.脑脊液检查细胞轻度升高或正常,蛋白升高或正常,只有1例见脑脊液细胞-蛋白分离.治疗上急性期激素冲击或免疫球蛋白治疗,症状和体征明显改善,缓解期辅以免疫抑制剂,随访无复发.结论 中枢神经系统和周围神经系统同时或相继出现脱髓鞘性改变,可能是一种不同于单纯中枢神经系统脱髓鞘和周围神经系统脱髓鞘的新疾病体,也可能是一种新的叠加综合征.