Xinghu Zhang

Objective Conventional imaging often struggles to differentiate between primary angiitis of the central nervous system (PACNS) and intracranial tumors. This study aims to evaluate the application value of proton magnetic resonance spectroscopy (¹H-MRS) in distinguishing PACNS from intracranial tumors. Methods This study collected data from 10 patients with PACNS and 15 patients with intracranial tumors (10 gliomas and 5 lymphomas) confirmed by pathological biopsy. The levels of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) in the lesion areas and contralateral normal brain tissue were measured and analyzed using ¹H-MRS, and the ratios of Cho/Cr, NAA/Cr, and Cho/NAA were calculated. The diagnostic efficacy of ¹H-MRS in distinguishing PACNS from intracranial tumors was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). Results Compared to contralateral normal brain tissue, significant differences were observed in the ratios of Cho/Cr, NAA/Cr, and Cho/NAA between the lesion areas of PACNS and intracranial tumors (P < 0.001). After correcting for the corresponding normal brain tissue spectra, the NAA/Cr ratio in PACNS lesion areas was significantly higher than in intracranial tumor lesions (0.90 vs. 0.25, P < 0.001), and the Cho/NAA ratio was significantly lower in PACNS lesions (1.98 vs. 9.00, P < 0.001), while the difference in Cho/Cr was not significant (1.59 vs. 1.94, P = 0.405). When the corrected NAA/Cr ratio was ≥ 0.71, the ROC-AUC for diagnosing PACNS was 1.00, with both specificity and sensitivity at 100%. The subgroup analysis of glioma/lymphoma yielded similar results. Conclusion The ratios of NAA/Cr and NAA/Cho are significantly meaningful in differentiating PACNS from intracranial tumors, and ¹H-MRS can be an effective tool for distinguishing these two conditions.

Purpose: Metabolic characterization of primary angiitis of the central nervous system (PACNS) is crucial for understanding the disease pathogenesis and progression mechanisms, but it has not been reported in patients. This study aimed to explore changes in the plasma metabolome during the active and remission phases of PACNS and identify potential biomarkers. Methods: We collected plasma samples from 35 patients with PACNS during the active and remission phases and 22 samples from patients with non-inflammatory disease as controls. Liquid and gas chromatography-mass spectrometry were used to analyze 63 plasma samples from 57 patients metabolically. Meanwhile, we cross-validated the metabolomics results with brain tissue transcriptomic data from comprehensive gene expression databases, enhancing the reliability of our conclusions. Results: A total of 3,233 metabolites were identified. Enrichment analysis showed significant changes in lactate/amino acid/glycerol–pyruvic–tricarboxylic acid, glycerophospholipid/sphingolipid-membrane metabolism, lysine/tryptophan-essential amino acid metabolism, and uracil metabolism pathways during the active phase of PACNS. These findings were confirmed in both the remission phase of PACNS patients and the transcriptomic samples. Meanwhile, metabolic abnormalities in patients with PACNS were observed with benzoxazole, sesquiterpenoid, and octyl-phenolic products, and enrichment of environmental pollutants and their estrogen-like effects. Twelve metabolites, including D-Ribose, 13s-HPODE, and C16 Sphinganine, showed potential diagnostic and therapeutic evaluation value. Conclusion: Our study identified potential biomarkers and metabolic characteristics of PACNS using integrated metabolomics and transcriptomics approaches. These findings highlight the importance of understanding PACNS from a metabolic perspective and guide future diagnostic and therapeutic strategies.

Background: Encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalanine-tyrosine metabolism and psychiatric symptoms remains unclear.Methods: We enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-α levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy.Results: In NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes.Conclusion: The serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker.

Objective: Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody‐positive NMOSD, but high‐quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control.Methods: Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded.Results: Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50–8.38 vs. 5.00–8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30–0.84 vs. 0.95–1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation.Discussion: After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile.

Purpose: Primary angiitis of the adult central nervous system (PACNS) is an increasingly recognized but limited disease. Using previous case reports, we sought to summarize the clinical symptoms, imaging manifestations, treatment, and prognosis of patients with biopsy-confirmed PACNS to guide clinical diagnosis and management. Methods: We searched the Web of Science database for studies published from January 2000 to April 2023, with the language set to English and the document type limited to [Article or Review or Letter or Editorial Material]. A systematic review of all case reports met the inclusion and exclusion criteria was performed. These patients’ clinical, pathological, and imaging characteristics were analyzed, and treatment and prognostic data were summarized. Results: We analyzed 69 articles, including 76 patients with biopsy-confirmed PACNS. And 57.9% of the patients were male, the median age at presentation was 47.0 years, and focal neurological deficits were the most common symptom in patients (78.9%), followed by headache (52.6%). The median duration of biopsy was 1.1 months, of which 49 (64.5%) patients were lymphocytic, 13 (17.1%) were granulomatous, 11 (14.5%) were amyloidotic, and 3 (3.9%) were necrotizing PACNS. Relapse events occurred in 41 (53.9%) patients, including 34 (44.2%) relapses and 8 (10.5%) deaths. Univariate logistic regression analysis revealed that symptomatic epilepsy, prolonged biopsy time window, and CD20 expression in pathological tissues might be independent risk factors for recurrent events in patients (HR=4.69, 95% CI: 1.51– 14.54, p=0.007; HR=1.11, 95% CI: 1.00– 1.22, p=0.043; HR=5.33, 95% CI: 1.07– 26.61, p=0.041). Conclusion: Adult PACNS is associated with frequent relapses and high mortality. Symptomatic epilepsy, prolonged biopsy time window, and CD20 expression in pathological tissue may be associated with recurrent events.

Background: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known. Findings: In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = − 0.401, p = 0.031). Conclusion: Increased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.

Varicella-zoster virus (VZV) infection may cause vascular inflammatory changes leading to an increased risk of stroke. Previous studies have focused on the risk of stroke and less on changes in stroke risk and prognosis. We aimed to explore the changing patterns of stroke risk and stroke prognosis after VZV infection. This study is a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies on stroke after VZV infection between January 1, 2000, and October 5, 2022. Relative risks were combined for the same study subgroups using a fixed-effects model and pooled across studies using a random-effects model. 27 studies met the requirements, including 17 herpes zoster (HZ) studies and ten chickenpox studies. There was an increased risk of stroke after HZ, and this risk decreased over time: relative risk 1.80 (95% CI 1.42–2.29) within 14 days, 1.61 (95% CI 1.43–1.81) within 30 days, 1.45 (95% CI 1.33–1.58) within 90 days, 1.32 (95% CI 1.25–1.39) within 180 days, 1.27 (95% CI 1.15–1.40) at one year and 1.19 (95% CI 0.90–1.59) after one year, with the same trend in the stroke subtype. The risk of stroke after herpes zoster ophthalmicus was higher, with a maximum relative risk of 2.26 (95% CI 1.35–3.78). The risk of stroke after HZ was higher in patients aged around 40 years: relative risk 2.53 (95% CI 1.59–4.02), and similar in men and women. Also, after pooling studies of post-chickenpox stroke, we found that the middle cerebral artery and its branches were most frequently involved (78.2%), with a better prognosis in most patients (83.1%) and less frequent vascular persistence progression (8.9%). In conclusion, the risk of stroke increases after VZV infection, decreasing over time. Post-infection vascular inflammatory changes often occur in the middle cerebral artery and its branches, with a better prognosis in most patients and less frequent persistent progression.