HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy.

Studies on myotonic dystrophy type 1 (DM1) have led to the RNA-mediated disease model for hereditary disorders caused by noncoding microsatellite expansions. This model proposes that DM1 disease manifestations are caused by a reversion to fetal RNA processing patterns in adult tissues due to the expression of toxic CUG RNA expansions (CUGexp) leading to decreased muscleblind-like, but increased CUGBP1/ETR3-like factor 1 (CELF1), alternative splicing activities. Here, we test this model in vivo, using the mouse HSALR poly(CUG) model for DM1 and recombinant adeno-associated virus (rAAV)-mediated transduction of specific splicing factors. Surprisingly, systemic overexpression of HNRNPA1, not previously linked to DM1, also shifted DM1-relevant splicing targets to fetal isoforms, resulting in more severe muscle weakness/myopathy as early as 4 to 6 wk posttransduction, whereas rAAV controls were unaffected. Overexpression of HNRNPA1 promotes fetal exon inclusion of representative DM1-relevant splicing targets in differentiated myoblasts, and HITS-CLIP of rAAV-mycHnrnpa1-injected muscle revealed direct interactions of HNRNPA1 with these targets in vivo. Similar to CELF1, HNRNPA1 protein levels decrease during postnatal development, but are elevated in both regenerating mouse muscle and DM1 skeletal muscle. Our studies suggest that CUGexp RNA triggers abnormal expression of multiple nuclear RNA binding proteins, including CELF1 and HNRNPA1, that antagonize MBNL activity to promote fetal splicing patterns.

D-dimers (DD) in CVST.

OBJECTIVE: We were interested in further confirming whether D-dimers (DD) are indeed elevated in cerebral venous sinus thrombosis (CVST) as reported in those studies. METHODS: CVST patients who had a plasma D-dimer test (139 cases) were included and divided into two groups: elevated D-dimer group (EDG) (>0.5 µg/mL; 65 cases) and normal D-dimer group (NDG) (≤0.5 µg/mL; 74 cases). The two groups were compared in terms of demographic data, clinical manifestation, laboratory and imaging data, using inferential statistical methods. RESULTS: The chi-squared and Fisher exact test showed that, compared to the NDG (74 cases), patients with elevated D-dimer levels were more likely to have a shorter symptom duration (SD) (30 ± 83.9 versus 90 ± 58.9 d, p = 0.003), more risk factors (75.4% versus 52.7%, p = 0.006), higher multiple venous sinus involvement (75.4% versus 59.5%, p = 0.037), increased fibrinogen (43.1% versus 18.9%, p = 0.037) and higher levels of blood glucose (18.3% versus 11%, p = 0.037). According to correlation analyses, D-dimer levels were positively correlated with number of venous sinuses involvement (NVS) (r = 0.321, p = 0.009) in the EDG. Multivariate logistic regression analysis showed that SD (OR, 0.025; 95% CI, 1.324-6.043; p = 0.000), NVS (OR, 1.573; 95% CI, 1.15-2.151; p = 0.005) and risk factors (OR, 3.321; 95% CI, 1.451-7.564; p = 0.004) were significantly different between the two groups. CONCLUSION: D-dimer is elevated in patients with acute/subacute CVST.

Incidence and risk factors of pleural effusions in patients with POEMS syndrome.

Information regarding the characteristics of pleural effusions in patients with POEMS syndrome is limited. The aim of this study was to describe the incidence and risk factors of pleural effusions in patients with POEMS syndrome and characterize the pleural fluid biochemistry in those patients. A retrospective review of 96 patients with POEMS syndrome was conducted. The patients were divided into groups with and without pleural effusions. The clinical data were obtained from medical charts. Risk factors were studied with univariate and multivariate analysis. The median age at the time of diagnosis of POEMS syndrome was 45.1 years, and the median disease duration was 30.4 months. Pleural effusions were detected in 41 (42.7%) of the 96 patients. Increased serum vascular endothelial growth factor (VEGF), complement component 3 (C3), Lambda light chain, tumour necrosis factor (TNF)-α, interleukin (IL)-6 levels and low albumin as well as cardiac disease were found to be significantly correlated with pleural effusions. By multivariate logistic regression, independent risk factors for pleural effusions in POEMS syndrome were VEGF [odds ratio (OR): 2.46, 95% confidence interval (CI): 1.720-3.414, p = 0.01], TNF-α (OR: 3.64, 95% CI: 1.073-4.338, p = 0.04) and C3 (OR: 3.77, 95% CI: 1.225-3.591, p = 0.02) levels. Pleural effusions are the most common thoracic involvement findings in patients with POEMS syndrome, and all the pleural fluids are exudates. Serum VEGF, TNF-α and C3 levels are identified as important risk factors for presence of pleural effusions in POEMS syndrome.

The characteristics of ascites in patients with POEMS syndrome.

The characteristics of ascites in patients with POEMS syndrome, which comprise polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes, are unknown. We described the frequency of ascites at presentation of POEMS syndrome and further evaluated for the pathogenesis and nature of the ascites. One hundred and six consecutive patients with POEMS syndrome in Chinese PLA General Hospital were evaluated for the presence of ascites, and the cellular and biochemical characteristics of the ascitic fluids were assessed. Serum levels of complement, cytokines, and clinical chemistry parameters were analyzed in peripheral blood samples of the patients with POEMS syndrome. Ascites was observed in 42 of 106 (39.6 %) patients with POEMS syndrome. Patients with ascites had significantly high serum levels of C3 and C4 complement components and TNF-α (all p < 0.01). In 31 (73.8 %) patients who underwent paracentesis, the ascitic fluids had low serum ascites albumin gradients (SAAG), indicating non-portal hypertension. Spontaneous bacterial peritonitis was not observed. Ascites is a common complication of POEMS syndrome and has characteristics of non-portal hypertension, based on low SAAG. Increased immune activation and inflammatory status could contribute to the pathogenesis of ascites in POEMS syndrome.

[MyoD mRNA expression in skeletal muscle of patients with myotonic dystrophy].

OBJECTIVE: To explore the mRNA expression of MyoD gene in the skeletal muscles of myotonic dystrophy (MD) patients. METHODS: Muscle biopsy specimens were obtained from the biceps muscles of arm of 4 MD patients and 4 healthy controls. Semi-quantitative reverse transcription polymerase chain reaction was performed to evaluate the mRNA expression of MyoD in the specimens. RESULTS: The mRNA expression index of MyoD of the MD patients was (0.267 +/- 0.114), significantly lower than that of the healthy controls [(0.788 +/- 0.136), P = 0.001]. CONCLUSION: Down-regulated mRNA expression of MyoD gene is involved in the mechanism of DM.

[The determination of medical reference values for tumor markers in cerebrospinal fluid].

OBJECTIVE: To determine medical reference values for tumor markers in cerebrospinal fluid. METHODS: Concentrations of CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP, NSE, SCC and HCG were determined by means of double-antibody sandwich ELISA in 110 patients excluding primary tumors and meningeal carcinomatosis using Roche E170 modular immunoassay analyzer. RESULTS: The determined medical reference values for tumor biomarkers in cerebrospinal fluid were as follows: CEA<0.573 microg/L, CA125<2.591 U/ml, CA15-3<2.045 U/ml, CA19-9<2.272 U/ml, CA72-4<1.252 U/ml, CYFRA21-1<1.44 ng/ml, AFP<0.968 microg/L, NSE<57.666 ng/ml, SCC<0.5 microg/L, HCG<0.769 U/L. There was no correlation between any tumor marker and age (P>0.05). Concentrations of tumor markers were not affected by gender (P>0.05). CONCLUSION: Medical reference values for CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP, NSE, SCC and HCG in cerebrospinal fluid were first determined.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease.

BACKGROUND: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations. METHODS: Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. RESULTS: Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests. CONCLUSIONS: The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.

A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient.

BACKGROUND: Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNAGlu) gene has previously been associated with maternally inherited diabetes and deafness. However, the association between MERRF and mitochondrial T14709C mutation (m.T14709C) has never been reported before. METHODS: Clinical information of a 17-year-old patient was collected; muscle biopsy and next-generation sequencing (NGS) of whole mitochondrial and neuromuscular disease panel were then conducted. Finally, sanger sequencing was carried out to confirm the mutations. RESULTS: The patient presented a typical MERRF phenotype with muscle weakness, epileptic seizure, clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial gene revealed m.T14709C mutation, confirmed by Sanger sequencing. CONCLUSION: We present a sporadic patient with typical MERRF presentation carrying the mutation of m.T14709C, which expanded the spectrum of m.T14709C.

[Investigating the diagnostic value of MHC-I expression in polymyositis].

OBJECTIVE: To investigate the diagnostic value of MHC-I expression in PM. METHODS: Analyzing the results of clinical and pathological findings and the immunohistochemical findings of MHC-I expression of 54 cases. RESULTS: Among the 16 patients with PM, 63 percent patients showed inflammatory infiltration, 94 percent showed MHC-I expression; Among 19 patients with progressive muscular dystrophy, 9 percent patients showed inflammatory infiltration, 11 percent showed MHC-I expression. The other 19 patients showed no inflammatory infiltration and MHC-I expression. CONCLUSION: MHC-I expression as a diagnostic index of PM was appropriate, which had ideal sensitivity, specificity and negative likelihood ratio.

A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb-girdle Muscle.

BACKGROUND: Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation (c.5302G>C) of AGRN in a Chinese CMS pedigree. METHODS: We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy (including 17 CMS genes). RESULTS: In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband's two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation (c.5302G>C, p. A1768P) of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. CONCLUSIONS: This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.

A novel thymidine phosphorylase mutation in a Chinese MNGIE patient.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with mitochondrial alterations. MNGIE is characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia, ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused by mutation of the TYMP gene. We studied the clinical and biochemical characteristics of a family with MNGIE. The proband was a 48-year-old male presenting with diarrhea and progressive weight loss. He also had ptosis and exhibited eyeball fixation. His blood and cerebrospinal fluid lactate levels were elevated. Magnetic resonance imaging of the brain revealed diffuse leukoencephalopathy. Ragged red fibers and cytochrome c oxidase-deficient fibers were apparent on muscle biopsy. His vision and ptosis deteriorated significantly during follow-up. Our clinical diagnosis of MNGIE was confirmed by TYMP gene analysis. We discovered a homozygous TYMP c.1193-1216 dup-GGGCGCTGCCGCTGGCGCTGGTGC mutation (a duplication). Some of the family members were heterozygous for the mutation but had no clinical features. We predicted the function of this mutation using PredictProtein and found that the secondary structure had changed in the region of the helix and strand, the transmembrane region, and the protein-protein binding sites. The family described herein exhibited biochemically, genetically, and functionally confirmed MNGIE syndrome.

Increased Expression of the NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome in Dermatomyositis and Polymyositis is a Potential Contributor to Their Pathogenesis.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations. Responding to a wide range of exogenous and endogenous microbial or sterile stimuli, NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1, which processes the pro-inflammatory cytokines pro-interleukin (IL)-1ß and pro-IL-18 into active and secreted IL-1ß and IL-18. The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases. However, it remains unclear whether it is involved in the pathogenesis of DM/PM, which we aim to address in our research. METHODS: In this study, 22 DM/PM patients and 24 controls were recruited. The protein and RNA expression of IL-1ß, IL-18, NLRP3, and caspase-1 in serum and muscle samples were tested and compared between the two groups. RESULTS: The serum IL-1ß and IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay (ELISA, DM vs. control, 25.02 ± 8.29 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001; PM vs. control, 26.49 ± 7.79 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001). Moreover, the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients exhibited higher RNA expression of IL-1ß, IL-18, and NLRP3 in the muscle (for IL-1ß, DM vs. control, P= 0.0012, PM vs. control, P= 0.0021; for IL-18, DM vs. control, P= 0.0045, PM vs. control, P= 0.0031; for NLRP3, DM vs. control, P= 0.0017, PM vs. control, P= 0.0006). Moreover, the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls. CONCLUSIONS: Our findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM/PM. High NLRP3 expression led to elevated levels of IL-1ß and IL-18 and could be one of the factors promoting disease progress.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles.

BACKGROUND: Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected. METHODS: A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out. RESULTS: Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found. CONCLUSIONS: We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.

[Regulatory T cells in the treatment of autoimmune myositis in mice: efficacy and mechanism].

OBJECTIVE: To investigate effect of CD4(+) CD25(+) Foxp3(+) Tregs in the treatment of autoimmune myositis (EAM) in mice and explore the possible mechanisms. METHODS: Mouse models of EAM were divided randomly into model group and treatment group, and the latter received infusion of CD4(+) CD25(+) Foxp3(+) Tregs separated from normal mouse spleen by magnetic activated cell sorting. The changes of muscle pathology was observed, and the expression of PD-1 and CTLA-4 in spleen CD4(+) CD25(+) Foxp3(+) Tregs was analyzed using flow cytometry; peripheral blood IL-10 and TGF-ß levels were tested using double antibody sandwich ELISA. RESULTS: Compare with the model group, the mice in the treatment group showed significantly reduced muscular inflammatory cell infiltration, increased blood levels of IL-10 and TGF-ß (P<0.05), and increased expression of PD-1 and CTLA-4 in spleen CD4(+) CD25(+) Foxp3(+) Tregs (P<0.05). CONCLUSION: CD4(+) CD25(+) Foxp3(+) Tregs reinfusion produces therapeutic effect in mice with EAM by increasing peripheral blood IL-10 and TGF-ß levels and PD-1 and CTLA-4 expressions in spleen CD4(+) CD25(+) Foxp3(+) Tregs.

Clinical and pathological features of patients with nemaline myopathy.

Nemaline myopathy (NM) is a rare congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. This study aimed to summarize and analyze retrospectively the clinicopathological features of 28 patients with NM. Among the 28 patients, 15 were classified as of the typical congenital type, manifested as lower- or four-limb weakness as the first symptom and slowly progressive course. Six patients were classified as of childhood onset type, with lower-limb weakness and progressive course. Seven patients were classified as of the adult onset type, with rapidly progressive course and obvious muscle atrophy. Patient's 1, 16 and 23 had rapid clinical progression. On follow up, the three patients showed respiratory failure. Limb weakness in all patients was proximal­dominant. Hypotonia was observed in most patients. High arched feet were also observed as dysmorfic features. In all patients, the creatine kinase (CK) level was normal or mildly elevated, and electromyography revealed myogenic changes. Nemaline bodies were observed under a light microscope in more than half of the patients' muscle fibers, and especially in type I fibers. All patients showed fiber type I predominance and atrophy. Modified Gömöri trichrome staining showed characteristic purple­colored rods. Muscle electron microscopy revealed the presence of high electron­dense nemaline bodies around the nucleus, and of a disorganized myofibrillar apparatus, with broken myofilaments and irregular myofibrils and Z lines. The 28 patients with NM shared a number of clinical features, such as proximal limb weakness, reduced deep tendon reflex and dysmorfic features. Differences were also observed between the three types of patients, with regards to course progression, disease severity and respiratory failure. In conclusion, patients with NM showed great clinical heterogeneity. The diagnosis of NM was mainly based on the muscle biopsy.

Complement membrane attack complex is related with immune-mediated necrotizing myopathy.

This study is to investigate the expression of complement membrane attack complex (C5b-9) in the skeletal muscle of patients with necrotizing myopathy (NM), and to investigate the relationship between C5b-9 and NM. Thirteen patients with NM and control patients with polymyositis and muscular dystrophy were enrolled in this study. Examinations including creatine kinase (CK) and L-lactate dehydrogenase (LDH) in the serum, electromyogram and muscle pathological examination were performed. C5b-9 expression in the skeletal muscle was determined by immunohistochemistry and analyzed by Image Plus Pro 6.0. C5b-9 expression was particularly prominent in necrotic muscle fibers, and also positive in blood vessels. C5b-9 diffusely expressed in vascular endothelial cells and smooth muscle layer. But the intensity was not related with the elevated level of serum CK. So, C5b-9 is strongly expressed in the necrotic muscle fiber and blood vessels, and may contribute to the pathogenesis of NM.

Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57). Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11), and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%). The sensitivity of EEG was 79.6% (43/54). For DWI and PET examinations, the sensitivities were 94% (47/50) and 94.1% (16/17), respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the diagnosis of sCJD.

Dural enhancement detected by magnetic resonance imaging reflecting the underlying causes of cerebral venous sinus thrombosis.

Dural enhancement detected by magnetic resonance imaging is a common finding in patients with cerebral venous sinus thrombosis (CVST) and is usually interpreted as a change secondary to CVST. We report two cases of CVST with intense and diffuse dural enhancement that resulted from pachymeningitis in one patient and spontaneous intracranial hypotension in another. Pachymeningitis and spontaneous intracranial hypotension were also determined to be the underlying causes of CVST. The clinical data of these two patients are described. In patients with CVST, dural enhancement is not always a secondary change to CVST. It can be a manifestation of the underlying causes of CVST. When diffuse and intense dural enhancement is revealed, sufficient ancillary tests are warranted to rule out other potential pathological changes of the dura mater those can result in CVST.