Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound.

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

BAG3-Related Myofibrillar Myopathy Presenting as Hypercapnia: A Case Report and Literature Review.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide. The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia. Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation. Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation. The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3. Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date, including this patient and literature review. The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life. Most patients presented toe/clumsy walking or running as the onset symptom, followed by muscle weakness or atrophy. Creatine kinase levels were elevated in fourteen patients and were normal in three. Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment. Except for one not reported, heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation. Z-disk streaming and aggregation could be observed in most of the patients' muscle histology. In the long-term follow-up, five patients died of cardiac or respiratory failure. Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy. It should be considered as a rare differential diagnosis of hypercapnia.

[Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2].

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.

The effect of CCR5Δ32 on the risk of grade 3-4 acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.

OBJECTIVE: Many studies have showed that CCR5 was involved in the pathological process of acute graft-versus-host disease (aGVHD). However, the relationship between CCR5Δ32, a frameshift mutation, and grade 3-4 acute GVHD risk has not been well established. We performed a meta-analysis to explore the effects of CCR5 gene polymorphisms on grade 3-4 aGVHD. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched to collect relevant articles. Studies about association between CCR5 genotype in recipients or donors of allo-HSCT and aGVHD risk were included. All pooled analyses were based on fixed effects models. The effects were assessed from odd ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of three studies comprising 937 recipients and 914 donors of allo-HSCT met the inclusion criteria. Compared with the wild-type CCR5 homozygotes, the pooled odd ratios (ORs) for CCR5Δ32 mutation (both homozygous and heterozygous) was 0.71 (95% CI, 0.40-1.26; P = .24) for donors, and 0.79 (95% CI, 0.35-1.81; P = .58) for recipients. No relationship was found between the presence of the CCR5Δ32 mutation and grade 3-4 aGVHD. Larger clinical investigations and retrospective studies are needed to explore the association of CCR5 gene polymorphisms with aGVHD risk as well as the outcome of HSCT.

Intracranial atherosclerosis in Chinese young adult stroke patients.

BACKGROUND: Until now, intracranial atherosclerosis has been less well studied because of its rarity. We sought to investigate the prevalence and risk factors of intracranial atherosclerosis in Chinese young adult stroke patients. METHODS: We retrospectively reviewed the medical records of consecutive young adult patients with first-ever ischemic stroke at our institution from May 2007 to May 2012. The demographic features and risk factors of intracranial large-artery atherosclerotic (LAA) stroke were analyzed by comparison with other stroke subtypes. RESULTS: One hundred ninety-seven patients (age 39±9 years, 127 male) were recruited. There were 81 (41%) patients with LAA stroke, including 68 (35%) strokes because of intracranial stenosis. Male gender (P=.001), dyslipidemia (P=.015), smoking (P<.001), hypertension (P<.001), hyperhomocysteinemia (P=.003), and family history of stroke (P=.024) were more common in patients with intracranial LAA stroke than with non-LAA stroke. A high percentage of patients with intracranial LAA stroke had multiple modifiable risk factors (ie, at least 2 of dyslipidemia, hypertension, diabetes mellitus, smoking, and hyperhomocysteinemia), much more than the patients with non-LAA stroke (82% versus 42%, P<.001). Simultaneous multiple modifiable risk factor exposure was the strongest "risk factor" for intracranial LAA stroke, with the adjusted odds ratio of 4.99. CONCLUSIONS: Intracranial atherosclerosis is highly prevalent in Chinese young stroke patients. Our results suggest that simultaneous exposure to multiple risk factors may contribute to the early development of intracranial atherosclerosis.

Causes and outcomes of persistent vegetative state in a Chinese versus American referral hospital.

OBJECTIVE: To compare the etiologies and clinical outcomes of patients in a persistent vegetative state (PVS) between a Chinese and US referral hospital. METHODS: A retrospective, observational study at the Peking Union Medical College Hospital, Beijing, China and Johns Hopkins Hospital, Baltimore, USA (2001-2010) was performed. RESULTS: There were 36 cases of PVS diagnosed. In Beijing, there were 19 cases: mean age 57 years, range 3-86, (42 %) female, with 37 % of patients observed to survive more than 1 year (range >1 month to >28 years, median >6 months). Causes of PVS in Beijing were hemorrhagic stroke (n = 4, 21 %), ischemic stroke (n = 2, 11 %), cardiac arrest (n = 5, 26 %, including 4 with attempted cardiopulmonary resuscitation (CPR)), traumatic brain injury (n = 3, 16 %), and one each of mitochondrial encephalomyopathy, acute disseminated encephalomyelitis, Lennox Gastaut Syndrome, and epilepsy with craniopharyngioma (n = 4, 21 %). In Baltimore, there were 17 cases of PVS: mean age 43 years, range 15-83, 59 % female, with 41 % observed to survive more than 1 year (range >1 month to >10 years, median >3 years). Causes of PVS in Baltimore were ischemic stroke (n = 3, 18 %), cardiac arrest (n = 3, 18 %, including one with attempted CPR), traumatic brain injury (n = 3, 18 %), neurodegenerative conditions (n = 2, 12 %), and hypoxic ischemic encephalopathy due to respiratory arrest (n = 3, 18 %), metabolic derangements (n = 2, 12 %), and meningitis (n = 1, 6 %). CONCLUSIONS: There may be a long survival period for patients with PVS, including in China where resource constraints exist for acute neurologic care. Stroke appears to be the most common underlying cause of PVS in Chinese patients, followed closely by cardiac arrest with attempted CPR. There appear to be more varied causes of PVS in the US referral hospital with a predominance of stroke, cardiac arrest, and traumatic brain injury.

Circulating mitochondrial DNA is associated with anemia in newly diagnosed hematologic malignancies.

Recent reports discovered that red blood cells (RBCs) could scavenge cell-free mitochondrial DNA (mtDNA), which drives the accelerated erythrophagocytosis and innate immune activation characterized by anemia and inflammatory cytokine production. However, the clinical value of the circulating mtDNA copy number alterations in hematologic malignancies is poorly understood. Our data showed that in comparison to healthy group, the patients group had significantly higher mtDNA and histone H4 levels. Moreover, we observed that RBC-bound mtDNA and histone H4 were negatively correlated with hemoglobin in patients. In addition, cytokines and chemokines levels in patients differed significantly from normal controls (21 higher, 7 lower). Our study suggested that both circulating mtDNA and histone H4 were associated with anemia in hematologic malignancies, which helps to further understand the potential mechanism of anemia development in patients with hematologic malignancies. This information may play a vital role in the specific therapeutic interventions for leukemia in the future.

Changes in patient peripheral blood cell microRNAs after total body irradiation during hematopoietic stem cell transplantation.

Background: Ionizing radiation exposure is a great threat to human health. MicroRNAs (miRNAs) have been shown to play an important role in radiation-induced biological effects. Here, we investigated plasma miRNA expression changes and differentially expressed miRNAs in radiotherapy patients exposed to cobalt-60 (60Co) gamma rays to provide an experimental basis for human plasma miRNAs as an estimation indicator for ionizing radiation injury. Methods: Six patients with acute lymphoblastic leukemia (ALL) received continuous 5 gray (Gy) total body irradiation (TBI) twice. At 12 hours after irradiation, miRNA microarray was applied to screen for differentially expressed miRNAs, with some miRNAs confirmed by real-time polymerase chain reaction (RT-PCR) assay. Bioinformatic analysis was carried out to identify the relevant target genes and biological function of the differentially expressed miRNAs. Results: After radiotherapy patients were exposed to 5 Gy gamma radiation, the expression of 9 plasma miRNAs was significantly upregulated, and the expression of 2 miRNAs was downregulated. After irradiation with 10 Gy gamma radiation, the blood plasma of radiotherapy patients contained 18 differentially expressed miRNAs, of which 17 were upregulated and 1 was downregulated (P<0.05). The expression of miR-4532, miR-4634, miR-4655-5p, miR-4763-3p, miR-4785, miR-6087, miR-6850-5p, and miR-6869-5p were significantly upregulated in both the 5-Gy and 10-Gy dose groups, showing a certain dose-response relationship. The RT-PCR results were consistent with the findings of high-throughput sequencing. In addition, the target genes of the differentially expressed miRNAs were mainly involved in RNA transcription and DNA damage. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these miRNAs participated in phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Ras, mitogen-activated protein kinase (MAPK), and other signaling pathways. Conclusions: The expression of differential plasma miRNAs of radiotherapy patients was associated with irradiation injury and showed a certain dose-effect relationship. These differentially coexpressed plasma miRNAs could be used as an early indicator for estimating radiation injury.

Are Anti-Inflammatory Cytokines Associated with Cognitive Impairment in Patients with Insomnia Comorbid with Depression? A Pilot Study.

BACKGROUND: To distinguish insomnia comorbid with depression (ICD) from chronic insomnia disorder (CID) by exploring the relationship between serum levels of frequently overlooked anti-inflammatory cytokines and cognitive function. METHODS: A total of 42 ICD patients, 63 CID patients, and 42 healthy control subjects were enrolled in the study. The Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale were used to assess sleep quality and depression severity, respectively. The Chinese-Beijing version of Montreal Cognitive Assessment scale (MoCA-C) and Nine-Box Maze Test (NBMT) were used to assess cognitive function. Serum levels of anti-inflammatory interleukins (IL-1RA, IL-4, IL-5, IL-10, IL-13, and IL-28A), transforming growth factor (TGF)-ß1, granulocyte-macrophage colony-stimulating factor, interferon-γ, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES) were measured by enzyme-linked immunosorbent assay. RESULTS: The ICD group had significantly more errors in the spatial reference task (H=2.55, Ps=0.03) and spatial working memory task (H=5.67, Ps<0.01) of the NBMT, as well as lower levels of IL-1RA (H=-2.85, Ps=0.01), IL-4 (H=-3.28, Ps<0.01), IL-5 (H=-3.35, Ps<0.01), IL-10 (H=-4.46, Ps<0.01), and IL-28A (H=-2.75, Ps=0.02) than control subjects. Compared with the CID group, the ICD group had significantly more errors in the spatial reference memory task (H=-2.84, Ps=0.01) of the NBMT, and lower levels of IL-5 (H=3.41, Ps<0.01), IL-10 (H=5.30, Ps<0.01), IL-13 (H=3.89, Ps<0.01), and GM-CSF (H=2.72, Ps=0.02). A partial correlation analysis showed that the level of one or more of IL-4, IL-5, IL-10, IL-13, and TGF-ß1 was positively correlated with cognitive function (MoCA-C score and/or performance in spatial memory task) in ICD patients. CONCLUSION: ICD is a distinct condition that can be distinguished from CID based on immune dysfunction and specific types of cognitive dysfunction.

Relationships Between a Range of Inflammatory Biomarkers and Subjective Sleep Quality in Chronic Insomnia Patients: A Clinical Study.

PURPOSE: To examine whether associations exist between chronic insomnia disorder (CID) and overlooked inflammatory factors (Serum amyloid protein A [SAA]), tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], and regulated on activation and normal T cell expressed and presumably secreted [RANTES]). PATIENTS AND METHODS: A total of 65 CID patients and 39 sex- and age-matched good sleeper (GS) controls participated in this study. They completed a baseline survey to collect data on demographics, and were elevated sleep and mood by Pittsburgh Sleep Quality Index (PSQI), Athens Insomnia Scale (AIS), 17-item Hamilton Depression Rating Scale (HAMD-17) and 14-item Hamilton Anxiety Rating Scale (HAMA-14), respectively. The blood samples were collected and tested the serum levels of SAA, TNF-α, GM-CSF and RANTES. RESULTS: The CID group had higher serum levels of SAA, TNF-α, and GM-CSF and a lower level of RANTES than the GS group. In the Spearman correlation analysis, SAA and GM-CSF positively correlated with the PSQI and AIS scores. After controlling for sex, HAMD-17 score, and HAMA-14 score, the partial correlation analysis showed that GM-CSF was positively correlated with PSQI score. Further stepwise linear regression analyses showed that GM-CSF was positively associated with the PSQI and AIS scores, while RANTES was negatively associated with them, and SAA was positively associated with just the AIS score. CONCLUSION: The serum levels of inflammatory mediators (SAA, TNF-α, and GM-CSF) were significantly elevated and the level of RANTES was significantly decreased in CID patients and, to some extent, the changes are related to the severity of insomnia. These findings may help us to improve interventions to prevent the biological consequences of CID by inhibiting inflammation, thereby promoting health.

Alteration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation.

AIM: To investigate the association between the configurational and compositional changes of nuclear matrix and the differentiation of carcinoma cells. METHODS: Cells cultured with or without 5 x 10(-3) mmol/L of hexamethylene bisacetamide (HMBA) on Nickel grids were treated by selective extraction and prepared for whole mount observation under electron microscopy. The samples were examined under transmission electron microscope. Nuclear matrix proteins were selectively extracted and subjected to subcellular proteomics study. The protein expression patterns were analyzed by PDQuest software. Spots of differentially expressed nuclear matrix proteins were excised and subjected to in situ digestion with trypsin. The peptides were analyzed by matrix-assisted laser-desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Data were submitted for database searching using Mascot tool (www.matrixscience.com). RESULTS: The nuclear matrix (NM) and intermediate filament (IF) in SMMC-7721 hepatocarcinoma cells were found relatively sparse and arranged irregularly. The nuclear lamina was non-uniform, and two kinds of filaments were not tightly connected. After induction for differentiation by HMBA, the NM-IF filaments were concentrated and distributed uniformly. The heterogeneous population of filaments, including highly branched ultrathin filaments could also be seen in the regular meshwork. The connection between the two kinds of filaments and the relatively thin, condensed and sharply demarcated lamina composed of intermediate-sized filaments was relatively fastened. Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pyst1, hypothetical protein, nucleophosmin 1, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit, beta-tubulin, and SIN3B were upregulated with the last one, SR2/ASF found only in the differentiated SMMC-7721 cells. CONCLUSION: The induced differentiation of SMMC-7721 cells by HMBA is accompanied by the configurational changes of nuclear matrix-intermediate filament (NM-IF) system and the compositional changes of nuclear matrix protein expression. These changes may be important morphological or functional indications of the cancer cell reversion.

Contribution and underlying mechanisms of CXCR4 overexpression in patients with systemic lupus erythematosus.

Aberrant expression of CXCR4 has been indicated to play a role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanism of CXCR4 dysregulation in SLE is unclear. This study is aimed to explore the clinical significance and possible mechanisms of abnormal CXCR4 expression on B cells from patients with untreated SLE. Expression of CXCR4 on peripheral B cells was determined by flow cytometry and western blotting. Freshly isolated B cells were cultured with exogenous interleukin 21(IL-21) in the presence or absence of CD40 ligand (CD40L) plus anti-IgM antibody (aIgM), and changes in CXCR4 expression were detected. Involvement of phosphatidylinositol 3 kinase (PI3K)/Akt and Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathways was assessed by adding blocking agents Ly294002 and AG490. Since CD63 is reported to mediate endosomal recruitment of CXCR4 and BCL6 is capable of silencing CD63 gene transcription, we also measured BCL6 and CD63 gene transcription with real-time PCR. It was shown that CXCR4 expression on B cells was significantly upregulated in SLE patients, especially in those with lupus nephritis, and was positively correlated with SLE Disease Activity Index scores and negatively with the serum complement 3 levels (P<0.05). Downregulation of CXCR4 by IL-21 was intact. In contrast, a similar effect of aIgM plus CD40L in downregulating CXCR4 expression was defective in SLE patients but was restored by co-stimulation with IL-21 in vitro. Both Ly294002 and AG490 promoted downregulation of surface CXCR4 expression on B cells from SLE patients (P=0.078 and P=0.064). Furthermore, B cells from SLE patients exhibited diminished CD63 mRNA and enhanced BCL6 mRNA expression (both P<0.05). To sum up, CXCR4 was overexpressed on SLE B cells, positively correlating with disease activity and kidney involvement. Overactivation of the PI3K/Akt and JAK/STAT pathways as well as defective CD63 synthesis may contribute to CXCR4 dysregulation in SLE.

Changes of nuclear matrix proteins following the differentiation of human osteosarcoma MG-63 cells.

Human osteosarcoma MG-63 cells were induced into differentiation by 5 mmol/L hexamethylene bisacetamide (HMBA). Their nuclear matrix proteins (NMPs) were selectively extracted and subjected to two-dimensional gel electrophoresis analysis. The results of protein patterns were analyzed by Melanie software. The spots of differentially expressed NMPs were excised and subjected to in situ digestion with trypsin. The maps of peptide mass fingerprinting were obtained by MALDI-TOF-MS analysis, and were submitted for NCBI database searches by Mascot tool. There were twelve spots changed remarkably during the differentiation induced by HMBA, nine of which were identified. The roles of the regulated proteins during the MG-63 differentiation were analyzed. This study suggests that the induced differentiation of cancer cells is accompanied by the changes of NMPs, and confirms the presence of some specific NMPs related to the cancer cell proliferation and differentiation. The changed NMPs are potential markers for cancer diagnosis or targets for cancer therapy.

Quantitating Changes in Jitter and Spike Number Using Concentric Needle Electrodes in Amyotrophic Lateral Sclerosis Patients.

BACKGROUND: Single-fiber electromyography (SFEMG) has been suggested as a quantitative method for supporting chronic partial denervation in amyotrophic lateral sclerosis (ALS) by the revised EI Escorial criteria. Although concentric needle (CN) electrodes have been used to assess jitter in myasthenia gravis patients and healthy controls, there are few reports using CN electrodes to assess motor unit instability and denervation in neurogenic diseases. The aim of this study was to determine whether quantitative changes in jitter and spike number using CN electrodes could be used for ALS studies. METHODS: Twenty-seven healthy controls and 23 ALS patients were studied using both CN and single-fiber needle (SFN) electrodes on the extensor digitorum communis muscle with an SFEMG program. The SFN-jitter and SFN-fiber density data were measured using SFN electrodes. The CN-jitter and spike number were measured using CN electrodes. RESULTS: The mean CN-jitter was significantly increased in ALS patients (47.3 ± 17.0 µs) than in healthy controls (27.4 ± 3.3 µs) (P < 0.001). Besides, the mean spike number was significantly increased in ALS patients (2.5 ± 0.5) than in healthy controls (1.7 ± 0.3) (P < 0.001). The sensitivity and specificity in the diagnosis of ALS were 82.6% and 92.6% for CN-jitter (cut-off value: 32 µs), and 91.3% and 96.3% for the spike number (cut-off value: 2.0), respectively. There was no significant difference between the SFN-jitter and CN-jitter in ALS patients; meanwhile, there was no significant difference between the SFN-jitter and CN-jitter in healthy controls. CONCLUSION: CN-jitter and spike number could be used to quantitatively evaluate changes due to denervation-reinnervation in ALS.

Single-fiber Electromyography in the Extensor Digitorum Communis for the Predictive Prognosis of Ocular Myasthenia Gravis: A Retrospective Study of 102 Cases.

BACKGROUND: Single-fiber electromyography (SFEMG) abnormality in the extensor digitorum communis (EDC) was reported in ocular myasthenia gravis (OMG), which indicated subclinical involvement beyond extraocular muscles in OMG patients. The relationship between the abnormal findings of SFEMG in EDC and the probability for OMG to develop generalized myasthenia gravis (GMG) is unknown. This retrospective study aimed to determine the predictive value of abnormality of SFEMG in EDC of OMG patients. METHODS: One-hundred and two OMG patients underwent standard clinical diagnosis process and SFEMG test in EDC muscle when diagnosed and were clinically followed up for 5 years. The SFEMG data were compared between different clinical groups according to thymus status, onset age, and different outcome of OMG developing. Chances of progressing to GMG were compared between two different groups according to SFEMG and repetitive nerve stimulation (RNS) results, acetylcholine receptor antibody (AchRAb) titer, thymus status, and onset age. RESULTS: Abnormal SFEMG results were observed in 84 (82.4%) patients. The mean jitter, percentage of jitter >55 µs (%), and blocking were higher in OMG patients than in healthy volunteers. There were no statistical differences in jitter analysis between thymoma group and non-thymoma group (P = 0.65), or between the later OMG group and the later GMG group (P = 0.31), including mean jitter, percentage of jitter >55 µs (%), and blocking. Elderly group (≥45 years old) had a higher mean jitter than younger group (t = 2.235, P = 0.028). Total 55 OMG developed GMG, including 47 in abnormal SFEMG group while 8 in normal SFEMG group. There was no statistical difference in the conversion rates between the two groups (χ2 = 0.790, P = 0.140). RNS abnormality, AchRab titer, or onset age had no correlation with OMG prognosis (P = 0.150, 0.070, 0.120, respectively) while thymoma did (χ2 = 0.510, P = 0.020). CONCLUSION: SFEMG test in the EDC showed high abnormality in OMG, suggesting subclinical involvement other than extraocular muscles. Nevertheless, the abnormal jitter analysis did not predict the prognosis of OMG according to clinical follow-up.

Low awareness of stroke guidelines and preference for Chinese herbs in community physicians: a national survey in China.

BACKGROUND: Physicians' adherence to stroke guidelines is becoming a critical part of public stroke care system. The objective of this national survey was to examine Chinese physicians' awareness of the guidelines in secondary stroke prevention. METHODS: This is a non-commercial and no-incentive internet survey. Respondents were asked to perform a self-examination of 13 questions regarding their stroke practice. Their awareness of stroke guidelines, preference for Chinese traditional herbs (CTH), and patients' expense for stroke treatment were surveyed and compared between physicians from community and from tertiary hospitals using univariate analysis and logistic regression. RESULTS: A total of 8,581 physicians (70.1% from community hospitals) responded to the survey. Only 32.1% physicians considered risk factors control necessary for stroke. For the treatments of symptomatic carotid stenosis, only 10.4% physicians selected carotid endarterectomy and anti-platelet plus controlling stroke risk factors. Only 21.45% physicians selected warfarin anticoagulation for stroke patients with atrial fibrillation. In contrast, a high percentage (64.56%) of physicians had positive attitude towards CTH. Compared with those from tertiary hospitals, community physicians were more likely unaware of the guidelines and preferred CTH. Those who prescribed CTH reported more patients' cost (P<0.001, OR 1.78, 95% CI, 1.55-2.04) than who didn't. CONCLUSIONS: There is a very low awareness of stroke guidelines in Chinese community physicians. A well-organized continuing stroke-guidelines education should be an essential part of public stroke-care system in China. Also, more well-designed clinical trials are required to establish the safety and effectiveness of CTH.

Luminal thrombosis in middle cerebral artery occlusions: a high-resolution MRI study.

BACKGROUND AND PURPOSE: High signals within occluded vessels on T1-weighted fat-suppressed images (HST1) are highly suggestive of luminal thrombosis. We sought to investigate the feasibility of in vivo identification of luminal thrombosis in middle cerebral artery (MCA) occlusions using high-resolution magnetic resonance imaging (HR-MRI). METHODS: We retrospectively reviewed the HR-MRI data of 25 patients with unilateral symptomatic MCA occlusion. HST1 were defined as an area of high signal within the cross-section of occluded MCA, the intensity of which was >150% of the signal of adjacent muscles. The prevalence of HST1 and their relationship to infarct sizes and infarct patterns were analyzed. RESULTS: The average time from stroke onset to HR-MRI examination was 9±6 days. There were 18 (72%) occluded vessels with HST1 on HR-MRI. HST1 were observed in 5/7 patients with a large territory infarct (≥1/3 MCA distribution) and 13/18 patients without (P=0.37). In the patients with non-large territory infarcts, the presence of HST1 was similar in those with and without border zone infarcts (9/13 vs. 4/5, P=0.42). CONCLUSIONS: It's feasible to in vivo identify luminal thrombosis in occluded MCA. HR-MRI is a potentially powerful tool for investigating the mechanisms of stroke due to MCA occlusions.

Deep tiny flow voids along middle cerebral artery atherosclerotic occlusions: a high-resolution MR imaging study.

BACKGROUND AND PURPOSE: We aim to report the "deep tiny flow voids" (DTFV), a unique HR-MRI finding suggestive of deep collateral vessels along middle cerebral artery (MCA) occlusions. METHODS: We retrospectively reviewed the HR-MRI data of 60 patients with unilateral MCA occlusion (32 symptomatic and 28 asymptomatic) and 205 control subjects with normal MCA on magnetic resonance angiography. The presence or absence of DTFV, defined as three or more flow voids along the occluded MCA on at least two consecutive T2-weighted image slices, was observed. The relationships among DTFV, clinical presentations, and infarct sizes were analyzed. RESULTS: DTFV were identified in 20/28 (71%) patients with asymptomatic MCA occlusions, much more frequently than in the patients with symptomatic occlusions (5/32, 16%) (P<0.001). There were 9 patients with a large territorial infarction (≥ 1/3 MCA distribution), none of whom had DTFV on HR-MRI. DTFV was not observed in any control subject. CONCLUSIONS: DTFV are pathological conditions and associated with relatively good imaging outcomes and asymptomatic MCA occlusions. The function and clinical implications of DTFV warrant further investigations.

Intracranial artery atherosclerosis and lumen dilation in cerebral small-vessel diseases: a high-resolution MRI Study.

BACKGROUND AND AIMS: Using high-resolution magnetic resonance imaging (HR-MRI), we aimed to investigate the abnormalities of intracranial artery in relation to cerebral small-vessel diseases (SVD)-related ischemic stroke and white matter lesions (WMLs). METHODS: Routine cranial MRI and HR-MRI were performed on consecutive patients with a SVD-related acute deep brain infarct (DBI) in the territory of middle cerebral artery (MCA), patients with SVD-related WMLs, and age-matched controls. The presence and distribution of MCA plaque and the area of MCA lumen and wall were comparatively analyzed among the groups. RESULTS: A total of 2340 image slices of 260 vessels in 130 subjects (57 with an acute DBI, 28 with WMLs, and 45 control subjects) were analyzed. In the patients with a DBI, eccentric plaques were identified in 26 vessels ipsilateral and 24 vessels contralateral to the ischemic lesions. Superior-wall plaques of MCA were observed more frequently ipsilateral than contralateral to the infarcts (69.2% vs. 37.5%, P = 0.025). Compared to the controls, larger outer-wall boundary area (P ≤ 0.017) and wall area (P < 0.001) were observed in the patients, while larger lumen was only observed in the WMLs group (P < 0.001). CONCLUSIONS: Middle cerebral artery superior-wall plaques are associated with acute DBIs, while MCA lumen dilation is associated with WMLs.