Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients.

Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS. Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively. Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442.

[Study of Paints and Drawing Techniques of Fine Brushwork Yunlong Ripples Painting in Qing Dynasty].

In order to study the paints and techniques of decorative patterns of dragon among clouds and water waves, the materials based on a Qing Dynasty meticulous painting were measured by three-dimensional video microscopy, Raman microscopy and energy dispersive X-ray fluorescence spectroscopy. The results showed that the green clothes was firstly colored by Paris green, the decorative patterns of dragon among clouds and water waves were then painted by hematite, the edge was delineated by brass powder at last. The dark yellow area within the decorative patterns was presented due to the interaction of green and red paints. In addition, ultramarine blue was checked in the painting. According to the first synthesized time of ultramarine blue and Paris green, we can make sure the time limit of the painting finished.

Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors.

Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by hypergastrinemia that arise from enterochromaffin-like cells of the stomach. GNETs consist of a heterogeneous group of neoplasms comprising tumor types of varying pathogenesis, histomorphologic characteristics, and biological behavior. A classification system has been proposed that distinguishes four types of GNETs; the clinicopathological features of the tumor, its prognosis, and the patient's survival strictly depend on this classification. Thus, correct management of patients with GNETs can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient. Recently developed cancer therapies such as inhibition of angiogenesis or molecular targeting of growth factor receptors have been used to treat GNETs, but the only definitive therapy is the complete resection of the tumor. Here we review the literature on GNETs, and summarize the classification, clinicopathological features (especially prognosis), clinical presentations and current practice of management of GNETs. We also present the latest findings on new gene markers for GNETs, and discuss the effective drugs developed for the diagnosis, prognosis and treatment of GNETs.

[Assessment of cognitive function, emotions and activities of daily living in patients with multiple system atrophy].

OBJECTIVE: To explore the cognitive function, emotional status and activities of daily living in patients with multiple system atrophy (MSA). METHODS: Thirty-two MSA patients and 38 healthy controls from October 2009 to November 2012 were recruited from our hospital. Their cognitive function, emotional status and activities of daily living were assessed. Cognitive function was assessed by Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE); emotional status by self-rating depression scale (SDS) and self-rating anxiety scale (SAS); daily living and activities by activities of daily living scale (ADL). Data analysis was performed with SPSS 19.0. And the results were presented as the mean ± standard deviation. Comparison of means was performed with independent sample t test. And Pearson's correlation test was used for correlation analysis. A P-value <0.05 was considered significant. RESULTS: Mild or moderate cognitive impairment was documented in 71.9% of MSA patients. The scores of MoCA and MMSE in the MSA group were significantly lower than those in the control group. And the scores of ADL, SDS and SAS in the MSA group were significantly higher than those in the control group (P < 0.05). MoCA subitems such as space/executive function, attention, abstraction, language and delayed memory of the MSA group were significantly lower than those of the control group (P < 0.05). A negative correlation existed between the scores of MoCA and MMSE with disease duration (P < 0.01). There was a positive correlation between the scores of SDS and SAS with ADL and disease duration (P < 0.05). And the relationship was significant between the scores of SDS and SAS (P < 0.01). A positive correlation existed between scores of ADL with disease duration (P < 0.05). CONCLUSION: MSA patients have certain degrees of cognitive impairment, emotion disorders and impaired ADL. Cognitive impairment in MSA patients may be more common than previously. Furthermore, the clinical features of cognitive impairment in these patients may have some clinical values for references.

[Comparative study on diagnostic significance of urethral sphincter versus external anal sphincter electromyography in patients with multiple system atrophy].

OBJECTIVE: To evaluate the diagnostic value of external anal sphincter electromyography (EAS-EMG) versus urethral sphincter electromyography (US-EMG) in patients with multiple system atrophy (MSA). METHODS: A total of 27 MSA patients were examined with EAS and US-EMG as treatment group while 28 non-MSA subjects as control group. Spontaneous activities during relaxation, mean duration & amplitude of motor unit potential (MUP), percentage of polyphasic and variations during strong contraction were recorded and analyzed statistically. RESULTS: There was significant difference in light contraction between MSA and non-MSA cases on both EAS-EMG and US-EMG (EAS-EMG, P < 0.001; US-EMG, P = 0.002) . Meanwhile, strong contraction and percentage of polyphasic showed significant differences between MSA and non-MSA cases on EAS-EMG only (strong contraction, P = 0.016; percentage of polyphasic, P = 0.004) . EAS-EMG showed more significant changes in neurogenic injury than US-EMG. CONCLUSIONS: US-EMG and EAS-EMG are valuable for the diagnosis of MSA. The differences of multiple parameters of EAS-EMG were more significant than those of US-EMG for MSA cases. US-EMG may serve as a supplement of EAS-EMG in case of restriction.

[Leukoencephalopathy with cerebral calcification and cysts: a case report and review of literature].

OBJECTIVE: To improve the diagnostic ability of leukoencephalopathy with cerebral calcifications and cysts (LCC), a rare central nervous system disease. METHODS: The clinical manifestations, neuroimages and neuropathological features of a 19-year-old male patient were analyzed. A total of 20 cases from 14 literatures were reviewed. RESULT: The patient was admitted with right limb weakness, cognitive decline, headache and blurred eyesight. Head CT scan showed multiple calcifications, cysts formation and leukoencephalopathy. Brain MRI showed several cysts in bilateral hemisphere, basal ganglia, thalamus and paraventricular areas. A mural nodule was noted inside one of the cyst, which was enhanced on the contrasted MRI. The wall of the cysts was partially enhanced, but not with the fluid inside the cysts. The corresponding CT calcifications foci showed on T1 and T2 with either both hyperintensity or both hypointensity, which was also partial enhanced. Extensive leukoencephalopathy was formed around the cysts and the ventricles. But neither Cho nor NAA changed a lot on MRS. Amplitude diagram of SWI series exhibited multiple round small dark signals all over the affected areas with mixed signals showed in the phase diagram, which indicated both calcifications and microbleeding at the lesions. Neuropathological examinations found no tumor cells in the operated cyst, and showed angiomatous small blood cells were dominant in the cyst wall. Hyaline degenerations, microcalcifications and hemosiderin deposition were observed. No obvious demyelination was discovered, while gliosis, numerous Rosenthal fibers and fibrinoid vascular necrosis were found around the lesions. The clinical, neuroimaging and pathological features of this patient were in accordance with the cases reported in the literatures. CONCLUSIONS: Neuroimaging is the most important method for the diagnosis of LCC. As small vessel lesions are probably closely related to the pathophysiology of LCC, SWI could be recommended to further reveal the etiology of LCC.

[An etiological analysis of 367 neurological outpatients with complaint of vertigo].

OBJECTIVE: To explore the etiology of patients with chief complaint of vertigo in the department of neurology in order to reduce the rate of misdiagnosis. METHODS: A total of 367 patients with chief complaint of vertigo in our department of neurology were followed up. The associated medical history, symptoms and physical examination were obtained. RESULTS: The main diagnoses for the 367 patients were benign paroxysmal positional vertigo (BPPV) (219, 59.7%), posterior circulation ischemia (PCI) (65, 17.7%), migraine (31, 8.4%), hypertension (18, 4.9%) and psychogenic vertigo (17, 4.6%). CONCLUSIONS: Presentation of vertigo can be clinically diagnosed in most diseases, with the most common cause of BPPV. Combination of the prominent clinical features, physical examinations and especially Dix-Hallpike maneuver may guide the general physicians to a most proper cause of vertigo.

[Clinical features and neuroimaging findings of 12 patients with acute disseminated encephalomyelitis involved in corpus callosum].

OBJECTIVE: To summarize the clinical features and neuroimaging findings of the patients with acute disseminated encephalomyelitis (ADEM) involved in corpus callosum (CC) so as to distinguish it from other diseases. METHODS: A total of 12 ADEM patients with the involvement of CC during the period of 2010-2012 were recruited. There were 9 males and 3 females with a mean age of 31±14 years (range: 10-54). Their clinical and neuroimaging features were retrospectively reviewed and all data analyzed by SPSS 18.0. RESULTS: (1) All of them had an acute or subacute onset. Two patients had a history of vaccination and 5 suffered upper respiratory tract infection or diarrhea. (2) The presenting symptoms included fever (n=5), headache (n=4), unsteady gait (n=2), urinary retention (n=1), indifference (n=1) and delirium (n=1). (3) The main clinical symptoms included memory loss (n=9), delirium (n=5), somnolence (n=4), urinary retention (n=9), paraplegia (n=4) and unsteady gait (n=5). (4) The examinations of cerebrospinal fluid (CSF) revealed increased intracranial pressure (n=4), leucocytosis (n=3) and increased protein (n=7) of 7 cases. All oligoclonal bands were negative. (5) The lesions were involved in bilateral CCs in 12 patients. Among them, splenium was the most commonly affected (n=9), secondly stem (n=5) and lastly genu (n=4). For 6 patients, the intracranial lesions were all in their CCs. And among them, 2 cases were involved in spinal cord. Except for CC, there were other focal lesions in brain stem and cerebellum (n=4) and spinal cord (n=6). (6) On magnetic resonance imaging (MRI), all cases showed long T2 signal intensity with blurred images. And among them, 2 cases' lesions in brain were discerned only by diffuse weighing imaging (DWI) or T2 fast fluid-attenuated inversion recovery (T2FLAIR) instead of T2-weighted. The lesions of CCs showed on gadolinium-enhanced MRI were significantly enhanced and the shapes were sheet-like (4/6). Spinal cord lesions was found in 6 cases and most spinal cord lesions were discontinuous. And the number of spinal cord segments with lesions was from 4 to 8. The shapes of lesions of spinal cord showed on enhanced MRI were like thin line. (7) Most of them were misdiagnosed as viral encephalitis (n=5), tuberculous meningoencephalitis (n=1) and brain neoplasms (n=2). And another case was admitted into urology surgery ward due to urinary retention. CONCLUSION: There are three key points about the characteristics of the ADEM patients with CC lesions: (1) They may have an adult male preponderance. The distinctive symptoms include fever, headache, delirium, somnolence, memory loss, unsteady gait and urination disorders, etc.. (2) The number of lesions on brain MRI can be multiple or single, especially the lesions of CC (mostly in splenium). On MRI, all cases showed long T2 signal intensity with blurred images so that DWI and T2 FLAIR may have a higher efficiency of detecting the lesions. In particular, multiple lesions may be all enhanced or not enhanced at equal pace on enhanced MRI. (3) In ADEM patients with CC lesions, many indices of CSF chemical examination, such as increased intracranial pressure, leucocytosis, increased protein, low sugar and low chloride, indicate the presence of intracranial infective diseases. Therefore they are most likely to be misdiagnosed as viral encephalitis or tuberculous meningoencephalitis. However, CC is not the predilection site for viral encephalitis since CC belongs to white matter but not gray matter. So ADEM should be a more appropriate diagnosis for these cases.

[The diagnostic value of urethral sphincter electromyography in patients with multiple system atrophy].

OBJECTIVE: To analyze diagnostic evaluation of urethral sphincter electromyography (US-EMGs) for patients with multiple system atrophy (MSA). METHODS: Totally 15 patients who were diagnosed as MSA were examined as treatment group while 17 non-MSA patients were examined as controls. US-EMGs were performed in the both groups. Spontaneous activities when relax, parameters of motor unit potentials (MUPs) mean duration and amplitude, percentage of polyphasic ware, satellite potential, recruitment potentials and amplitude when strong contraction were recorded and analyzed. RESULTS: US-EMGs changes of various abnormalities were found in 13 cases (86.7%) in MSA group. There were significant differences of electromyographic findings between the MSA group and control group including MUPs mean duration [(12.79 ± 3.18) ms vs (9.49 ± 1.51) ms] and amplitude [(828.53 ± 459.89) µV vs (378.76 ± 152.26) µV] as well as recruitment potentials [(11.47 ± 21.55)% vs (8.23 ± 10.74)%] and amplitude [(2.19 ± 1.24) mV vs (0.75 ± 0.42) mV] when strong contraction (all P values < 0.05). CONCLUSIONS: There is certain value of US-EMGs for the diagnosis of MSA. It could be used as a routine electrophysiological method for the patients who are suspected of MSA. It could be a supplement of external anal sphincter electromyography.

[A case report of neuromyelitis optica with 37 years' interval between optic neuropathy and spinal cord lesion and literature review].

OBJECTIVE: To improve the recolonization of long term interval between optic neuropathy and spinal cord injury of neuromyelitis optica. METHODS: One 51-year old male patient with 37 years' interval between optic neuropathy and spinal cord injury of neuromyelitis optica underwent the examination of plasma and cerebrospinal fluid and head and spinal MRI examinations, who was also followed up. His clinical data were analyzed and related literature was reviewed. RESULTS: The myelin basic protein and IgG index in his cerebrospinal fluid was high, his oligoclonal band of cerebrospinal fluid was positive, and abnormal finding in visual evoked potential. Abnormal intramedullary long T(2) signals was showed in spinal cord MRI at T(1-7) segment. When diagnosed as neuromyelitis optica, the clinical symptom and signs was improved with corticosteroid and gamma globulin therapy. The patient was in stable condition at present. CONCLUSIONS: There could be a long term interval between optic neuritis and myelitis. One should pay attention to clinical features and imaging examination of subclinical lesion in spinal cord and brain and conoid the possibility of developing neuromyelitis optica or multiple sclerosis.

[The clinical features, neuroimaging findings and pathological characteristics of 26 patients with pathologically proven tumor-like inflammatory demyelinating diseases].

OBJECTIVE: To summarize the clinical features, neuroimaging findings and pathological characteristics of 26 patients with tumor-like inflammatory demyelinating diseases (TIDD) confirmed by histopathology for better diagnosis and differential diagnosis. METHODS: The clinical features, neuroimaging findings and pathological characteristics of 26 patients (14 male, 12 female) with pathologically proven TIDD (24 brain-type and 2 spinal cord-type) were retrospectively analysed. RESULTS: The mean onset age was 6 - 69 (36.7 ± 13.8) years. Twenty-one patients had good prognosis with a median followed-up duration of 51.0 months. Two patients were died of post-operative complication and pulmonary infection respectively and the remaining 3 patients were lost to followed up. The TIDD patients almost showed monophasic clinical setting. Headache, indifference accompanied with hypothesis were the commonest initial symptoms. The positive or abnormal rates of cerebrospinal fluid oligoclonal bands (OCB) and myelin basic protein (MBP) in TIDD patients were high. The involvements of bilateral and multi-lesions were commonest in TIDD (61.5%, 65.4% respectively). Twenty-two patients with CT unenhanced scanning showed hypodense lesions. Long T(1) and long T(2) signal intensity was showed on MRI and most cases appeared round-like lesion in shape. According to the shape of enhancement of the 23 patients performed with contrast agents, 11 were shown with open-ring enhancement, 4 cases (including 2 accompanied with open-ring enhancement) with complete ring enhancement, 3 with asymmetrical dotted enhancement, 2 with diffused even enhancement, and no enhancement was seen in the other 6. Furthermore, 14 cases with DWI and 12 with FLAIR all appeared hyperdensity. The typical pathological changes were demyelinating, perivascular inflammatory cells infiltration and reactive gliosis. Occasionally, the Creutzfeldt cells were also found in brain tissue of some patients. CONCLUSIONS: TIDD is a distinct demyelinating disease entity. In spite of being apt to be confused with the neoplasm in brain and spinal cord. TIDD has its own-features, for example, OCB is frequently positive in patients with TIDD and the level of MBP may be significantly increased. Furthermore, the involvements of bilateral and multi-lesions are the common in TIDD, and most cases showed open-ring enhancement or complete rim enhancement on MRI. In addition, all cases present hypodense lesions on unenhanced CT and patients with hyperdense seemed not to be considered as TIDD.

Phenotypic patterns of MELAS/LS overlap syndrome associated with m.13513G>A mutation, and neuropathological findings in one autopsy case.

The 13513G>A mutation in the ND5 gene of mitochondrial DNA (mtDNA) is usually associated with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS), or Leigh syndrome (LS). In this study, we describe three young Chinese patients with MELAS/LS overlap syndrome who carried the m.13513G>A mutation. Clinical and MRI features were characteristic of both MELAS and LS. Interestingly, the clinical presentation of this overlap syndrome could be variable depending on the degree of relative contribution of MELAS and LS, that is, MELAS as the initial presenting syndrome, LS as the predominant syndrome, or both MELAS and LS appearing at the same time. The final brain MRI showed findings characteristic of both MELAS and LS, with asymmetrical lesions in the cortex and subcortical white matter of the occipital, temporal, and frontal lobes (MELAS), and bilateral and symmetrical lesions in the basal ganglia and brainstem (LS). Brain autopsy in one case revealed infarct-like lesions in the cerebral cortex, basal ganglia and brainstem, providing further insight into the distribution of the pathological lesions in MELAS/LS overlap syndrome. This is the first report of the brain pathological changes in a patient with m.13513G>A mutation. The spatial distribution of infarct-like lesions in the brain could explain the symptoms in MELAS/LS overlap syndrome.

[A clinical comparative study of multiple sclerosis and neuromyelitis optica.].

OBJECTIVE: To compare the clinical characteristics of multiple sclerosis (MS) and neuromyelitis optica (NMO) for better diagnosis and differential diagnosis of them. METHODS: The characteristics of 40 MS and 38 NMO cases were retrospectively studied on clinic manifestations, electroneurophysiology, some laboratory indices, imaging characteristics and so on. RESULTS: The ratios of male to female were 1:1.35 and 1:4.43 respectively in patients with MS and NMO, so patients with NMO were more likely to be female as compared with MS (P < 0.05). The mean onset age was (35.5 +/- 13.9) years in MS patients and (30.6 +/- 15.6) years in NMO patients, but no significant difference was found (P > 0.05). The cases of visual acuity

[The clinical and pathological characteristics of a patient with glycogen storage disease IV].

OBJECTIVE: To report the clinical and pathological characteristics of one patient with glycogen storage disease IV (Anderson disease). METHODS: The patient was received detailed clinical examinations, ultrasound, electromyography, head MRI and muscle biopsy. RESULTS: The onset of the 22 years old male patient was 7 yrs. The main symptoms were intolerance and fatigue in proximal limbs muscular movement, cardiopalmus by chance. Abdominal ultrasound examinations showed cirrhosis, portal hypertension, splenomegaly. Echocardiogram showed left ventricular myohypertrophia, mild mitral and tricuspid valve insufficiency. Electrophysiology study revealed widespread myogenic changes. Cranial MRI, MRA and MRS were normal. Muscle biopsy showed basophilic intracytoplasmic material in a lot of fibers deposits, which was intensively PAS-positive material and partially resistant to diastase digestion. In the electron microscope, the storage material consisted of filamentous and finely granular material. CONCLUSIONS: There was the first case of glycogen storage disease IV reported in our country, mainly involved skeletal muscle, liver, spleen and cardiac muscle.

[A study on the expression of anti-mitochondrial antibody in the brain of patients with MELAS syndrome].

OBJECTIVE: To investigate the pathological changes and pathogenesis of the MELAS syndrome (mitochondrial encephalopathy lactic acidosis stroke-like episodes) by using the method of immunohistochemical staining in the brain biopsy specimens with anti-mitochondrial antibody (AMA). METHODS: We performed immunohistochemical staining in 3 confirmed MELAS patients' paraffin-imbued brain biopsy specimens. RESULTS: Small vessel proliferation and the uneven thickness of the wall were found in the 3 MELAS patients. A lot of brown deposits was shown in the wall of small vessels and also noted in neurons. CONCLUSIONS: The main pathological change in the MELAS brain biopsy immunohistochemical staining with AMA was the small vessel proliferation, indicating that abnormal mitochondria accumulated in the vascular smooth muscle, endothelial cell and neurons of the lesion sites. This finding was consistent with the electron microscopic discovery and valuable for the diagnosis of MELAS.