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Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.
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OBJECTIVE@#To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC).@*METHODS@#Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing.@*RESULTS@#The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2).@*CONCLUSION@#The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.
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Humans , Genomics , Heterozygote , Mutation , Tuberous Sclerosis/genetics , Tuberous Sclerosis Complex 2 Protein/geneticsABSTRACT
A systematic characterization of the similarities and differences among different methods for detecting structural brain abnormalities in schizophrenia, such as voxel-based morphometry (VBM), tensor-based morphometry (TBM), and projection-based thickness (PBT), is important for understanding the brain pathology in schizophrenia and for developing effective biomarkers for a diagnosis of schizophrenia. However, such studies are still lacking. Here, we performed VBM, TBM, and PBT analyses on T1-weighted brain MR images acquired from 116 patients with schizophrenia and 116 healthy controls. We found that, although all methods detected wide-spread structural changes, different methods captured different information - only 10.35% of the grey matter changes in cortex were detected by all three methods, and VBM only detected 11.36% of the white matter changes detected by TBM. Further, pattern classification between patients and controls revealed that combining different measures improved the classification accuracy (81.9%), indicating that fusion of different structural measures serves as a better neuroimaging marker for the objective diagnosis of schizophrenia.
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A systematic characterization of the similarities and differences among different methods for detecting structural brain abnormalities in schizophrenia, such as voxel-based morphometry (VBM), tensor-based morphometry (TBM), and projection-based thickness (PBT), is important for understanding the brain pathology in schizophrenia and for developing effective biomarkers for a diagnosis of schizophrenia. However, such studies are still lacking. Here, we performed VBM, TBM, and PBT analyses on T1-weighted brain MR images acquired from 116 patients with schizophrenia and 116 healthy controls. We found that, although all methods detected wide-spread structural changes, different methods captured different information - only 10.35% of the grey matter changes in cortex were detected by all three methods, and VBM only detected 11.36% of the white matter changes detected by TBM. Further, pattern classification between patients and controls revealed that combining different measures improved the classification accuracy (81.9%), indicating that fusion of different structural measures serves as a better neuroimaging marker for the objective diagnosis of schizophrenia.
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Objective@#To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy.@*Methods@#Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing.@*Results@#The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c. 2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents.@*Conclusion@#The recurrent frame-shifting mutation c. 2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.
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OBJECTIVE@#To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy.@*METHODS@#Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing.@*RESULTS@#The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c.2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents.@*CONCLUSION@#The recurrent frame-shifting mutation c.2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.
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Female , Humans , Diagnostic Errors , Epilepsy , Diagnosis , Genetics , Frameshift Mutation , Tuberous Sclerosis , Diagnosis , Genetics , Tuberous Sclerosis Complex 1 Protein , Genetics , Tuberous Sclerosis Complex 2 Protein , GeneticsABSTRACT
Objective To identify Chinese character writing related cortex (WRC) and its relationship with hand motor cortical areas. Methods Ten native Chinese-speaking, right-hand volunteers were recruited in the study. NTMS mapping was conducted during picture naming task. The WRC were mapped based on nTMS-induced impairment of Chinese character writing. The extent and area of WRC was calculated. The right-hand motor representations were mapped while motor-evoked potentials were produced under nTMS stimulation. EMG data and coordinates of positive stimulus were recorded. The relationship between WRC and hand motor cortex (HMC) was analyzed on the basis of area comparison and distance calculation. Results The cortical areas related to Chinese character writing were mapped successfully in all subjects by nTMS. WRC was primarily centered in left posterior middle frontal gyrus (pMFG) (86%,55/64). The mean WRC area (161.03 mm2 ±62.58mm2) was significantly smaller than the mean HMC area (589.50 mm2±227.34mm2) (P<0.001). The WRC and HMC were not conjoined or overlapped in the dominant hemisphere. The distance between those two was 12.58mm±2.71mm. Conclusions NTMS can provide reliable assistance in mapping WRC areas. The WRC is relatively fixed and centralized in pMFG but is not overlapped with the HMC.
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OBJECTIVE: This experiment aims to determine the diagnostic value of diffusion-weighted imaging (DWI) in the differentiation of axillary inflammatory lymph nodes from metastatic lymph nodes in rabbit models in comparison with conventional magnetic resonance imaging (MRI). MATERIALS AND METHODS: Conventional MRI and DWI were performed at 4 weeks after successful inoculation into the forty female New Zealand white rabbits' mammary glands. The size-based and signal-intensity-based criteria and the relative apparent diffusion coefficient (rADC) value were compared between the axillary inflammatory lymph nodes and metastatic lymph nodes, with histopathological findings as the reference standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the aforementioned criteria and rADC value in differentiating the axillary inflammatory lymph nodes from metastatic lymph nodes. RESULTS: Thirty-two axillary inflammatory lymph nodes and 46 metastatic ones were successfully isolated and taken into pathological analysis. The differences of the aforementioned criteria between the two groups were not statistically significant (p > 0.05). However, the rADC value of the inflammatory lymph nodes (0.9 +/- 0.14) was higher than that of metastatic ones (0.7 +/- 0.18), with significant difference (p = 0.016). When the rADC value was chosen as 0.80, the area under the ROC curve is greater than all other criteria, and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for differentiating two groups were 86.2%, 79.3%, 81.2%, 84.2%, and 85.6%, respectively. CONCLUSION: Diffusion-weighted imaging is a promising new technique for differentiating axillary inflammatory lymph nodes from metastatic lymph nodes. Compared with routine magnetic resonance sequences, DWI could provide more useful physiological and functional information for diagnosis.
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Animals , Female , Rabbits , Axilla , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging , Inflammation/pathology , Lymphatic Metastasis/pathology , Magnetic Resonance Imaging/methods , Mammary Neoplasms, Experimental/pathology , ROC Curve , Sensitivity and SpecificityABSTRACT
Objective To study the correlation between novelty seeking(NS) personality of healthy young individuals and fractional anisotropy (FA) with voxel-based analysis (VBA) of diffusion tensor imaging(DTI),and explore the microstructure of white matter of personality.Methods Total 333 healthy right handed volunteers completed the Chinese version of the TPQ and the Beck Depression Inventory(BDI),and then finished 3D T1 structure scan,DTI scan.All preprocessed DTI datum was analyzed with SPM8 soft ware in partial correlation analysis,using age and depression scores as controlled variable.The correlation studied between NS and FA (a voxel significance threshold P ＜ 0.001 and a cluster extent threshold of 30 voxels).Results NS score of men and women were 14.55 ± 4.66 and 14.08 ± 5.42 points,and the difference between the two groups was not statistically significant (t =0.81,P=0.46).BDI score of men were higher than that of women (t =3.10,P=0.002),which were 9.23 ± 7.90 and 6.76 ± 5.79 points respectively.NS correlated negatively with FA of the right inferior frontal gyrus,and the right supramarg(i)nal gyrus(P ＜ 0.001).Conclusion NS personality has specific microstructure background of white matter.
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Objective To investigate the feature of regional grey matter volume changes in relapsing-remitting multiple sclerosis (RRMS) patients by voxel-based morphometry ( VBM) and presume the possible pathophysiological basis.Methods Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 32 RRMS and 32 sex- and age-matched normal controls.The comparison of grey matter volume between the two groups was analyzed by statistical analysis software SPM5 and VBM.A Pearson correlational analysis was used to assess correlation between gre matter loss and disease duration,expanded disability status scale (EDSS) and visible brain lesion volume.Results Compared with normal controls,RRMS patients had extensive bilateral grey matter atrophy in thalami (left 2031 and right 1711),caudate (left 815 and right 1031) and parahippocampal gyrus (left 313 and right 467),as well as several cortical regions in frontal,temporal,parietal,and occipital lobes (t value were between 8.853 and 11.163,all P ＜ 0.01).Regional grey matter loss in bilateral thalami ( r value were - 0.596 on left and were - 0.694 on right) and right caudate ( r = - 0.409 ) were strongly negatively correlated with visible brain lesion volume in RRMS (all P ＜ 0.05 ).Conclusions By means of VBM,extensive grey matter atrophy are found in RRMS patients,especially in deep grey matter.Axonal degeneration secondary to visible brain lesions may be a key pathogenesis of grey matter atrophy in RRMS.
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Objective To investigate the value of macrophage activity imaging (MAI) in the diagnosis of brain and spinal cord lesions in rat model of multiple sclerosis(MS). Methods Twenty LEW rats were divided into 15 model rats and 5 control rats. MS animal model, experimental autoimmune encephalomyelitis (EAE) was induced by the injection of peptide 35-55 of myelin oligodendrocyte glycoprotein ( MOG35-55 ). MRI was performed on the third day of the acute stage of disease. The brain and spinal cord of rats were scanned by 3.0 T MR scanner( Siemens Trio Tim) with quadrature wrist joint coil.The T2W and T1 W images, Gadolinium enhanced T1 W images in 3D volume were obtained respectively. The MAI were obtained at 24 hours after intravenous injection of ultra small superparamagnetic iron oxide (USPIO) as contrast medium on T2WI. The workstation with special software was used for the reconstruction images of brain and spinal cord of rat in multiple orientations. Results Fifteen MOG35-55-EAE rats model of MS were successfully induced. The great majority lesions of central nervous system in acute stage were located in the brain( 58/63 ) and less in the spinal cord (5/63). The main manifestation of EAE lesions presented was hyperintensity on T2 WI and hypointensity on T1 WI, and some lesions had enhancement after Gd-DTPA injection. The EAE lesions presented as hypointensity on MAI images, but some of them were found to be isointensity on T2 WI. The enhancement pattern was discrepant between USPIO and Gd-DTPA.The sensitivity of depicting lesions of MOG35-55-EAE rat at acute stage were higher on T2WI ( 14/15 ) and MAI ( 13/15 ), and the detection rate was 100% ( 15/15 ) if they were combined. Gd-DTPA enhanced T1 WI had a lower sensitivity (7/15). All the MAI findings were negative in the control rats. Conclusions MAI can complement the drawback of conventional MRI techniques by continuously monitoring the inflammatory activity of EAE lesions, and it could raise the detection rate of EAE lesions by combining with T2WI. Gd-DTPA enhanced T1 WI monitors the breakdown of the blood brain barrier. MAI and Gd-DTPA enhanced MR imaging are complementary in the diagnosis and monitoring of EAE lesions.
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Objective To investigate the mechanism of capsaicin in treating active psoriasis vulgaris. Methods A total of 42 patients with active psoriasis vulgaris diagnosed by histology and clinical features were given either placebo or 0.025% capsaicin ointment four times daily for 30 days randomly by double-blind method. Vasoactive intestinal polypeptide receptor 1(VIPR1) gene translation in active psoriatic lesions before and after treatment with capsaicin ointment was detected by in situ hybridization. Results There was positive staining of VIPR1 gene in all the layers of psoriatic epidermis (95.5%) before the treatment with capsaicin ointment, but nearly no dyeing in epidermis (18.2%) after the treatment for 30 days. There was nearly no brown staining before and after treatment in control group. Conclusion VIPR1 gene translation in psoriatic epidermis is down-regulated after capsaicin treatment for 30 days.
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at model is an ideal MS model for clinical MRI study.
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Objective To observe whether repetition time (TR) and field strengths have effects on diffusion indices of brain white matter. Methods Seven rhesuses underwent diffusion tensor MR imaging (DT-MRI) with a series of TRs (from 500 to 6000 ms) at 1.5T and 3.0T MR scanners, respectively. The mean diffusivity (MD), fractional anisotropy (FA), primary (λ1) and transverse eigenvalues (λ2, 3) were measured in region of interest (ROI) at the posterior limb of internal capsule. Pearson correlation analysis and two-way ANOVA were performed. Results None of the diffusion indices was correlated with TR (P＞0.05) when SNR was high enough (SNR>35). FA was significantly higher and the MD and λ2, 3 were significantly lower at 3.0T than those at 1.5T (P＜0.001). No significant difference of λ1 was found between the two field strengths (P＞0.05). Conclusion Field strength may influence diffusion quantification, but not for TR, which should be considered in multi-center studies.
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Objective To explore the feasibility of using clinical whole body MR scanners to investigate the intravital visibility of central nervous system (CNS) lesions in rats of multiple sclerosis (MS). Methods Ten Lewis rats were injected with the peptide 35-55 of myelin oligodendrocyte glycoprotein to make the model of MS. On a Siemens Sonata 1.5T MR scanner equipped with a flexible surface coil, rats brain and spinal cord were examined using T2-weighted and T1-weighted imaging with slice thickness of 1-2 mm. On a Siemens Trio Tim 3.0T MR-scanner equipped with a quadrature wrist coil, rats were examined using T2WI, T1WI and Gd-DTPA enhanced T1WI 3-dimensional imaging with voxel size up to 0.06-0.08 mm~3. Rat brain and spinal cord images in multiple orientations were reconstituted with special software in workstation. Results T2WI and T1WI of the lesions in MS rat brain with high spatial and contrast resolution could be obtained with clinical 3.0T MR scanner, though the image resolution of spinal cord was relatively low. The resolution of 1.5T MR was lower than that of 3.0T. Plaques in CNS of MS rats presented as hyperintense areas on T2WI and hypointense areas on T1WI. Contrast enhancement was observed as hyperintense on T1WI. Conclusion High quality images of CNS lesions canbe obtained with clinical 3.0T MR-scanner in MS rat, which offers a noninvasive access for studying CNS diseases in the rats.
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Objective Using manganese enhanced MR imaging(ME-MRI)as a standard to validate the accuracy of white matter diffusion tenor tractography(DTT)with different gradients orientations in macaque monkeys.Methods Seven adult male macaque monkeys were scanned for DTY images with different number of gradients orientations.When all data were acquired.3 μl of 0.8 mol aqueous solution of MnCl2 was injected into the primary motor cortex representing forelimb for ME-MRI scanning 48 hours later.On the images of fractional anisotropy(FA),seed region for fiber tracking was chosen according to the subcortical enhanced range on ME-MRI,then the DTT fiber tracts proiecting on axial images of FA were compared with enhancement region on T1WI of ME-MRI.Results Under the calculation method for fiber tracking in the study,different motion-probing gradients orientations led to results consistent with ME-MRI for the brain above the midbrain level.All group's concordance score of fibertracking results were good.Among them,30 and 64 orientation fiber tracking results were optimal.Below the midbrain level,there was significant difference between DTT fiber tracking and ME-MRI fiber tracking. Conclusion Different motion-probing gradients orientations do not influence DTT fiber tracking.But below the midbrain level.the results of DTT fiber tracking were not reliable according to the standard results of ME-MRI fibe tracking.
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Objective To investigate the evolution of diffusion indices in the pyramidal tract with Wallerian degeneration(WD)due to cerebral infarction using diffusion tensor imaging(DTI),and to study the relationship between early changes of diffusion indices and motor deficit.Methods Fifteen patients (13 males and 2 females)with acute cerebral infarction(within 7 days)were recruited from the Neurology Department from Mar 2006 to Jan 2007.A11 patients were assessed with DTI.National Institutes of Health Stroke Scale(NIHSS),Bathel Index(BI),modified Rankin Scale(mRS)and Motricity Index(MI)within 7 days from onset,and at the second week.DTI was performed with SIEMENS Trio 3.0 T MR scanner.The placement of region of interest(ROI),measurement of diffusion indices were performed by DTI Studio software.The mean diffusivity(MD),the fractional anisotropy(FA),the first eigenvalue (λ1),the second eigenvalue(λ2),and the third eigenvalue(λ3)were computed.Results At the second week.NIHSS was 6.93±3.39.BI 45.33±26.01,mRS 4.33±0.90.and MI 69.47± 60.71.At the second week from onset.MD of the pyramidal tract at the levels of the middle slice of pons and the superior slice of medulla oblongata showed no significant differences between both the two sides at second week from onset. Other ROI showed significant differences between both sides.MD.FA and λ1 of affected side were lower than the unaffected side.λ2 and λ3 of the affected side were higher than the unaffected side.Positive correlations were found between FA and BI(r=0.530,P=0.042),FA and MI(r=0.543,P=0.036)at the second week.Negative correlations were found between FA and NIHSS(r=-0.613,P=0.015)at the second week.Conclusions DTI can detect the changes in the pyramidal tract due to WD within 7-14 days after ischemic stroke.including a decrease of the fractional anisotropy.the first eigenvalue and increased the second and the third eigenvalues.The fractional anisotropy of the second week from onset is related to the outcome of the motor function.
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Objective To investigate whether abnormalities can be detected in normal-appearing white matter(NAWM)and normal-appearing white matter(NAGM)in patients with clinically isolated syndrome(CIS)and comparing them to the abnormalities in relapsing-remitting multiple sclerosis(RRMS)by using diffusion tensor imaging(DTI)histogram.To detect the potential relationship between DTI indices of NAWM,NAGM and patient's clinical condition.Methods Nineteen patients with CIS,19 clinically diagnosed RRMS patients and 19 sex-and age-matched healthy volunteers were included in this study.Conventional MRI and DTI images were obtained using Siemens 1.5 T Magnetom sonata scanner.DTI histograms of NAWM and NAGM were obtained after post-processing.The mean value,peak height,peak location of the histogram were used for analysis.All data was statistically processed with SPSS for Windows.Results NAWM average MD was higher and FA was lower in RRMS[MD(0.83±0.04)×10-3mm2/s,FA 0.36±0.03]when compared to CIS[MD(0.79±0.02)×10-3mm2/s,FA 0.40±0.02]and control[MD(0.78±0.02)×10-3mm2/s,FA 0.41±0.01](P＜0.01).But no statistically significant difference was found between CIS and control.The peak height of NAWM average MD histogram was significantly lower in CIS than control(P＜0.05),while the peak location of average FA histogram shifted to the left(P＜0.01).Patients with CIS[(1.08±0.06)×10-3mm2/s]showed significantly higher NAGM average MD than control[(1.03±0.05)×10-3mm2/s](P＜0.05),but,lower than RRMS[(1.18±0.12)×10-3mm2/s](P＞0.01).There were no correlation between DTI indices and EDSS scores in patients with CIS.Moderate correlation between NAGM average MD(r=0.568,P＜0.05)and EDSS scores were found in patient with RRMS.Conclusion NAWM and NAGM abnormalities do occur in CIS which can be detected by DTI.The underlying pathological changes in NAWM and NAGM in CIS may be milder than RRMS as demonstrated by DTI histogram.
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Objective To compare magnetization transfer and diffusion characteristics of multiple sclerosis(MS)lesions,normal-appearing white matter(NAWM)from patients,and normal white matter from control subjects,and to investigate the correlation between the magnetization transfer ratio(MTR)and mean diffusivity(MD)in MS patients.Methods Conventional MRI,magnetization transfer imaging(MTI)and diffusion tensor imaging(DTI)were performed in 24 relapsing remitting MS patients and 24 healthy volunteers.Based on these images,the MTR,MD and fractional anisotropy(FA)maps were obtained.Then the MTR,MD and FA values were measured in lesions and NAWM from patients,and in the relevant white matter regions from volunteers.Results Average MTR in lesions(23.49%?5.16%)from MS patients was lower than those both in NAWM(29.49%?3.38%)and in the counterparts of the controls(32.78%?3.42%,F=101.44,P
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<p><b>OBJECTIVES</b>To explore shape and position relationship of the structures with in sinus triangle region, and provide the anatomic foundation for extended presigmoid operative approach.</p><p><b>METHODS</b>Ten cadaveric heads and 15 skull-base specimens fixed with 10% formalin, with aid of operative microscope, the shape and relations of structures with in the sinus triangle region were observed and microphotographed. Four cadaveric heads were sectioned in different plane using collodion embedding process.</p><p><b>RESULTS</b>Jugular blub (JB) had high -placed jugular blub (HJB), normal jugular blub (NJB) and low-placed jugular blub (LJB). The incidence of HJB was 8% and 18% for the left and right sides (P < 0.01). The JB dome can extend upward the hypotympanic cavity and the posterior wall of the internal acoustic meatus. The incidence of NJB and LJB was 36% and 30%, and 6% and 2% respectively. The level distance between the posterior semicircular canal and petrosal posterior surface was (4.1 +/- 1.1) mm. The distance between the JB and vertical part of the facial nerve was (3.2 +/- 0.5) mm and (2.0 +/- 0.4) mm. The distance between the JB and posterior margin of the internal acoustic port was (7.5 +/- 1.7) mm and (4.0 +/- 1.0) mm.</p><p><b>CONCLUSIONS</b>Knowing the shape and position relationship of structures in the sinus triangle region is favorable for preserving the important structures in extended presigmoid operative approach.</p>