[Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5].

OBJECTIVE: To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme. METHODS: The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests. RESULTS: Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001). CONCLUSION: For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.

[Mitochondrial respiratory chain complex I deficiency due to 10191T>C mutation in ND3 gene].

This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191T>C mutation in mitochondrial ND3 gene. The previously healthy boy progressively presented with blepharoptosis, weakness, epilepsy and motor regression at age 6 years. Elevated blood lactate and pyruvate were observed. Brain magnetic resonance imaging showed symmetrical lesions in the basal ganglia. Leigh syndrome was thus confirmed. The protein from the mitochondria and genomic DNA of the boy and his parents was collected from peripheral blood leucocytes for the activity test for mitochondrial complex I to V and genetic analysis. The results showed the activity of complex I (33.1 nmol /min in 1 milligram mitochondrial protein) was lower than normal reference value (44.0±5.4 nmol /min in 1 milligram mitochondrial protein). The ratio of complex I to citrate synthase (19.8%) was also lower than normal reference value (48%±11%). The activities of complexes II to V were normal. 10191T>C mutation in ND3 gene of mitochondria was identified in the boy. 10191T>C mutation and complex I deficiency were not detected in his parents. At present, he is 16 years old, and of normal intelligence with spastic paralysis in both lower extremities after treatment. It is concluded that a Chinese boy with isolated complex I deficiency due to 10191T>C mutation in ND3 gene was firstly diagnosed by peripheral leukocytes mitochondrial respiratory chain enzyme assay and gene analysis. This study can provide clinical data for the nosogenesis of Leigh syndrome.

[Leucodystrophy induced by late onset 3-hydroxy-3-methylglutaric aciduria].

3-Hydroxy-3-methylglutaric aciduria is a rare disorder of organic acid metabolism caused by 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. The disorder was common in neonatal or infant period. Here a case of late onset 3-hydroxy-3-methylglutaric aciduria complicated by leucodystrophy was reported. The patient was a 7-year-old boy. He presented with progressive headache, drowsiness and vomiting. Hepatic lesions, ketosis and leucopenia were found. Symmetrical diffused leucodystrophy was shown by MRI. Blood levels of isovalerylcarnitine and acetylcarnitine increased significantly. Urinary levels of 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-hydroxyglutaric acids and 3-methyl-crotonylglycine increased significantly. Symptoms were released by intravenous infusion of L-carnitine and glucose. After treatment for 6 months, urinary levels of 3-hydroxy-3-methylglutaric aciduria decreased in the boy and his health improved.

[Leigh syndrome due to mitochondrial respiratory chain complex II deficiency].

Mitochondrial respiratory chain complex II deficiency is a rare documented cause of mitochondrial diseases. This study reported a case of Leigh syndrome due to isolated complex II deficiency. A boy presented with progressive weakness, motor regression and dysphagia after fever from the age of 8 months and hospitalized at the age of 10 months. Elevated blood levels of lactate and pyruvate were observed. Brain magnetic resonance image showed symmetrical lesions in the basal ganglia. Mitochondrial respiratory chain complex I-V activities in peripheral leukocytes were measured using spectrophotometric assay. Mitochondrial gene screening of common point mutations was performed. The complex II activity in the peripheral leukocytes decreased to 21.9 nmol/min per mg mitochondrial protein (control: 47.3±5.3 nmol/min per mg mitochondrial protein). The ratio of complex II activity to citrate synthase activity (22.1%) also decreased (control: 50.9%±10.7 %). No point mutation was found in mitochondrial DNA. The boy was diagnosed as Leigh syndrome due to isolated complex II deficiency. Psychomotor improvements were observed after the treatment. The patient is 22 months old and in a stable condition.

[A case of Leigh syndrome associated with respiratory chain complex I deficiency due to mitochondrial gene 13513G>A mutation].

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.

T2 Mapping and Fat Quantification of Thigh Muscles in Children with Duchenne Muscular Dystrophy.

Quantitative magnetic resonance image (MRI) in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy (DMD). The purpose of this study was to measure T2 relaxation time of thigh muscles in children with DMD and healthy boys, and to correlate the T2 relaxation time of muscles with the fat fraction (FF) at quantitative magnetic resonance and results of clinical assessment. Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI. Age, body mass index (BMI), muscle strength assessment, timed functional tests (time to walk or run 10 metres, rise from the floor and ascend four stairs), and the North Star Ambulatory Assessment (NSAA) were evaluated. Spearman's correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time. The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group (P<0.05), except for the gracilis (P=0.952). The gracilis, sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients. The T2 relaxation time was correlated significantly with the mean FF in all muscles. Age, BMI, total muscle strength score, timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time. T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.

Identification in Chinese patients with GLIALCAM mutations of megalencephalic leukoencephalopathy with subcortical cysts and brain pathological study on Glialcam knock-in mouse models.

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare neurological degenerative disorder caused by the mutations of MLC1 or GLIALCAM with autosomal recessive or autosomal dominant inheritance and a different prognosis, characterized by macrocephaly, delayed motor and cognitive development, and bilateral abnormal signals in cerebral white matter (WM) with or without cysts on magnetic resonance imaging (MRI). This study aimed to reveal the clinical and genetic features of MLC patients with GLIALCAM mutations and to explore the brain pathological characteristics and prognosis of mouse models with different modes of inheritance. METHODS: Clinical information and peripheral venous blood were collected from six families. Genetic analysis was performed by Sanger sequencing of GLIALCAM. GlialcamArg92Trp/+ and GlialcamLys68Met/Thr132Asn mouse models were generated based on mutations from patients (c.274C>T(p.Arg92Trp) (c.203A>T(p.Lys68Met), and c.395C>A (p.Thr132Asn))). Brain pathologies of the mouse models at different time points were analyzed. RESULTS: Six patients were clinically diagnosed with MLC. Of the six patients, five (Pt1-Pt5) presented with a heterozygous mutation in GLIALCAM (c.274C>T(p.Arg92Trp) or c.275G>C(p.Arg92Pro)) and were diagnosed with MLC2B; the remaining patient (Pt6) with two compound heterozygous mutations in GLIALCAM (c.203A>T (p.Lys68Met) and c.395C>A (p.Thr132Asn)) was diagnosed with MLC2A. The mutation c.275C>G (p.Arg92Pro) has not been reported before. Clinical manifestations of the patient with MLC2A (Pt6) progressed with regression, whereas the course of the five MLC2B patients remained stable or improved. The GlialcamArg92Trp/+ and GlialcamLys68Met/ Thr132Asn mouse models showed vacuolization in the anterior commissural WM at 1 month of age and vacuolization in the cerebellar WM at 3 and 6 months, respectively. At 9 months, the vacuolization of the GlialcamLys68Met/ Thr132Asn mouse model was heavier than that of the GlialcamArg92Trp/+ mouse model. Decreased expression of Glialcam in GlialcamArg92Trp/+ and GlialcamLys68Met/ Thr132Asn mice may contribute to the vacuolization. CONCLUSIONS: Clinical and genetic characterization of patients with MLC and GLIALCAM mutations revealed a novel mutation, expanding the spectrum of GLIALCAM mutations. The first Glialcam mouse model with autosomal recessive inheritance and a new Glialcam mouse model with autosomal dominant inheritance were generated. The two mouse models with different modes of inheritance showed different degrees of brain pathological features, which were consistent with the patients' phenotype and further confirmed the pathogenicity of the corresponding mutations.

Muscle Magnetic Resonance Imaging in Patients with Various Clinical Subtypes of LMNA-Related Muscular Dystrophy.

BACKGROUND: LMNA-related muscular dystrophy can manifest in a wide variety of disorders, including Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), and LMNA-associated congenital muscular dystrophy (L-CMD). Muscle magnetic resonance imaging (MRI) has become a useful tool in the diagnostic workup of patients with muscle dystrophies. This study aimed to investigate whether there is a consistent pattern of MRI changes in patients with LMNA mutations in various muscle subtypes. METHODS: Twenty-two patients with LMNA-related muscular dystrophies were enrolled in this study. MRI of the thigh and/or calf muscles was performed in them. The muscle MRI features of the three subtypes were compared by the Mann-Whitney U-test. The relationship between the clinical and MRI findings was also investigated by Spearman's rank analyses. RESULTS: The present study included five EDMD, nine LGMD, and eight L-CMD patients. The thigh muscle MRI revealed that the fatty infiltration of the adductor magnus, semimembranosus, long and short heads of the biceps femoris, and vasti muscles, with relative sparing of the rectus femoris, was the predominant change observed in the EDMD, LGMD, and advanced-stage L-CMD phenotypes, although the involvement of the vasti muscles was not prominent in the early stage of L-CMD. At the level of the calf, six patients (one EDMD, four LGMD, and one L-CMD) also showed a similar pattern, in which the soleus and the medial and lateral gastrocnemius muscles were most frequently observed to have fatty infiltration. The fatty infiltration severity demonstrated higher scores associated with disease progression, with a corresponding rate of 1.483 + 0.075 × disease duration (X) (r = 0.444, P = 0.026). It was noteworthy that in six L-CMD patients with massive inflammatory cell infiltration in muscle pathology, no remarkable edema-like signals were observed in muscle MRI. CONCLUSIONS: EDMD, LGMD and advanced-staged L-CMD subtypes showed similar pattern of muscle MRI changes, while early-staged L-CMD showed somewhat different changes. Muscle MRI of L-CMD with a muscular dystrophy pattern in MRI provided important clues for differentiating it from childhood inflammatory myopathy. The fatty infiltration score could be used as a reliable biomarker for outcome measure of disease progression.

Detection of abnormal visual cortex in children with amblyopia by voxel-based morphometry.

PURPOSE: To detect the abnormalities of gray matter in children with amblyopia by voxel-based morphometry (VBM). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Thirteen children with amblyopia and 14 normally sighted children underwent magnetic resonance (MR) examination. The two groups were age-matched with a mean age of 5.8 years. In the amblyopia group, five children had strabismus amblyopia, and eight had anisometropic amblyopia. We analyzed the original 3-dimensional T1 brain images using the VBM module within the widely used analysis software package SPM2 (Welcome Department of Cognitive Neurology, London, United Kingdom). After normalization, segmentation, and smoothing of the images, comparison between amblyopic and control groups was derived for the gray matter of the entire brain using parametric statistics. RESULTS: The results of VBM analysis indicated that the amblyopic group had decreased gray matter density in the middle frontal gyrus, parahippocampal gyrus, fusiform gyrus, inferior temporal gyrus of the left hemisphere, and the bilateral calcarine cortices. The radii of these regions ranged from 12 to 36 voxels. These abnormalities were consistent with morphologic changes in brain regions related to visual function. CONCLUSIONS: Using MR and VBM analysis, we detected morphologic changes in the visual cortex of children with amblyopia, which may indicate developmental abnormalities of visual cortex during the critical growth period.

[Leigh syndrome due to pyruvate dehydrogenase E1 alpha subunit gene mutation: a complicated and difficult case study].

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs' cycle. Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome. In this study, one Chinese case of PDHA1 deficiency was reported. The patient was a boy with normal mental development, retarded motor development, general weakness, hypotonia and areflexia. Muscle histopathological findings suggested axonal peripheral neuropathy. Brain magnetic resonance imaging at 5 years of age revealed bilateral putamina lesions and periventricular white matter demyelination, supporting the diagnosis of Leigh syndrome. A C214T mutation in exon 3 of the PDHA1 gene was detected. After the treatment of thiamin, coenzyme Q10, Lcarnitine and carbohydrates-restricted diet, his movement ability improved significantly. At present, the patient is 8 years old and has normal school life. PDHA1 deficiency is an X-linked inherited metabolic disease, which shares various clinical manifestations and leads to difficult diagnosis. This patient predominately presented with progressive weakness and was diagnosed by gene analysis.

3.0 T magnetic resonance myocardial perfusion imaging for semi-quantitative evaluation of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

This study aimed to assess coronary microvascular dysfunction (CMD) differences in hypertrophic cardiomyopathy (HCM) patients using cardiac magnetic resonance (CMR) first-pass perfusion and late gadolinium enhancement imaging. Forty-seven patients with HCM and twenty-one healthy volunteers underwent CMR at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late gadolinium enhancement (LGE). Left ventricular end-diastolic wall thickness (EDTH), LGE, time to peak (Tpeak), maximal up-slope (Slopemax), and peak signal intensity (SIpeak) were assessed for each myocardial segment. The HCM myocardial segments were grouped by the degree of LGE and hypertrophy. Tpeak, SIpeak, Slopemax and EDTH in multiple groups were assessed and compared by ANOVA test/Kruskal-Wallis test. The Spearman correlation test was used to determine the relationships between EDTH, LGE and perfusion parameters (Tpeak, Slopemax and SIpeak). Compared to control group segments, Tpeak increased while Slopemax and SIpeak decreased in non-LGE/non-hypertrophic segments and LGE/hypertrophic segments in the HCM group, while Tpeak increased more significantly in LGE/hypertrophic segments (all p < 0.05). Tpeak statistically increased with increasing degrees of myocardial LGE (p < 0.01). Differences in Tpeak, SIpeak and EDTH were observed between segments with and without hypertrophy (p < 0.05). EDTH and LGE were positively correlated with Tpeak (r = 0.279, p = 0.031 and r = 0.237, p < 0.001). 3.0 T magnetic resonance myocardial perfusion imaging identifies abnormal perfusion in non-LGE and non-hypertrophic segments of HCM patients, and it may be helpful in the early diagnosis of coronary microvascular dysfunction in HCM. This abnormal perfusion is associated with the severity of myocardial fibrosis and the degree of hypertrophy.

Quantification of cerebral blood flow by flow-sensitive alternating inversion recovery exempting separate T1 measurement in healthy volunteers.

BACKGROUND: The feasibility of the mapping of quantitative cerebral blood flow (CBF) named flow-sensitive alternating inversion recovery exempting separate T1 measurement (FAIREST) is still controversial. This study aimed to evaluate the reliability of FAIREST in the measurement of regional CBF (rCBF) in healthy volunteers. METHODS: Eighteen healthy volunteers underwent magnetic resonance (MR) scanning with the sequence of FAIREST. While they were at rest, rCBF values were obtained in various brain regions of interest (ROIs). The same scheme was repeated on every subject after two weeks. Statistical analysis was made to determine the effect of location, scan and side on the measurement of rCBF. RESULTS: The mean CBF values were (122+/-28) ml x (100 g)(-1) x min(-1) and (43+/-10) ml x (100 g)(-1) x min(-1) in the gray and white matter respectively. There was significant main effect of location (t=-12.5, P<0.01), but no significant effect of side. Paired t-test of ROIs in the same slice showed no significant difference in most sites between two scans, except in the gray matter of the bilateral frontal lobes (t=2.18-2.34, P <0.05). However, the rCBF values of the same structure obtained from different slices showed a significant difference (t=-3.49, P<0.01). CONCLUSION: FAIREST is a reliable technique in the measurement of rCBF, but different imaging slice may affect the agreement of rCBF across the scans.

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome.

BACKGROUND: Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. METHODS: Sixty-five unrelated cases (35 men and 30 women) who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography (CT) scan or magnetic resonance imaging (MRI). The differential diagnosis of organic acidurias and fatty acid beta-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA (T8993G, T8993C, T9176C, A8344G, A3243G) were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 (26.2%) of the patients. The diagnosis was confirmed by autopsy in 6 (9.2%) patients. RESULTS: The patients had various forms of metabolic encephalomyopathy. Fifty-nine (90.8%) of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty (30.8%) patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases (7.7%). Of these, the A8344G mutation was detected in 2 patients. The T8993G, T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. A G604C mutation was identified in 6 (9.2%) patients. The genotypes of 52 patients remained unknown. CONCLUSIONS: Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.

"Target" and "Sandwich" Signs in Thigh Muscles have High Diagnostic Values for Collagen VI-related Myopathies.

BACKGROUND: Collagen VI-related myopathies are autosomal dominant and recessive hereditary myopathies, mainly including Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM). Muscle magnetic resonance imaging (MRI) has been widely used to diagnosis muscular disorders. The purpose of this study was to evaluate the diagnostic value of thigh muscles MRI for collagen VI-related myopathies. METHODS: Eleven patients with collagen VI gene mutation-related myopathies were enrolled in this study. MRI of the thigh muscles was performed in all patients with collagen VI gene mutation-related myopathies and in 361 patients with other neuromuscular disorders (disease controls). T1-weighted images were used to assess fatty infiltration of the muscles using a modified Mercuri's scale. We assessed the sensitivity and specificity of the MRI features of collagen VI-related myopathies. The relationship between fatty infiltration of muscles and specific collagen VI gene mutations was also investigated. RESULTS: Eleven patients with collagen VI gene mutation-related myopathies included six UCMD patients and five BM patients. There was no significant difference between UCMD and BM patients in the fatty infiltration of each thigh muscle except sartorius (P = 0.033); therefore, we combined the UCMD and BM data. Mean fatty infiltration scores were 3.1 and 3.0 in adductor magnus and gluteus maximus, while the scores were 1.3, 1.3, and 1.5 in gracilis, adductor longus, and sartorius, respectively. A "target" sign in rectus femoris (RF) was present in seven cases, and a "sandwich" sign in vastus lateralis (VL) was present in ten cases. The "target" and "sandwich" signs had sensitivities of 63.6% and 90.9% and specificities of 97.3% and 96.9% for the diagnosis of collagen VI-related myopathies, respectively. Fatty infiltration scores were 2.0-3.0 in seven patients with mutations in the triple-helical domain, and 1.0-1.5 in three of four patients with mutations in the N- or C-domain of the collagen VI genes. CONCLUSIONS: The "target" sign in RF and "sandwich" sign in VL are common MRI features and are useful for the diagnosis of collagen VI-related myopathies. The severity of fatty infiltration of muscles may have a relationship with the mutation location of collagen VI gene.

Clinical and Brain Magnetic Resonance Imaging Features in a Cohort of Chinese Patients with Kearns-Sayre Syndrome.

BACKGROUND: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients. METHODS: Nineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed. RESULTS: The mean age of onset was 9.6 ± 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3-72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology. CONCLUSIONS: The clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions.

Determination of oxygen extraction fraction using magnetic resonance imaging in canine models with internal carotid artery occlusion.

Perfusion of the penumbra tissue below the flow threshold for functional disturbance but above that for the maintenance of morphological integrity is the target for therapy in acute ischaemic stroke. The measurement of the oxygen extraction fraction (OEF) may provide a direct assessment of tissue viability, so that irreversible tissue damage and penumbra can be reliably identified. By using an asymmetric spin echo single-shot echo planar imaging (ASE-SSEPI) sequence, the quantitative OEF was obtained in the ischaemic brain tissues of canine models with internal carotid artery occlusion. TTC staining, which delineated the regions of infarct and penumbra, was used for defining the corresponding regions on OEF maps. The threshold of the OEF to discriminate the infarct cores and penumbral tissues was then determined according to the OEF values at different times. With repeated-measures ANOVA, the OEF of the infarcted regions was found to be time dependent. An OEF greater than 0.48 best predicted cortical infarction at 1.5 hr, with an area under the receiving operating characteristic curve of 0.968, a sensitivity of 97.5%, and a specificity of 92.5%. Our results may be helpful in the evaluation of tissue viability during stroke events.

Evaluation of bilateral cingulum with tractography in patients with Alzheimer's disease.

A fiber-tracking algorithm was used to extract fractional anisotropy of bilateral cingulum bundles in patients with probable Alzheimer's disease and normal aging controls. In addition, their hippocampal volumes were measured manually. Relative to normal controls, Alzheimer's disease patients showed a significant reduction of fractional anisotropy and hippocampal volumes. Significant correlation was observed between fractional anisotropy values and volumes of hippocampi and mini-mental state examination scores. This study suggests that lower anisotropy of cingulum bundles is associated with cognitive dysfunction and atrophy of the limbic system.

Patterns of brain activation in patients with mild Alzheimer's disease during performance of subtraction: an fMRI study.

We performed a functional MRI (fMRI) study to compare the difference of activation between healthy aged people and patients with mild Alzheimer's disease (AD) during performance of subtraction. Nine patients with mild AD and nine healthy aged volunteers were recruited in this study. The analysis of fMRI data revealed that brain activation is decreased in several regions in AD patients in comparison with healthy participants. But in the right inferior prefrontal lobe, activation is greater in patients than in the controls. We believe that our findings will help the understanding mechanism of neuronal activity in AD.

[Clinical and genetic analysis of a family with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation].

OBJECTIVE: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare autosomal recessive disease. Affected individuals are invariably compound heterozygous for two mutations in DARS2. No reports of LBSL patients have been published in the mainland of China. The aim of this study was to explore the clinical and genetic features of a family with LBSL, which may contribute to definite diagnosis, genetic counseling and prenatal diagnosis of this rare disease in China. METHODS: Clinical data of the proband and other family members as well as DNA samples were collected. Clinical features including symptoms, signs and cranial MRI were analyzed. All 17 exons and exon-intron boundaries of DARS2 gene were amplified with polymerase chain reaction (PCR) and directly sequenced for genomic DNA. The mutation was proved by DNA restriction enzyme digestion of PCR-amplified fragments. RESULTS: (1) The clinical features of patient with LBSL included slowly progressive cerebellar ataxia and spasticity, the neurologic dysfunction involving the legs more than the arms, and with characteristic abnormalities observed on brain and spinal cord MRI. (2) Two mutations were identified, one was a novel missense mutation [c.665 G > A(p.Gly222Asp)] in DARS2 gene exon 8, the other (c.228-16 C > G) was in DARS2 gene intron 3. CONCLUSION: This is the first report on LBSL patient and DARS2 mutation in China. p.Gly222Asp mutation is a novel mutation not reported around the world yet.