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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.

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

Objective: To identify the magnetic resonance (MR) features of a group of pediatric patients with Leigh syndrome (LS) caused by SURF1 gene 604G→C mutation. Materials and Methods: Eight cases with definite diagnosis of SURF1 gene 604G→C mutation in our hospital were reviewed. Most cases presented typical symptoms in their infancy or childhood, with psychomotor regression, hypotonia, or eye movement disturbances. They all underwent cranial MR examinations after the onset. Their brain images were reviewed by an experienced neuroradiologist to determine the abnormalities. Results: The data of our group showed heterogeneous neuroradiological findings: involvement of the brain stem and subthalamic nuclei was found in only three cases; basal ganglia abnormalities were detected in two cases, whereas demyelination was demonstrated in four cases; and brain atrophy existed invariably in the group. Conclusion: The MR presentation in LS patients with SURF1 gene 604G→C mutation is variable. Maybe it is not appropriate to correlate a specific gene mutation with a homogenous radiological pattern.

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.

This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191TC 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. 10191TC mutation in ND3 gene of mitochondria was identified in the boy. 10191TC 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 10191TC 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.

To delineate the phenotype and genotype characteristics in 12 Chinese children with Alexander disease (AD), which is helpful for the molecular diagnosis and genetic counseling in China.Clinical diagnosis of AD was based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA sequencing.The 12 cases of AD were clinically diagnosed. Age of first visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints: developmental delay in 3, recurrent seizures in 7, unable to walk after falling in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age-matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according to Gross motor functional classification system (GMFCS) was performed, with GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in 8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67 years, their motor and cognitive function remained stable. Episodic aggravations provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous missense mutations of GFAP were detected in 12 patients. All mutations were de novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot mutations, which was consistent with previous reports. Mutations were located in exon 1 in 8 cases.The phenotype in these patients is characterized by slower progression compared with reports from other population and high incidence of seizures. And episodic aggravations provoked by fever or falling were more common. The genotype characteristics are consistent with previous reports. The results of this research expanded the number of patients with Alexander disease found to have GFAP coding mutations in China.

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.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.(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 GA(p.Gly222Asp)] in DARS2 gene exon 8, the other (c.228-16 CG) was in DARS2 gene intron 3.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.

To study the clinical and enzymological characteristics of the children with mitochondrial respiratory chain complex III deficiency.The clinical manifestations of five patients (3 males, 2 females) were summarized. Spectrophotometric assay was used for the analysis of respiratory chain complex I to V enzyme activity in peripheral blood leukocytes, after obtaining venous blood.(1) Five patients were hospitalized at the age of 1 month to 15 years. Three patients had Leigh syndrome with progressive motor developmental delay or regression and weakness. One had severe liver damage and intrahepatic cholestasis. One presented muscle weakness. (2) Deficient complex I + III activity was identified in five patients. Their complex I + III activities in peripheral blood leukocytes were 3.0 to 14.2 nmol/min per mg mitochondrial protein (control: 84.4 ± 28.5 nmol/min per mg mitochondrial protein). The ratio of complex I + III to citrate synthase decreased to 3.5 to 22.9% (normal control 66.1 ± 14.7%). The activities of complex III decreased to 10.4 to 49.3% of the lowest control value, while complex I, II, IV and V activities were normal. The results supported the diagnosis of isolated respiratory chain complex III deficiency.Complex III deficiency is a kind of disorder of energy metabolism with various manifestations. The complex I + III activities and the ratio of complex I + III to citrate synthase were lower than those of the control. The activities of complex I, II, IV and V were normal.

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.

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 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 13513GA 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. 13513GA 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. 13513GA mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.

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.

To analyze and review the characteristics of leukoencephalopathy with vanishing white matter (VWM).The clinical features including clinical manifestations, neurologic signs, cranial MRI and laboratory tests in 9 patients with the diagnosis of VWM were analyzed and the characteristics of the disease were reviewed.8 cases had symptoms involving central nervous system, 1 case only showed abnormal cranial MRI findings. The onset of the disease occurred between 6 months to 3 years of age. Family history was positive in 5 cases. Almost all cases had normal psychomotor development before the onset of the disease. The initial symptom was usually movement disorder with predominant involvement of lower limbs. The onset or deterioration of the disease was followed by respiratory tract infection in 6 cases and minor head trauma preexisted in 3 cases. The course of the disease was progressive in 7 cases and there was episodic deterioration in 4 cases. Mental abilities were relatively better preserved. Head circumference was normal in 7 cases. Positive upper motor unit signs were found in 8 cases and ataxia in 4 cases. Bilateral optic nerve atrophy was found in 3 cases. Cranial MRI indicated diffuse and symmetrical involvement of deep white matter which showed long T(1) and T(2) signal. Subcortical white matter was also involved with predominance in frontal and parietal lobes. Flair image showed symmetrical high signal intensity in cerebral white matter with low signal intensity similar to that of CSF in partial area or low signal in most area of white matter with only meshwork of higher signal preserved. The results of all the laboratory tests including the enzyme and biochemical test specific for some well-known leukoencephalopathy were normal.The clinical features of VWM include: 1. Initial symptom is usually movement disorder; 2. Movement disorder is more prominent compared to mental retardation; 3. Cranial MRI shows symmetrical abnormal T(1) and T(2) signal in deep white matter with signs of vanishing white matter. Exclusion of other hereditary and acquired leukoencephalopathy is necessary for diagnosis. Final diagnosis should be made on the basis of genetic evidence.

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· (100 g) -1 ·min -1 and (43±10) ml·(100 g) -1 ·min -1 in the gray and white matter respectively. There was significant main effect of location (t=-12.5, P

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.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.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.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.

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.

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.

X-linked adrenoleukodystrophy (ALD) is a genetically determined disorder that involves the nervous system white matter, axons, adrenal cortex and testes. The typical clinical manifestations are progressive psychomotor regression, vision and/or auditory impairment and adrenal insufficiency. The clinical manifestation, biochemical change and genetic counseling work of X-linked ALD were analyzed.The clinical features of 29 cases with ALD were summarized and analyzed, including symptoms and signs, measurement of blood very long chain fatty acids (VLCFA), adrenal function, cranial magnetic resonance imaging (MRI) and pedigree investigation.Among these 29 cases, the clinical phenotype could be classified into childhood cerebral (22 cases), adolescent cerebral (4 cases), adrenomyeloneuropathic (1 case), Addison's disease (1 case) and asymptomatic or presymptomatic (1 case) types. Nine of them had positive family history. Pedigree investigation was consistent with typical sex-linked recessive inheritance. There were 45 ALD patients in these 29 pedigrees. The neurological manifestations varied among members of the same family. Nine cases died during follow up. The causes of death were central respiratory failure or other complications of ALD and so on. Laboratory tests demonstrated abnormally high plasma levels of VLCFA in ALD patients; MRI demonstrated symmetric butterfly-like low T(1) and high T(2) signals in the parieto-occipital white matter. The impairment in the splenium of corpus callosum made the bilateral lesion region converge into one. It could progress anteriorly and injure the bilateral posterior limb of internal capsule and the temporal lobe, and could injure the brainstem inferiorly. Following intravenous injection of contrast material, thin stripe of lacelike enhancement could be observed.The atypical initial symptom of ALD was seizures. The MRI showed abnormal signal in the cerebellar white matter. This disease can influence the normal development of children, this was more pronounced in the childhood cerebral ALD type. It tended to progress rapidly with dementia, vegetative state or death. Since antenatal diagnostic method is available now, emphasis should be made on the antenatal examination in order to make an early diagnosis and abort pregnancy if necessary.