Human leg neuromuscular diseases: P-31 MR spectroscopy

Phosphorus-31 magnetic resonance (MR) spectra of leg muscles in patients with the neuromuscular diseases Duchenne dystrophy, myotonic dystrophy, postpoliomyelitis, Werdnig-Hoffmann disease, and pedal dystonia were recorded. Ratios of beta-adenosine triphosphate (ATP), inorganic phosphate (Pi), alpha-glycerophosphorylcholine (GPC), and phosphomonoesters to phosphocreatine (PCr) were calculated from peak integrals and compared with normal muscle ratios. In all diseases studied, beta-ATP/PCr and Pi/PCr values showed an increase from normal values. The extent of increase in beta-ATP/PCr was related to the clinical severity of the disease, suggesting that this could be a useful noninvasive means of monitoring effectiveness of therapy for neuromuscular disorders. In myotonic dystrophy and Werdnig-Hoffmann disease, GPC/PCr values increased greatly. The intracellular pH in Duchenne and postpoliomyelitis muscles was slightly elevated compared with that in normal muscles. Hydrogen-1 MR images of muscles showed fat infiltration in all patients, more in weaker muscles and less in stronger muscles.     

Evaluation of brain in myotonic dystrophy using diffusion tensor MR imaging

In many cases of myotonic dystrophy, high-intensity areas are seen in the cerebral white matter on T2-weighted imaging. Brain MRI was performed in 15 patients with myotonic dystrophy using diffusion tensor imaging, which is sensitive to the detailed structure of white matter, and the results were compared with those of normal controls. FA (anisotropic diffusion) values in the cerebral white matter of myotonic dystrophy patients were significantly lower than those of normal controls (p< 0.01), even if the hyperintense lesion was not seen on T2-weighted imaging. Values of trace (isotropic diffusion) in myotonic dystrophy patients were significantly higher than those of normal controls (p< 0.05), except in the posterior limb of the internal capsule. Diffusion tensor imaging could detect pathological change of the cerebral white matter in myotonic dystrophy patients, and may be useful for quantification and detection of subtle pathological change.     

In vivo 23Na NMR studies of myotonic dystrophy

Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology leading to muscle malfunction and damage is not well understood. ²³Na NMR spectroscopy was applied here for an in vivo comparative study of the calf muscles of 7 myotonic dystrophy patients at various stages of the disease and 11 healthy volunteers. Both the total sodium content, expressed as the ratio of the ²³Na and ¹H water signals, and the fast transverse relaxation time, T₂₁, determined from the triple quantum-filtered spectra, increased in correlation with the severity of the disease. The results demonstrate that ²³Na NMR enables the quantitation of myotonic dystrophy progression.     

T2 relaxometry of brain in myotonic dystrophy

We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease. Received: 31 May 2000 Accepted: 27 July 2000     

Quantitative assessment of the total myocardial uptake ratio of 123I-BMIPP by using the Ishii-MacIntyre method is useful for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy

We evaluated the usefulness of the total myocardial uptake ratio (TMUR) of 15-(p-[123I]iodophenyl)-3(R,S)-methyl-pentadecanoic acid (123I-BMIPP) for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy. Six patients with mitochondrial encephalomyopathy, four with myotonic dystrophy, and 10 control subjects were studied. Quantitative assessment of 123I-BMIPP dynamic myocardial imaging was performed, and the TMUR of 123I-BMIPP was calculated according to the Ishii-MacIntyre method. Then, the TMUR was compared in the 10 patients and 10 healthy controls, and all patients were followed for 56.1+/-22.1 months to evaluate cardiac complications. TMUR in patients (2.69+/-0.64) was significantly (P =0.01) lower than that in controls (3.28+/-0.25). Three patients in whom the TMUR value was above 3.00 had no cardiac complications. On the other hand, all patients in whom TMUR was below 3.00 had some kind of cardiac complication during the follow-up period. Two patients showed progressive conduction abnormality and underwent pacemaker implantation, one patient had sick sinus syndrome and underwent pacemaker implantation, another patient showed non-sustained ventricular tachycardia and paroxysmal atrial fibrillation, and four of seven patients, including one with a pacemaker, showed an increased cardiothoracic ratio value over 50%. In conclusion, measurement of the TMUR by the Ishii-MacIntyre method is useful for evaluating the development of cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy.     

QRS prolongation in myotonic muscular dystrophy and diffuse fibrosis on cardiac magnetic resonance

Current noninvasive surrogates of cardiac involvement in myotonic muscular dystrophy have low positive predictive value for sudden death. We hypothesized that the cardiac MR signal‐to‐noise ratio variance (SNRV) is a surrogate of the spatial heterogeneity of myocardial fibrosis and correlates with electrocardiography changes in myotonic muscular dystrophy. The SNRV for contrast enhanced cardiac MR images was calculated over the entire left ventricle in 43 patients with myotonic muscular dystrophy. All patients underwent standard electrocardiography, and a subset of 23 patients underwent signal averaged electrocardiography. After correcting for body mass index, age, and ejection fraction, SNRV was predictive of QRS duration on standard electrocardiography (1.35‐msec increased QRS duration/unit increase in SNRV, P < 0.001). SNRV was also predictive of the low‐amplitude late‐potential duration (1.49‐msec increased low‐amplitude late‐potential duration/unit increase in SNRV, P < 0.001). Ten‐fold cross‐validation yielded an area under the receiver operating characteristic curve of 0.87 for the predictive value of SNRV for QRS duration greater than 120 msec. The SNRV of the left ventricle is associated with QRS prolongation, likely due to late depolarization of tissue within islands of patchy fibrosis. The association of SNRV with future clinical events warrants further study. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Myotonic dystrophy (Steinert''s disease) in the neonate

Radiological abnormalities of the ribs are reported in 5 newborn infants with myotonic dystrophy. In all 5, the ribs appeared very thin, in contrast to the normal appearance of the rest of the skeleton. This slenderness, which is important for diagnosis and prognosis, seems to be caused by hypotonia of the intercostal muscles. However, it is not pathognomonic of myotonic dystropy, for it can be observed in other myopathies.     

Right ventricular MR abnormalities in myotonic dystrophy and relationship with intracardiac electrophysiologic test findings: initial results

PURPOSE: To prospectively determine whether a relationship exists between magnetic resonance (MR) imaging abnormalities of the right ventricle (RV) and intracardiac electrophysiologic (EP) test results in patients with myotonic dystrophy. MATERIALS AND METHODS: Conventional T1-weighted single-shot black-blood fast spin-echo and gradient-echo MR imaging of the heart was prospectively performed in 32 patients with myotonic dystrophy who required EP testing. Patients were divided into two groups according to EP test results: (a) inducible (n = 15), indicating inducible ventricular tachyarrhythmias, and (b) noninducible (n = 17). Morphologic and functional MR data were analyzed by two independent investigators. Nonparametric statistical methods and kappa statistics were used. RESULTS: No morphologic or functional abnormalities of the RV wall were observed in noninducible patients. Increased signal intensity of the RV wall, indicative of fatty replacement, was identified in 13 inducible patients. Myocardial thinning of the RV was observed in six inducible patients. An overlap of morphologically abnormal areas and areas of hypo- or dyskinesis were present in 11 inducible patients. RV outflow tract diameter was larger and RV ejection fraction was smaller in inducible patients than in noninducible patients, although differences were not significant. Interobserver agreement for MR findings was good (increased signal intensity: kappa = 0.87, P >.30 [pairwise Wilcoxon signed rank test]; myocardial thinning: kappa = 0.87, P >.30; hypo- or dyskinesis: kappa = 1.00, P >.99). There was a strong relationship between MR abnormalities and inducibility during EP testing (increased signal intensity, P <.001; myocardial thinning, P <.01; hypo- or dyskinesis, P <.01). CONCLUSION: The relationship between MR morphologic and functional RV abnormalities and EP testing suggests potential for the use of MR imaging as a noninvasive method to estimate the individual risk of arrhythmia in patients with myotonic dystrophy.     

Magnetic resonance imaging findings of basal cell adenoma in Curschmann-Steinert myotonic dystrophy

Myotonic dystrophy Curschmann Steinert is a common hereditary disorder that in some cases can be combined with cutaneous tumors, which is an association that is rarely described in the literature. We present the magnetic resonance imaging in the unusual combination of a patient with known myotonic dystrophy and recurrent basal cell tumor.     

The clinical and genetic correlates of MRI findings in myotonic dystrophy

Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multisystem disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68 %), subcortical white matter lesions (65 %), wide Virchow-Robin spaces (38 %) and thickening of the skull (35 %). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38 % and the calf in 44 %. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits. Received: 12 April 1995 Accepted: 25 August 1995     

MRI在进行性肌营养不良中的应用价值

目的探讨进行性肌营养不良(progressive muscular dystrophy,PMD)的骨骼肌MRI表现与临床的相关性及其应用价值。资料与方法对22例经临床表现、血清肌酸激酶(CPK)、肌电图检查及开放式骨骼肌活检、组织及免疫病理学证实的PMD患者的临床及影像资料进行回顾性分析。结果各型肌病MRI受累肌肉分布特征为:杜兴型和贝克型为大腿前部肌群;肢带型2B型为大腿后部肌群;远端型中Welander型为大腿后部肌群及小腿前群、外侧群肌肉;Nonaka型为小腿前群、外侧群肌肉;Miyoshi型为小腿后部肌群;先天性为大、小腿后部肌群;强直性为大、小腿前、后肌群。MRI上的病变程度与病程无一致性关系。除假肥大型无肌肉水肿表现外,其余类型均有不同程度的肌肉水肿。结论 MRI表现提示不同的肌病类型有特定的分布,有助于临床鉴别某些类型的肌病。利用对脂肪沉积和水肿敏感的MRI序列,有助于理解肌病的病理过程,协助临床检查监测对治疗的反应。     

MRI of the brain in muscle-eye-brain (MEB) disease

Muscle-eye-brain (MEB) disease belongs to the spectrum of rare congenital syndromes with migration disorders of the brain and muscular dystrophy, along with the Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy. Their features overlap, and differential diagnosis presents some difficulties. We examined the brain of 10 patients with MEB using highfield MRI and found a uniform pattern consisting of a pachygyria-type cortical migration disorder, septal and corpus callosum defects and severe hypoplasia of the pons in 7 of them.     

Subperiosteal new bone and callus formations in neonates with femoral shaft fracture at birth

To compare the timing of subperiosteal new bone formation (SPNBF) and callus formation in femoral shaft fractures that occurred at birth between neonates with and without an underlying disease, we retrospectively evaluated the radiographs of 12 neonates with femoral fractures on birth day. Seven had no underlying disease, 3 had osteogenesis imperfecta, 1 had myotonic dystrophy, and 1 had arthrogryposis. We evaluated the timing of initial SPNBF/soft callus/hard callus formation. In neonates without an underlying disease, SPNBF and callus formation were not detected by day 6 on radiographs; SPNBF/soft callus/hard callus formation was first observed at day 14.29 ± 5.35/15.85 ± 4.49/21.43 ± 5.41, respectively (range 9–23/10–23/16–32). The three neonates with osteogenesis imperfecta had SPNBF/soft callus/hard callus formation on day 0/0/0, which was significantly earlier than in neonates without an underlying disease (all P = 0.017). In the neonate with myotonic dystrophy, SPNBF/soft callus/hard callus formation was first seen by day 14/14/14 and was first seen by day 20/43/68 in the neonate with arthrogryposis. In our restricted cohort, all neonates with femoral shaft fractures from birth trauma without an underlying disease showed SPNBF and soft callus formation by day 23. If SPNBF or callus formation is detected within 6 days, an underlying disease (e.g., osteogenesis imperfecta) may be considered. If these are not detected by day 23, injury after birth or other underlying diseases may be considered.     

The fluid-attenuated inversion-recovery pulse sequence in assessment of central nervous system involvement in myotonic dystrophy

We compared the fluid-attenuated inversion recovery (FLAIR) sequence with conventional spin-echo (SE) imaging for detection of involvement of the central nervous system in five patients with myotonic dystrophy (MD). The diagnosis was made based on clinical features and DNA analysis. All patients showed abnormal high-intensity lesions in the white matter on T2-weighted images, although these were more clearly visible using FLAIR. Received: 3 January 1997 Accepted: 18 June 1997     

Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy

The diagnostic potential of volume-selective proton magnetic resonance (MR) spectroscopy in vivo was evaluated in 20 children and young adults with various neurodegenerative brain disorders. All patients were examined with MR spectroscopy in conjunction with MR imaging of the brain on a whole-body imager at 1.5 T. Comparison of spectra in our patients with those of children with normal myelination (prominent signals from N-acetylaspartate [NAA], creatine/phosphocreatine, and choline) revealed a marked decrease of NAA in 12 of 17 patients with focal or generalized demyelination. In patients with Canavan disease, NAA signal intensity was markedly increased, but no choline signal was found. Increased signal intensity from lactate occurred in patients with Leigh disease, neuroaxonal dystrophy, Schilder disease, and Cockayne disease, which indicated a disturbed energy metabolism in the examined region. These results demonstrate that proton MR spectroscopy can be applied in a clinical environment to facilitate diagnosis of hereditary and acquired brain disorders in children.     

MR imaging findings in children with merosin-deficient congenital muscular dystrophy

BACKGROUND AND PURPOSE: Our purpose was to determine the brain MR imaging characteristics of merosin-deficient congenital muscular dystrophy in children. METHODS: We reviewed the MR imaging findings of the brain in three children with known merosin-deficient congenital muscular dystrophy to determine the presence of any cerebral or cerebellar abnormalities of development or abnormalities of the white matter. RESULTS: In all three patients, there was normal formation of the cerebrum, the cerebellum, and no evidence of neuronal migration anomalies. All three patients had abnormal white matter in the cerebrum, with sparing of the corpus callosum, internal capsule, cerebellum, and brain stem. CONCLUSION: MR imaging of the brain in children with merosin-deficient congenital muscular dystrophy reveals a consistent pattern of white matter abnormality. We postulate that disruption of the blood-brain barrier associated with merosin deficiency leads to increased water content, resulting in abnormal white matter signal intensity.     

Cranial MRI findings in myotonic dystrophy

MRI was performed in 13 patients with the adult form of myotonic dystrophy (MD) and compared with that of sex- and age-matched normal controls. There was some cerebral atrophy in the patients and marked thickening of the skull in three of them, associated with ossification of the falx cerebri in two. We found high-signal areas on T 2-weighted images in the white matter in 9 (70 %) of the patients; five showed high-signal areas in the subcortical white matter of the temporal lobes. These findings were associated with intellectual impairment in only one patient, who had a history of a difficult birth and temporal lobe epilepsy. Received: 31 October 1995 Accepted: 5 March 1996     

Diffusion tensor imaging of cerebral white matter in patients with myotonic dystrophy

PURPOSE: To determine whether myotonic dystrophy (MyD) patients have diffusion tensor abnormalities suggestive of microstructural changes in normal-appearing white matter (NAWM). MATERIAL AND METHODS: Conventional and diffusion tensor magnetic resonance images of the brain were obtained in 19 MyD patients and 19 age-matched normal control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in white matter lesions (WMLs) and NAWM in MyD patients and in the white matter of normal control subjects. Differences between WML and NAWM values and between MyD patient and control subject values were analyzed statistically. RESULTS: Significantly lower FA and higher MD values were found in all regions of interest in the NAWM of MyD patients than in the white matter of control subjects (P<0.01), as well as significantly lower FA and higher MD values in WMLs than in NAWM of MyD patients (P < 0.05). There was no significant correlation of mean FA or MD values in NAWM with patient age, age at onset, or duration of illness (P>0.1). CONCLUSION: Diffusion tensor imaging analysis suggests the presence of diffuse microstructural changes in NAWM of MyD patients that may play an important role in the development of disability.     

Imaging techniques in myotonic dystrophy. A comparative study of ultrasound, computed tomography and magnetic resonance imaging of skeletal muscles.

Limb and trunk muscles of 57 patients with the juvenile or adult form of myotonic dystrophy were studied by imaging techniques (ultrasound, computed tomography, magnetic resonance imaging). Typical findings were atrophy of the tibialis anterior and triceps brachii muscles and fatty degeneration of the vastus intermedius, sartorius, tibialis anterior and soleus muscles as well as of medial head of the gastrocnemius muscle. Magnetic resonance imaging was the most sensitive technique in depicting mesenchymal muscle alterations, followed by computed tomography and ultrasound. The data support that imaging is more sensitive in detecting the myopathy than measurement of the creatine kinase activity.