Patient with multiple acyl-CoA dehydrogenation deficiency disease and FLAD1 mutations benefits from riboflavin therapy.

Multiple acyl-CoA dehydrogenation deficiency is genetically heterogenous metabolic disease with mutations in genes involved in electron transfer to the mitochondrial respiratory chain. Disease symptoms vary from severe neonatal form to late-onset presentation with metabolic acidosis, lethargy, vomiting, muscle pain and weakness. Riboflavin therapy has been shown to ameliorate diseases symptoms in some of these patients. Recently, mutations in FAD synthase have been described to cause multiple acyl-CoA dehydrogenation deficiency. We describe here the effect of riboflavin supplementation therapy in a previously reported adult patient with multiple acyl-CoA dehydrogenation deficiency having compound heterozygous gene variations in FLAD1 (MIM: 610595) encoding FAD synthase. We present thorough clinical history including laboratory investigations, muscle MRI, muscle biopsy and spiroergometric analyses comprising of a follow-up of 20 years. Our data suggest that patients with adult-onset multiple acyl-CoA dehydrogenation deficiency with FLAD1 gene mutations also benefit from long-term riboflavin therapy.

Episodic muscle pain, stiffness, and weakness associated with tubular aggregates and myoedema.

We report a 28-year-old man who suffered from episodic muscle pain, stiffness and weakness. His serum creatine kinase (CK) levels were found to be elevated. He presented with slight proximal muscle weakness and calf hypertrophy. Muscle biopsy revealed fiber size variation and tubular aggregates (TA). Muscle magnetic resonance imaging showed areas of edema. Other muscle pathologies known to be associated with TAs or myoedema were ruled out.

Multidetector computed tomography in acute knee injuries: assessment of cruciate ligaments with magnetic resonance imaging correlation.

PURPOSE: To evaluate whether non-contrast multidetector computed tomography (MDCT) for suspected acute knee fractures can also be used to evaluate cruciate ligament pathology. MATERIAL AND METHODS: A total of 42 patients (17-65 years) underwent four-section MDCT. The images were independently evaluated at clinical workstations by four radiologists. They assessed the integrity (normal or torn) and the best slice direction (axial, sagittal, or coronal) for visualization of the cruciate ligaments. Magnetic resonance imaging (MRI), performed within 4 weeks (mean 6 days) in relation to MDCT, was considered the gold standard. RESULTS: Ligament integrity at MDCT: the mean interobserver proportion of agreement for a normal anterior cruciate ligament (ACL) was 0.73, for a torn ACL 0.41, for a normal posterior cruciate ligament (PCL) 0.96, and for a torn PCL 0.54. Interobserver variation for ACL was significant (P = 0.0136-0.0260), but insignificant for PCL (P = 0.3389-0.7212). Intra-observer variation was insignificant. Visualization was best in the axial and sagittal direction for ACL and PCL, respectively. At MRI, 29 normal, one partially, and 12 completely torn ACLs, and 37 normal, four partially and one completely torn PCL were found. CONCLUSION: MDCT can detect an intact ACL and PCL with good specificity, accuracy, and negative predictive value. The assessment of torn ligaments is unreliable.

Disc degeneration of the lumbar spine in relation to overweight.

OBJECTIVE: To study the association between overweight and lumbar disc degeneration. DESIGN: Population-based 4-y follow-up magnetic resonance imaging (MRI) study. SUBJECTS: The subjects were 129 working middle-aged men selected to the baseline magnetic resonance imaging (MRI) study from a cohort of 1832 men representing three occupations: machine drivers, construction carpenters, and office workers. The selection was based on the paticipants' age (40-45 y) and place of residence. MR images of the lumbar spines were obtained at baseline and at 4-y follow-up. MEASUREMENTS: Signal intensity of the nucleus pulposus of the discs L2/L3-L4/L5 was visually assessed by two readers using the adjacent cerebrospinal fluid as an intensity reference. The weight (at age 25 and 40-45 y) and height of the subjects, history of car driving, smoking, and back injuries were assessed by questionnaire. RESULTS: Multiple regression analyses allowing for occupation, history of car driving, smoking, and back injuries showed that persistent overweight (body mass index (BMI) > or =25 kg/m(2) at both ages) associated strongly with an increased risk of the number of lumbar discs with decreased signal intensity of nucleus pulposus at follow-up, adjusted odds ratio (OR) being 4.3 (95% confidence intervals (95% CIs) 1.3-14.3). Overweight at young age (risk ratio (RR) 3.8; 95% CI 1.4-10.4) was a stronger predictor of an increase in the number of degenerated discs during follow-up than overweight in middle age (RR 1.3; 95% CI 0.7-2.7). CONCLUSIONS: The study provides evidence that the BMI above 25 kg/m(2) increases the risk of lumbar disc degeneration. Overweight at young age seems to be particularly detrimental.

Muscle magnetic resonance imaging shows distinct diagnostic patterns in Welander and tibial muscular dystrophy.

OBJECTIVES: This is a report on a retrospective muscle magnetic resonance imaging (MRI) study on 11 patients affected by Welander distal myopathy (WDM) and 22 patients with tibial muscular dystrophy (TMD) carried out in order to define the pattern and characteristics of muscle involvement. RESULTS: WDM patients showed involvement of gastrocnemius, soleus, tibial anterior (TA) and extensor digitorum longus (EDL), as well as hamstrings and hip adductor muscles. TMD patients showed involvement of the TA and EDL muscles, and in some patients also hamstring and posterior compartment muscles of the legs. Some patients showed asymmetry of muscle involvement. CONCLUSION: We conclude that muscle MRI examination proved to be very useful in the determination of the exact pattern of muscle involvement in WDM and TMD. Clinical testing using the Medical Research Council scale is not sensitive enough to establish the pattern of muscle involvement in focal muscle diseases.

Low back pain in relation to lumbar disc degeneration.

STUDY DESIGN: Cross-sectional magnetic resonance imaging (MRI) study. OBJECTIVES: To study the relation of low back pain (LBP) to disc degeneration in the lumbar spine. BACKGROUND DATA: Controversy still prevails about the relationship between disc degeneration and LBP. Classification of disc degeneration and symptoms varies, hampering comparison of study results. METHODS: Subjects comprised 164 men aged 40-45 years-53 machine drivers, 51 construction carpenters, and 60 office workers. The data of different types of LBP, individual characteristics, and lifestyle factors were obtained from a questionnaire and a structured interview. Degeneration of discs L2/L3-L5/S1 (dark nucleus pulposus and posterior and anterior bulge) was assessed with MRI. RESULTS: An increased risk of LBP (including all types) was found in relation to all signs of disc degeneration. An increased risk of sciatic pain was found in relation to posterior bulges, but local LBP was not related to disc degeneration. The risks of LBP and sciatic pain were strongly affected by occupation. CONCLUSIONS: Low back pain is associated with signs of disc degeneration and sciatic pain with posterior disc bulges. Low back pain is strongly associated with occupation.

A shielded Overhauser marker for MR tracking of interventional devices.

Improvements to an active MR tracking technique are described. Real-time position monitoring of interventional procedures can be realized by incorporating a small marker that emits an NMR signal into the tip of an interventional device, and the marker's emitted NMR signal is enhanced by use of the Overhauser phenomenon. A significant advance over prior designs has achieved by making the marker have a cylindrical shape and by confining the saturation energy to the marker's interior. The performance of the improved active marker was verified in the laboratory and in vitro. The experiments demonstrated that the marker was visible in MR images when inserted in different excised tissues, and even in air, with positive contrast and with various imaging sequences. The tissue magnetization was minimally perturbed, and the marker emitted a variable but enhanced signal in all orientations in the magnetic field. The marker can potentially be used to mark locations on the body for frameless stereotaxy or to identify inserted devices.

High-accuracy MR tracking of interventional devices: the Overhauser marker enhancement (OMEN) technique.

A new technique for visualization of interventional devices in magnetic resonance imaging is presented. Determination of the position of an invasive device is made possible by incorporating into the device a small marker that emits the NMR signal. This signal is enhanced by the use of the Overhauser phenomenon. This technique differs from the earlier reported techniques for marking interventional instruments in the sense that the contrast between the marker and tissue is not based on different relaxation rates, but on NMR signal enhancement. A prototype marker was constructed and inserted into an inductively fed loop-gap resonator that couples saturation energy with the marker. Circuit analogies are presented that model the Overhauser phenomenon and the coupling circuit. In vitro experiments demonstrated that the marker is visible in MR images up to a slice thickness of 50 mm when inserted in excised animal liver and fat tissues.

Lumbar disc degeneration in relation to occupation.

OBJECTIVES: The aim was to study risk factors of lumbar disc degeneration demonstrable with magnetic resonance imaging (MRI) with special emphasis on occupational load and back accidents. METHODS: The subjects in this cross-sectional study were 53 machine drivers, 51 construction carpenters, and 60 municipal office workers aged 40-45 years. Data on possible risk factors were available from current structured questionnaires and for 4 and 7 years in retrospect. The prevalence of lumbar disc degeneration L2/L3-L5/S1 was determined with MRI. RESULTS: An increased risk was found for posterior disc bulges among the carpenters and for anterior disc bulges among the machine drivers, but decreased signal intensity was not related to occupation. Car driving was also associated with anterior disc bulges. All signs of disc degeneration were related to a history of back accidents. Disc degeneration was not related to body height, overweight, smoking, or the frequency of physical exercise. CONCLUSIONS: Occupational load affects the risk of disc degeneration of the lumbar spine. Accidental back injuries and motor vehicle driving are associated with an increased risk of disc degeneration. Anterior and posterior disc bulges seem to be related to different types of physical loads.

Antimyosin scintigraphy compared with magnetic resonance imaging in inflammatory myopathies.

OBJECTIVE: To compare indium In 111 altumomab pentetate-labeled antimyosin scintigraphy with magnetic resonance imaging (MRI) in the diagnosis and follow-up of patients with myositis. DESIGN AND METHODS: Sixteen patients with polymyositis and 1 patient with dermatomyositis, all verified with biopsy samples, were examined during diagnostic evaluation with antimyosin antibody scintigraphy and low-field MRI of the thighs and calves using T1- and T2-weighted sequences. Both examinations were repeated 6 to 22 months after therapeutic intervention with antiinflammatory drugs. The performance of the 2 methods for the assessment of the severity of muscle inflammation was evaluated using comparison with clinical examination and the serum creatine kinase level. RESULTS: At diagnosis all patients had increased uptake of antimyosin antibody in the thighs and/or calves. In T2-weighted MRI images, increased signal intensity changes reflecting intramuscular edema and inflammation were seen in all patients in at least 1 muscle group in the thighs or calves. After anti-inflammatory drug therapy, the mean uptake of antibody and the mean signal intensity changes in T2-weighted MRI had decreased. However, in T1-weighted MRI the signal intensity changes reflecting intramuscular fatty degeneration were more pronounced in the follow-up study. The level of serum creatine kinase had decreased markedly by the second examination except in 1 patient who also had more accumulation of antibody in the calves after than before treatment. The clinical condition improved in 8 patients and remained unchanged in 9 patients. CONCLUSIONS: Antimyosin scintigraphy and T2-weighted MRI are feasible tools for the detection and follow-up of lesions in patients with myositis. Scintigraphy findings correlate with serum creatine kinase activity and seem to reflect disease activity better than T2-weighted MRI changes, whereas secondary degenerative intramuscular lesions are only detectable using T1-weighted MRI.

Spin lock and magnetization transfer MR imaging of local liver lesions.

The present study was designed to evaluate tissue contrast characteristics obtained with the spin-lock (SL) technique by comparing the results with those generated with a magnetization transfer(MT)-weighted gradient echo [GRE, echo-time (TE)=40 ms] sequence. Twenty-eight patients with hepatic hemangiomas (n=14), or metastatic liver lesions (n=14) were imaged at 0.1 T by using identical imaging parameters. Gradient echo, single-slice off-resonance MT, and multiple-slice SL sequences were obtained. SL and MT-effects were measured from the focal liver lesions and from normal liver parenchyma. In addition, tissue contrast values for the liver lesions were determined. Statistically significant difference between the SL-effects of the hemangiomas and metastases, and also between the MT-effects of the lesions was observed (p < 0.02). Tissue contrast values for the lesions proved to be quite similar between the SL and MT techniques. Our results indicate that at 0.1 T multiple-slice SL imaging provides MT based tissue contrast characteristics in tissues rich in protein with good imaging efficiency and wide anatomical coverage, and with reduced motion and susceptibility artifacts.

Dynamic fast-gradient echo MR imaging of pancreatic tumours.

The purpose of this study was to determine the diagnostic utility of dynamic magnetic resonance imaging (MRI) of the pancreas. Twenty-eight adult patients with known or suspected pancreatic tumours were examined. Pre- and post-gadolinium (GdDTPA-BMA) scans were obtained in combination with an oral negative contrast medium (ferristene) to mark the gastrointestinal tract. In 6 cases a more precise diagnosis could be made by dynamic MRI compared to unenhanced MRI. Surgery could confirm the MR diagnosis based on contrast enhancement in 83% compared to 78% for CT. The results of signal intensity (SI) measurements show that a combination of differences in baseline values before enhancement and the slope of enhancement within the first 20 s is a reliable criterion to distinguish between normal pancreas and hypovascular tumours. These tumours already show lower SI values before as well as lower slopes after early enhancement. Mainly two effects facilitate the final MRI diagnosis: (1) the delineation of the pancreas from the duodenum by the negative contrast medium, and (2) the enhancement pattern of pancreatic tumours by gadolinium-enhanced dynamic MRI compared to normal tissue within the early enhancement after contrast injection.

The value of MRI in early Perthes' disease: an MRI study with a 2-year follow-up.

Eleven hips in nine patients with Perthes' disease were studied by plain radiography at 3-month and MRI at 6-month intervals over a period of 2 years. The aim was to clarify the value of MRI in estimating epiphyseal involvement and in predicting uncoverage of the epiphysis. Signal intensities of the epiphysis and metaphysis were visually evaluated from T1- (T1W) and T2-weighted (T2W) images. The extent of decreased signal intensity (DSI) in the epiphyses was volumetrically calculated from T1W images and then compared with follow-up radiographs. The area of epiphyseal DSI corresponding best with Catterall's classification was seen by MRI 3-8 months after the first symptoms. MRI images obtained earlier usually showed less involvement than the follow-up radiographs. However, two features predicting extensive epiphyseal necrosis were: (1) DSI on both T1W and T2W images covering over two-thirds of the epiphysis and (2) diffuse bone marrow oedema of the femoral neck and metaphysis. When T1W images showed a reappearance of high signal intensity patches in the lateral quarter of the epiphysis, no clinically significant uncoverage was seen during the follow-up. Extensive epiphyseal necrosis can, therefore, sometimes be predicted by MRI even within the first 3 months, but MRI visualises epiphyseal involvement more clearly 3-8 months after the first symptoms.

MRI and CT in blunt renal trauma: an update.

In our experience, MRI is as effective as CT in correctly staging renal injury. The coronal and sagittal slice orientations of MRI are particularly helpful in determining the extent of the renal parenchymal damage. Both methods are accurate in finding perirenal hematomas, assessing the viability of renal fragments, and detecting preexisting renal abnormalities but are relatively inaccurate in visualizing urinary extravasation. Although CT remains the method of choice in radiological staging of renal injury, MRI can complement CT in patients with severe renal injury, preexisting renal abnormality, equivocal CT findings, or when repeated radiological follow-up is required. MRI could replace CT in patients with iodine allergy and be used for initial staging if CT is not available.

MnDPDP as a negative hepatic contrast agent: evaluation of STIR imaging compared with T1-weighted SE and GE techniques.

Our goal was to assess the utility of manganese dipyridoxyl diphosphate (MnDPDP) as a negative hepatic contrast agent in short inversion time IR MRI (STIR). Twenty patients with focal liver lesions (15 with metastatic disease, 5 with hemangiomas) underwent MRI (T1-weighted SE, breath-hold GE, and STIR sequences) before and after infusion of MnDPDP (5 mumol/kg). We then compared the results obtained with each sequence for hepatic parenchymal enhancement, lesion-to-liver contrast-to-noise ratio (C/N) measurements, and the number of focal liver lesions observed in pre- and postcontrast images. Hepatic enhancement values of 25.3 +/- 9.7 and 33.6 +/- 2.7% (mean +/- SEM) were obtained for the T1-weighted SE and GE sequences, respectively. The STIR sequence showed 78.9 +/- 2.1% negative enhancement (decrease of parenchymal signal intensity). Although a significant (p < 0.0001) C/N increase was seen after MnDPDP administration for all sequences, STIR showed the highest increase (149.0 +/- 25.5%) compared with T1-weighted SE (58.5 +/- 12.7%) and GE (83.3 +/- 7.2%) sequences. Similarly, more lesions for all sequences were detected, but again STIR showed the greatest postcontrast increase (29.0%). MnDPDP is an effective hepatic contrast agent. As both the negative hepatic enhancement and the increase in lesion-to-liver C/N were superior with the STIR sequence when compared with the positive enhancement and C/N values produced by the T1-weighted sequences, it should be considered for inclusion in the imaging protocol for patients with focal liver disease.

Interventional MR imaging. Demonstration of the feasibility of the Overhauser marker enhancement (OMEN) technique.

PURPOSE: The poor localization facility of interventional instruments in MR imaging has been one of the major obstacles to the popularization of interventional MR imaging. It has been suggested that the Overhauser enhancement be used to generate markers of small size and high visibility. This article studies the feasibility of a localization marker based on this method. MATERIAL AND METHODS: A small Overhauser marker was constructed on the tip of a coaxial cable and comparative images were taken by a 0.23 T imager with and without electron spin irradiation. RESULTS: During irradiation an enhanced signal intensity from the marker was observed. The signal from the marker also exceeded the signal from a 0.25 mmol MnCl2 reference phantom. CONCLUSION: Its small size and high signal-to-noise ratio, together with immunity to most system nonlinearities and imaging errors, makes the Overhauser marker a promising localization method for the accurate positioning of interventional devices. The method may be applied at any field strength, and markers are visible in images obtained with any practical imaging sequence.

MRI in late sequelae of Perthes' disease: imaging findings and symptomatology in ten hips.

Five painful (group A) and five symptomless (group B) hips in nine patients with late sequelae of Perthes' disease were studied with plain radiography and magnetic resonance imaging (MRI) in order to correlate MRI findings with symptomatology. The unaffected hips were also studied. In group A hips, poor congruence of the articular cartilage surfaces was present in three of five cases, whereas good congruence was found in all group B hips. In one spherical but painful hip (group A), MRI revealed a protuberance in the anterolateral cartilage of the femoral head. The joint cartilage in group A and B hips was, on average, 0.5 and 1.5 mm thicker, respectively, than the cartilage in the unaffected hips. The lateral joint capsule was, on average, 3.0 mm thicker in group A hips than in the unaffected hips (P < 0.05), which possibly reflects reactive changes due to chronic irritation in the painful hips. The mean joint capsule thickness differed by only 0.5 mm between the unaffected and group B hips. Mean anterior acetabular coverage by MRI was 97 % in group A and 98 % in group B, while in the unaffected hips mean anterior coverage was 102 %. In an aspherical painful hip, MRI revealed a juxta-articular cyst not visible by radiography. A symptomless intra-articular fragment, due to osteochondritis dissecans, was well visualized with MRI. MRI is recommended for evaluation of pain in hips with late sequelae of Perthes' disease. It may show abnormalities in bony structures, as well as in joint capsule and cartilage.

Postmarathon paradox: insulin resistance in the face of glycogen depletion.

Acute physical exercise enhances insulin sensitivity in healthy subjects. We examined the effect of a 42-km marathon run on insulin sensitivity and lipid oxidation in 19 male runners. In the morning after the marathon run, basal serum free fatty acid concentration was 2.2-fold higher, muscle glycogen content 37% lower (P < 0.01), glycogen synthase fractional activity 56% greater (P < 0.01), and glucose oxidation reduced by 43% (P < 0.01), whereas lipid oxidation was increased by 55% (P < 0.02) compared with the control study. During euglycemic-hyperinsulinemic clamp, whole body glucose disposal was decreased by 12% (P < 0.01) because of a 36% lower glucose oxidation rate (P < 0.05), whereas the rate of lipid oxidation was 10-fold greater (P < 0.02) than in the control study. After the marathon, muscle glycogen content correlated positively with lipid oxidation (r = 0.60, P < 0.05) and maximal aerobic power (Vo2peak; r = 0.61, P < 0.05). Vo2peak correlated positively with basal lipid oxidation (r = 0.57, P < 0.05). In conclusion, 1) after the marathon run, probably because of increased lipid oxidation, the insulin-stimulated glucose disposal is decreased despite muscle glycogen depletion and the activation of glycogen synthase; 2) the contribution of lipid oxidation in energy expenditure is increased in proportion to physical fitness; 3) these adaptations of fuel homeostasis may contribute to the maintenance of physical performance after prolonged exercise.