L-2 hydroxyglutaric aciduria: proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging findings

A 10-month-old boy was reported with the diagnosis of L-2 hydroxyglutaric aciduria. Amino acid chromatographic analysis revealed an 80-fold increase of hydroxyglutaric acid in the urine. Proton magnetic resonance (MR) spectroscopy of the brain obtained with the hybrid chemical shift imaging sequence (repetition time = 1,500 milliseconds, echo time = 40 milliseconds) revealed prominent peaks resonating at 2.50 ppm, which were attributable to L-2 hydroxyglutaric acid. Diffusion MR imaging was obtained using the echo-planar trace sequence (repetition time = 5,700 milliseconds, echo time = 139 milliseconds). Two different diffusion patterns were evident: a restricted diffusion pattern in the globi pallidi and an increased diffusion pattern in the white matter.     

MRI in 3-methylglutaconic aciduria type 1

MRI in a young child with 3-methylglutaconic aciduria type 1 showed signal abnormalities in the basal ganglia which progressed despite successful treatment. Received: 4 March 1999 Accepted: 25 March 1999     

Effect of sodium and acetate ions on 8-hydroxyguanine formation in irradiated aqueous solutions of DNA and 2′-deoxyguanosine 5′-monophosphate

Abstract

Purpose: The aim of this work was to study the combined effect of sodium and acetate ions on the radiation yield of 8-hydroxyguanine (8-OHG), one of the major DNA base lesions induced by free radicals.

Materials and methods: Aqueous solutions of DNA and 2′-deoxyguanosine 5′-monophosphate (dGMP) with various concentrations of sodium acetate and sodium perchlorate were γ-irradiated, enzymatically digested and analyzed by high-performance liquid chromatography (HPLC) methods.

Results: It was found that both salts decrease the 8-OHG radiation yield in the concentration range studied for both DNA and dGMP, except in the case of dGMP wherein an increase in yield occurs in the concentration range from 0.1–1 mM. The dependence of the 8-hydroxy-2′-deoxyguanosine radiation yield on the concentration of both sodium acetate and sodium perchlorate have different shapes and have steeper slopes for the DNA compared with the dGMP solutions.

Conclusions: The observed decrease in the radiation yield of 8-OHG with increasing concentrations of sodium acetate is consistent with the hypothesis that sodium acetate produces two concentration-dependent effects in the DNA solutions: (1) A conformational change in the DNA caused by Na⁺ counterions; and (2) free radical reactions related to the radiolysis of acetate ion.     

Diffusion-weighted MR imaging in leukodystrophies

Leukodystrophies are genetically determined metabolic diseases, in which the underlying biochemical abnormality interferes with the normal build-up and/or maintenance of myelin, which leads to hypo- (or arrested) myelination, or dysmyelination with resultant demyelination. Although conventional magnetic resonance imaging has significantly contributed to recent progress in the diagnostic work-up of these diseases, diffusion-weighted imaging has the potential to further improve our understanding of underlying pathological processes and their dynamics through the assessment of normal and abnormal diffusion properties of cerebral white matter. Evaluation of conventional diffusion-weighted and ADC map images allows the detection of major diffusion abnormalities and the identification of various edema types, of which the so-called myelin edema is particularly relevant to leukodystrophies. Depending on the nature of histopathological changes, stage and progression gradient of diseases, various diffusion-weighted imaging patterns may be seen in leukodystrophies. Absent or low-grade myelin edema is found in mucopolysaccharidoses, GM gangliosidoses, Zellweger disease, adrenomyeloneuropathy, L-2-hydroxyglutaric aciduria, non-ketotic hyperglycinemia, classical phenylketonuria, Van der Knaap disease and the vanishing white matter, medium grade myelin edema in metachromatic leukodystrophy, X-linked adrenoleukodystrophy and HMG coenzyme lyase deficiency and high grade edema in Krabbe disease, Canavan disease, hyperhomocystinemias, maple syrup urine disease and leukodystrophy with brainstem and spinal cord involvement and high lactate.     

Stoffwechselstörungen mit typischen Veränderungen im MRT

The classification of metabolic disorders according to the etiology is not practical for neuroradiological purposes because the underlying defect does not uniformly transform into morphological characteristics. Therefore typical MR and clinical features of some easily identifiable metabolic disorders are presented. Canavan disease, Pelizaeus-Merzbacher disease, Alexander disease, X-chromosomal adrenoleukodystrophy and adrenomyeloneuropathy, mitochondrial disorders, such as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and Leigh syndrome as well as L-2-hydroxyglutaric aciduria are presented.     

甲基丙二酸尿症及丙酸尿症的颅脑MRI研究

目的:探讨甲基丙二酸尿症及丙酸尿症的颅脑MRI表现。方法:对16例甲基丙二酸尿症和丙酸尿症的婴幼患儿的临床资料及颅脑MRI进行分析总结。结果:16例中男10例,女6例,发病年龄为出生后～2岁。治疗前行头颅MRI检查8例,表现为脑萎缩5例,其中3例伴脑白质减少,另2例伴双侧基底节信号异常,表现为T1FLAIR稍低、T2FLAIR高信号、DWI高信号;头颅CT检查1例,表现为交通性脑积水。通过治疗后随访MRI7例,表现为MRI和DWI阴性1例,双侧基底节持续T1FLAIR稍低、T2FLAIR高信号、DWI稍高信号1例,内囊前后肢及脑干T1FLAIR低信号1例;余4例中,MRI表现好转2例,呈进行性改变2例。结论:甲基丙二酸尿症和丙酸尿症的MRI表现缺乏特异性,主要为不同程度的脑萎缩、髓鞘化延迟和基底节的异常信号,特别是苍白球。MRI的异常改变可通过合理治疗而有所改善,然而长期的异常影像学改变则预示着神经系统呈不可逆的、进行性的损害。     

Imaging findings in patients with myelofibrosis

The purpose of this review is to illustrate the wide range of radiological abnormalities in myelofibrosis. Myelofibrosis, also called myeloid metaplasia, is a myeloproliferative disorder of unknown etiology. The common imaging findings in patients with myelofibrosis are osteosclerosis, hepatosplenomegaly, and lymphadenopathies. In addition, extramedullary hematopoiesis may develop in multiple sites such as chest, abdomen, pelvis, and central nervous system, simulating malignant disease. Selected plain-film, CT, and MR images in patients with myelofibrosis are shown as pictorial essay to allow ready recognition of the most common imaging abnormalities of the disease. Received: 6 August 1998; Revision received: 15 October 1998; Accepted: 20 November 1998     

MR contribution in surgery of epilepsy

The contribution of MR imaging in patients with drug-resistant epilepsy considered for surgical therapy is discussed. In this review we focus on: (a) focal abnormalities (mesial temporal sclerosis, focal migration disorders, hamartomatous lesions and low-grade tumours, phakomatosis and vascular malformations) associated with therapy-resistant partial epilepsy, requiring resective surgery; (b) abnormalities leading to generalized seizures that require more drastic surgical procedures, such as callosotomy and functional hemispherectomy; and (c) localisation of implanted depth-electrodes. Received: 6 April 1998; Revision received: 2 June 1998; Accepted: 3 June 1998     

Carotid canal dehiscence in the human skull

Abnormalities of the floor of the carotid canal have been studied in 538 skulls. These abnormalities range from a fissure to total absence of the floor. This variation may be caused by abnormalities of the internal carotid artery or deficiencies in ossification of the skull base. CT suggests that these changes should be taken into account by surgeons working on the skull base. Received: 19 June 1998 Accepted: 14 October 1998     

Rostral vermian cortical dysplasia: MRI

The MRI findings in rostral vermian dysplasia are described for the first time. Defective foliation and abnormal fissuration of the rostral vermis can clearly be depicted on coronal images. The abnormalities are limited to the anterior lobe of the vermis and its hemisphere extension. A hypothesis is put forward to explain the abnormalities. It is suggested that the vermian changes result from an intrauterine insult at the end of the first trimester. There appears to be a variable degree of expression and associated cerebellar and cerebral cortical abnormalities can be seen. The clinical significance of these findings remains incompletely understood but may be related to the severity of the abnormalities. It is also suggested that a mild degree of vermian rostral dysplasia may represent an incidental imaging finding. Received: 10 May 1998 Accepted: 23 June 1998     

Metaphyseal chondromatosis combined with D-2-hydroxyglutaric aciduria in four patients

We report four patients who presented with a severe form of metaphyseal chondromatosis in association with D-2-hydroxyglutaric aciduria (D-2-HGA). All patients showed splaying columns of irregular ossification defects with bulbous metaphyses of the long tubular bones, as well as remarkable involvement of the short tubular and flat bones. The vertebral bodies revealed platyspondyly with irregular, stippled endplates. D-2-HGA has been described as a neurometabolic disorder manifesting a broad range of impairment in mental and motor development. Although hydroxyglutaric acid was excreted in high amounts in the urine of all four patients described herein, no significant neurologic abnormalities were evident. This unusual combination of characteristic skeletal and metabolic abnormalities has rarely been reported. Thus, our report will facilitate the recognition of this distinctive entity, and we suggest that a urine organic acid screening be obtained in patients who present with generalized enchondromatosis.     

Proteus syndrome: craniofacial and cerebral MRI

The Proteus syndrome is a rare hamartoneoplastic syndrome that may affect the brain, skull, and extracranial head and neck. We present a case with severe, characteristic findings. Brain abnormalities are not common in Proteus syndrome; when present, hemimegalencephaly and migrational disorders are typically seen, commonly with an associated seizure disorder. Maxillary and mandibular dysmorphism may occur, including unilateral condylar hyperplasia. Subcutaneous fatty, fibrous, lymphangiomatous masses commonly seen in this syndrome may involve the neck and face, leading to disfigurement and potential airway compromise. Received: 9 September 1998 Accepted: 28 December 1998     

White-matter abnormalities in unirradiated patients cured of primary central nervous system lymphoma

On MRI, primary brain tumors are commonly seen as contrast-enhancing masses surrounded by areas of abnormal signal on T2-weighted images. Following successful treatment tumors may no longer show contrast enhancement. The residual abnormalities are assumed to be represent “edema” and infiltrating tumor cells. We report nine patients with primary lymphoma of the central nervous system who had complete responses to intravenous methotrexate, but did not receive intrathecal chemotherapy or cranial irradiation. After complete resolution of contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the region of prior tumor were initially assumed to reflect residual viable tumor. As they remained unchanged for years, however, this may not hold true in the cases in which primary central nervous system lymphoma responds to chemotherapy alone. Received: 14 August 1998 Accepted: 11 August 1999     

Diffusion magnetic resonance imaging patterns in metabolic and toxic brain disorders

Purpose: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI).

Material and Methods: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5T with a gradient strength of 30 mT/meter, and a rise time of 600 μs. b=1000 s/mm² images and apparent diffusion coefficient (ADC) maps with ADC values were studied.

Results: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b=1000 s/mm² images and low ADC values); 2. an elevated diffusion pattern (normal signal on b=1000 s/mm² images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n=2), phenylketonuria (n=3), maple syrup urine disease (intermediate form) (n=1), infantile neuroaxonal dystrophy (n=1), Leigh (n=2), Wilson (n=3), and Canavan disease (n=1). Disorders with an elevated diffusion pattern included phenylketonuria (n=1), adrenoleukodystrophy (n=1), merosin-deficient congenital muscular dystrophy (n=2), mucopolysaccharidosis (n=2), Lowe syndrome (n=1), Leigh (n=2), Alexander (n=1), Pelizaeus-Merzbacher (n=1), and Wilson (n=3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n=2), non-ketotic hyperglycinemia (n=1), infantile neuroaxonal dystrophy (n=2), maple syrup urine disease (n=1), and Leigh (n=1) disease.

Conclusion: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated diffusion pattern to disintegration of the tissue. The mixed pattern has contributions from both myelin abnormalities related to myelin disintegration of the tissue.     

Frequency and spectrum of abnormalities in the bone marrow of the wrist: MR imaging findings

Objective. To describe the frequency of marrow abnormalities on wrist MR imaging and the MR findings of these various abnormalities. Design and patients. Five hundred and nineteen patients were studied at 1.5 T. Two observers recorded the presence and location of avascular necrosis, occult fractures and arthritic edema [focal osteoarthritis, ulnolunate abutment, rheumatoid arthritis, septic arthritis, gouty arthritis and scapholunate advanced collapse (SLAC)]. Results and conclusion. One hundred and eighty-seven (36%) patients demonstrated marrow abnormalities in the wrist, of which 101 were diagnosed as arthritis [64 (34%) as focal osteoarthritis, 17 (9%) as ulnolunate abutment, 15 (8%) as rheumatoid arthritis, 2 as septic arthritis, 2 as SLAC, and 1 as gouty arthritis]. Seventy-two patients had occult fractures and in 27 patients avascular necrosis was seen. MR imaging can reveal various abnormalities in bone marrow of the wrist when findings on radiography are normal or equivocal. Received: 29 May 1998 Revision requested: 8 July 1998 Revision received: 8 December 1998 Accepted: 22 January 1999     

Screening applications for MRI in the detection of upper abdominal disease: comparative study of non-contrast-enhanced single-shot MRI and contrast-enhanced helical CT

Purpose: To compare the value of ’push-button' singe-shot non-contrast-enhanced MRI and contrast-enhanced helical CT for detection of upper abdominal disease. Methods: In 120 patients, images obtained with non contrast-enhanced single-shot MRI (T2: double echo HASTE, and T1: turbo FLASH) and contrast-enhanced helical CT were compared. Lesions or abnormalities were divided in 8 anatomical categories (1: liver; 2: pancreatobiliary; 3: kidney/adrenal gland; 4: retroperitoneum; 5: vascular; 6: spleen; 7: gastrointestinal tract and peritoneum; 8: base of thorax) and classified as follows: 2: seen at MRI only; 1: better seen at MRI; 0: no difference; −1: better seen at CT; −2: seen at CT only. Also recorded were the 'door-to-door’ examination times. Results: Of a total of 629 abnormalities, 594 were detected at MRI (94 %) and 536 at CT (85 %). CT offered better results in two categories only: retroperitoneum (mean score: −0.68) and vascular (mean score −0.87). Mean examination times were 19 min for CT and 14.8 min for MRI. Conclusion: Unenhanced single-shot MRI is a valuable first step of a comprehensive upper abdominal MR exam and may even be the final step in many patients. Received: 3 April 1998; Revision received: 13 July 1998; Accepted: 18 August 1998     

Early-onset combined methylmalonic aciduria and homocystinuria: neuroradiologic findings

BACKGROUND AND PURPOSE: Combined methylmalonic aciduria and homocystinuria (MMA-HC) is caused by impaired hepatic conversion of dietary cobalamin to methylcobalamin and adenosylcobalamin, resulting in decreased activity of methylmalonyl-CoA mutase and methionine synthase. Patients with the early-onset variety present within 12 months of age with severe neurologic, hematologic, and gastrointestinal abnormalities. We describe the neuroradiologic features of early-onset MMA-HC and discuss related pathophysiological mechanisms. METHODS: Twelve infants with hypotonia, failure to thrive, poor feeding, and hematologic abnormalities were diagnosed with MMA-HC on the basis of a typical plasmatic and urinary metabolic profile and enzyme activity in fibroblastic cultures. Complementation studies were performed in two cases, and yielded a CblC result. MR imaging was performed at presentation in four cases and later in the others. All patients showed prompt biochemical improvement with intramuscular hydroxocobalamin administration, and most had moderate neurologic improvement. RESULTS: Diffuse supratentorial white matter edema and dysmyelination was the typical MR picture at presentation, whereas white matter bulk loss characterized later stages of the disease. Nucleocapsular areas of gliosis were an additional finding in one case. One patient had tetraventricular hydrocephalus at presentation. CONCLUSION: White matter damage is probably caused by reduced methyl group availability and nonphysiological fatty acids toxicity, whereas focal gliosis results from homocysteine-induced toxicity to the endothelium. Hydrocephalus may result from diffuse intracranial extracerebral arterial stiffness, known as reduced arterial pulsation hydrocephalus. MR imaging features at presentation and at follow-up are nonspecific.     

Bronchiolar inflammatory diseases: high-resolution CT findings with histologic correlation

Bronchiolar diseases pose a significant challenge to the clinician confronted with the evaluation and management of the affected patient. A variety of infectious and non-infectious diseases may affect the bronchioles causing either reversible or fixed bronchiolar obstruction. High-resolution CT (HRCT) is currently the best imaging modality for evaluation of small-airway disease. In fact, a wide spectrum of abnormalities are identified at HRCT in patients with bronchiolar diseases. These abnormalities are shown on HRCT in the presence of a normal or unclear chest radiograph. Additionally, HRCT performed at suspended full expiration may demonstrate the physiologic consequences of bronchiolar disease, e. g., air trapping. The differential diagnosis of pulmonary manifestations of bronchiolar diseases at HRCT is based on the different patterns of abnormality. Familiarity with the presentation of different bronchiolar inflammatory processes aid the radiologist in narrowing the differential diagnosis or even in suggesting a specific diagnosis. This article reviews the HRCT findings of various bronchiolar inflammatory diseases outlining their pathologic features. Knowledge of the underlying gross and microscopic pathologic features leads to a better understanding of their CT appearances. Received: 23 January 1998; Revision received: 14 August 1998; Accepted: 10 February 1999     

Dynamic contrast-enhanced subtraction MR angiography in intracranial vascular abnormalities

We present our clinical experience with dynamic contrast-enhanced MR angiography (MRA) with subtraction for assessing intracranial vascular abnormalities. Ten patients with various cerebrovascular disorders underwent dynamic contrast-enhanced MRA on a 1.0-T system. Thirty sections (2 mm) were acquired in 29–30 s. Maximum intensity projection images and subtracted source images were compared with those obtained by conventional angiography. In all cases, the presence or absence of abnormalities in the targeted vessels, as well as the morphology of the sagittal sinuses, was clearly visualized as in conventional angiography, without any obstructions such as hyperintense hematomas or thrombi, or intraluminal turbulence. Although the temporal and spatial resolutions with current hardware are insufficient, these preliminary results suggest that dynamic contrast-enhanced MRA with subtraction may be useful for assessing vascular lesions with hemorrhage or thrombus, and the dural sinuses. Received: 4 November 1998; Accepted: 17 May 1999     

Congenital muscular dystrophy with merosin deficiency: MRI findings in five patients

We present the MRI findings in five patients with congenital muscular dystrophy (CMD) and merosin (laminin α 2) deficiency, which was total in one and partial in four. In one patient with partial merosin deficiency, MRI was normal. The other four patients had supratentorial white matter abnormalities. In three, T2-weighted images revealed subcortical, deep lobar and periventricular high signal in white matter, while in the other there were only small peritrigonal areas of increased signal. On T1-weighted images, there was slightly low signal. Cortical abnormalities were absent. None of these changes were accompanied by symptoms or signs of central nervous system involvement. White matter abnormalities in a patient with CMD should prompt investigation of merosin. Received: 22 December 1997 Accepted: 22 April 1998