F. L. Van de Vyver

Defect in succinate oxidation by isolated muscle mitochondria in a patient with symmetrical lesions in the basal ganglia

A 3-year-old boy was referred for evaluation of psychomotor retardation. He had a waddling gait with proximal hypotonia and paresis. Computed tomography (CT scan) and magnetic resonance imaging (MRI) of the brain demonstrated symmetrical lesions in the basal ganglia suggesting bilateral necrosis. Lactate and pyruvate levels in blood and cerebrospinal fluid were persistently elevated. A biopsy of the quadriceps muscle showed normal light microscopic findings except for a slightly raised number of lipid droplets. Electron microscopy confirmed this and also showed a rather large number of subsarcolemmal mitochondria without crystalline inclusions. Biochemical studies showed a normal carnitine level and normal mitochondrial enzyme activities in muscle homogenate, including succinate-cytochrome c reductase. However, intact isolated mitochondria failed to oxidize succinate. An explanation for this paradoxical finding is a deficiency in that part of the coenzyme Q (CoQ) that is reduced by the succinate dehydrogenase complex. The differential diagnosis between Leighs syndrome and infantile bilateral striatal necrosis (IBSN) is discussed. The role of neuroradiology in prompting complementary investigations is stressed.

HEMOPERFUSION-HEMODIALYSIS INEFFECTIVE FOR PARAQUAT REMOVAL IN LIFE-THREATENING POISONING

We report on a patient treated with hemoperfusion-hemodialysis (HP-HD) for severe paraquat poisoning. This procedure was adopted since the combination of adsorption and dialysis may improve overall drug removal. On admission blood paraquat was 15.8 micrograms/ml. He received conventional treatment and combined HP-HD which started within 3 hours after ingestion of the chemical and lasted 5 hours. Blood samples were obtained during and after HP-HD. The samples during HP-HD were taken before the charcoal column, between the charcoal column and the artificial kidney and after the artificial kidney. Blood clearances of paraquat were 116 +/- 32 ml/min (n=6) for the charcoal column (HP), 90 +/- 54 ml/min (n=6) for the artificial kidney (HD) and 151 +/- 37 ml/min (n=6) for the combined systems (HP-HD). After HP-HD a limited rebound of blood paraquat level was seen. One day after admission renal and hepatic failure had developed, and the patient died after 5 days. Tissue paraquat levels (microgram/g wet tissue) were: skeletal muscle 9.4, pancreas 6.0, prostate 5.6, thyroid 4.2, lungs 4.0, bone marrow 4.0, kidney 3.1, spleen 2.9, adrenal 2.9, heart 2.8, liver 2.3, stomach and testis below 1.0. Measurements of blood levels demonstrated the efficient clearances of paraquat with HP-HD from the central (plasma) compartment. However, the present results confirmed those previously reported which suggest that the efficiency of short HP-HD in treating severe paraquat poisoning is questionable since paraquat levels in the peripheral (tissue) compartment remain elevated.

Improved correlation of magnetic resonance imaging (MRI) with clinical status in multiple sclerosis (MS) by use of an extensive standardized imaging-protocol.

In a previous study we have shown that the sensitivity of magnetic resonance imaging (MRI) for the detection of multiple sclerosis (MS) lesions was improved significantly, especially in the infratentorial region, by use of an extensive standardized MRI-protocol consisting of sagittal T1, axial protondensity and axial T2, and sagittal protondensity and sagittal moderately T2-weighted images. The goal of the present study was to assess whether the clinical correlation of the visualized lesions had improved accordingly. Using a scoring system based on lesion dimensions, we compared 70 MRI examinations performed in 25 patients with definite MS, with the relevant clinical data as given by the Expanded Disability Status Scale (EDSS) and Functional System scale (FS). We found a significant correlation (r = 0.66, P = 0.0001) between the MRI score and the EDSS. Significant correlations also existed between MRI scores and cerebellar and brainstem FS scores. These correlations were consistently higher than those reported by other authors. We conclude that a standardized MRI examination, including sagittal protondensity and moderately T2-weighted images, should be performed in every MS patient. The improved clinical correlation could be of importance in follow-up studies when assessing the efficacity of therapy.

Acromegaly, multinodular goiter and silent polyostotic fibrous dysplasia. A variant of the McCune-Albright syndrome

A 36-year-old woman is reported with a possible variant of the McCune-Albright syndrome. The triad was incomplete because of the absence of skin pigmentation and since the sexual precocity was not evident. The presence of a pituitary mass and the secretory dynamics of growth hormone and prolactin were suggestive of a mam-mosomatotroph cell adenoma. A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. Unusual was the silent evolution of the polyostotic fibrous dysplasia, which was only fortuitously discovered during magnetic resonance imaging of the pituitary region. Treatment of the acromegaly with the long-acting somatostatin analogue octreotide resulted in an important inhibition of the GH secretion and in a reduction of the volume of the pituitary adenoma.

Photochemically-induced cerebral infarction in the rat: Comparison of NMR imaging and histologic changes

SummaryThe evolution of a photochemically induced cerebral thrombotic infarction was followed in rats during the first week after the insult by means of NMR imaging and histology. Heavily T2-weighted images provided an excellent lesion detection and a high specificity for the discrimination of different histological abnormalities. The T2-weighted images showed a brain lesion evolving during the first 24h from a homogeneous hyperintense area, histologically corresponding to diffuse vasogenic and cytotoxic oedema with concomitant neuronal necrosis, to an iso-intense area with a hyperintense seam, which microscopically correlated with increased vascular permeability at the periphery of the lesion. The hyperintense seam was observed up to day 7, but at that time coincided with gliomesodermal repair reaction which could be verified histochemically and ultrastructurally. It may be concluded that NMR-micro-imaging at a moderately high field, enables early detection and adequate followup of small cerebral infarctions in rats.

Long term follow-up of multiple sclerosis by standardized, non-contrast-enhanced magnetic resonance imaging

The usefulness of non-contrast-enhanced, standardized magnetic resonance imaging for the longterm follow-up of MS patients was evaluated in a retrospective study in 36 patients with clinically definite MS. All had remitting-relapsing diseases courses. Sixteen patients remained clinically stable during follow-up. Mean duration of follow-up was 22 months (SD: 11). A mean number of 3 MRI examinations was performed in each of the patients (SD: 1). Subclinical evolution was detected in 56% of the stable patients, indicating that clinical data alone are insufficient to assess disease activity. The relapsing patients showed significantly more and larger changes on MRI than stable patients (P less than 0.001), indicating that MRI is well suited as a follow-up parameter in conjunction with clinical data. The time courses of these quantitative changes and of the qualitative changes of putative MS lesions on MRI are discussed. It is concluded that MRI is a good indicator of global disease activity in multiple sclerosis patients, which makes MRI very useful for the evaluation of therapeutic trials.

High resolution nuclear magnetic resonance imaging of the spinal cord in experimental demyelinating disease

SummaryChronic recurrent experimental allergic encephalomyelitis was induced in a strain 13 guinea pig by inoculation of isologous spinal cord homogenate. The spinal cord was obtained after perfusion with 4% paraformaldehyde and examined with nuclear magnetic resonance (NMR) imaging. Proton NMR spin echo images (repetition time: 3 s; echo times: 20 and 60 ms) were obtained from intact, isolated spinal cord in a 4.7 Tesla, 50 mm bore magnet. The slice thickness of the images was 380 μm and the inplane resolution was 40×40 μm. The images showed superficial areas of low signal intensity in the lateroventral regions of the white matter, in some instances with a seam of higher signal intensity. Neuropathologically, these abnormalities corresponded exactly to areas of demyelination. Control images did not show these abnormalities. The present high resolution imaging allowed a correlation between demyelination and abnormal NMR signals in a small laboratory animal with an inflammatory demyelinating disease.

Noninvasive in vivo 13C-NMR spectroscopy of a 13C-labeled xenobiotic in the rat

This study demonstrates that the xenobiotic product, 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloro-3-13C-propane can be monitored in the liver of an intact animal by in vivo 13C surface coil NMR spectroscopy after intraperitoneal administration. The carbon-13 label could be detected after a single dose of only 200 mg/kg of the product. The intrahepatic changes of the signal intensity of the labeled product were monitored as a function of time. No signals corresponding to metabolites could be detected.

Use of Laser Microprobe Mass Analysis (LAMMA) for Localizing Multiple Elements in Soft and Hard Tissues

The potential of laser microprobe mass analysis (LAMMA) as a sensitive microanalytical technique was explored in applications relevant to nephrology. Aluminum and associated elements, such as iron, were localized in fresh tissue biopsies obtained from uremic patients treatment by chronic hemodialysis. The LAMMA was applied to serum, liver, bone, and parathyroid glands of such patients. In addition, we used LAMMA to evaluate the specificity and sensitivity of routine histochemistry, in particular on human bone sections stained by the aluminon method. The high, multielemental sensitivity and molecular microprobe potential of LAMMA established important advantages over other microchemical methods forin situ analysis at the micron level in histological sections.

High resolution NMR imaging: Gd-DTPA labeled enzyme as a probe for permeability studies in polyacrylamide gels

The penetration of horse liver alcohol dehydrogenase (HLAD) molecules into polyacrylamide gel beads, which are used to immobilize the enzyme, was studied. HLAD was labeled with gadolinium diethylene-triamine-pentaacetic acid (Gd-DTPA), using the N-hydroxy-succinimide active ester of DTPA as a chelating agent. The HLAD-(Gd-DTPA)27 has a 3.7-fold larger longitudinal (R1) and a 14-fold larger transversal relaxivity (R2) (at 2.4 T) than the plain Gd-DTPA. A series of dry polyacrylamide gel beads, with total monomer concentration ranging from 5% to 30% were synthesized and swollen in a buffered solution of HLAD-(Gd-DTPA)27. The gel beads were examined with high resolution NMR imaging. The T1- and T2-weighted images revealed that the permeability for the labeled HLAD decreased with increasing total monomer concentration of the gel beads. These imaging results correlate fairly well with the enzymatic reactivities measured for the same range of gel beads but swollen in a solution of non labeled HLAD and NAD+ (nicotinamide adenine dinucleotide). It is concluded that Gd-labeling can be used to monitor the distribution of weakly concentrated, water soluble products in a solid matrix.