Proton MR Spectroscopy in Brain Metabolic Disorders

Metabolic disorders of the central nervous system (CNS) include pathologies with extremely different pathogenesis. The clinical diagnosis of these disorders is often very difficult and requires sophisticated laboratory investigations. Proton magnetic resonance (MR) spectroscopy (1H-MRS) has recently been used in a number of clinical studies to supplement conventional MRI as it is able to provide in vivo biochemical assay of a given brain tissue. Brain data on several neurometabolic diseases suggest that 1H-MRS can provide in vivo chemical-pathologic characterization of the abnormality visualized by magnetic resonance imaging (MRI) and can detect metabolic alterations in tissue appearing normal on conventional MRI. This may help for differential diagnosis and can be important in the evaluation of disease outcome. Indices provided by 1H-MRS have been demonstrated to be relevant to patients' clinical status, to represent sensitive indicators of early neurologic involvement and to be helpful in monitoring effects of therapeutic interventions. This suggests that, in the next future, a more extensive use of brain 1H-MRS in the management of patients with metabolic disorders affecting CNS should be encouraged

Proton magnetic resonance spectroscopy of the brain in dementia

Proton magnetic resonance spectroscopy (MRS) allows accurate and noninvasive biochemical assay of living tissues. In vivo measurements provided by MRS have greatly enhanced our understanding of the pathophysiology of dementia. Increases in choline and myo-inositol (markers of membrane turnover) have been demonstrated in several studies on patients with Alzheimer's disease (AD), suggesting the presence of a significant cellular membrane (and glial) pathology in this disorder. Large decreases in brain N-acetylaspartate (NAA) (a marker of neuroaxonal integrity) are commonly seen in AD as well as in other forms of dementia in cerebral gray and white matter, indicating the presence of significant axonal damage. Since greater NAA decreases have been demonstrated in brains of patients with clinically more severe disease, NAA could provide an index relevant to patients' clinical status. Brain metabolic changes can be independent of abnormalities detected by conventional magnetic resonance imaging (MRI), since proton MRS may show a normal metabolic pattern in patients with mild neurological impairment and severe MRI abnormalities. However, quantitative measurements of regional brain volumes can be useful in the diagnosis of dementia. Thus, proton MRS, alone or combined with new quantitative magnetic resonance techniques, can provide sensitive indices able to monitor disease progression or effects of drug therapy

Magnetic resonance imaging and spectroscopy changes in brains of patients with cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to an inherited defect in the metabolic pathway of cholesterol. Early diagnosis of the disease is particularly important as patients benefit from therapy with chenodeoxycholic acid. Although the disease is clinically characterized by the concomitant presence of tendon xanthomas, juvenile cataracts and progressive neurological impairment, clinical features may vary greatly. Neuroradiological studies have suggested that the bilateral abnormality of the dentate nuclei could be typical of this disease. However, this finding has been seen inconsistently on conventional MRI. The dynamic of the CNS pathology in CTX is complex, and whether demyelination or axonopathy has primary importance in the pathogenesis of CTX pathology is not known. To clarify both neuroradiological and pathological issues, we performed combined brain MRI and spectroscopy examinations on 12 CTX patients. On conventional MRIs, bilateral hyperintensities of the dentate nuclei were clearly seen in nine out of 12 patients on T(2) -weighted MRIs, but were evident in all patients using a FLAIR sequence. On proton magnetic resonance (MR) spectroscopy, significant decreases in N: -acetylaspartate resonance intensities (P: <0.0001) and increases in lactate MR signals (P<0.05) were found in the group of CTX patients in large volumes of interest localized above the lateral brain ventricles and in the cerebellar hemispheres. Cerebral values of N -acetylaspartate resonance intensities showed a close correlation with patients' disability (Spearman rank correlation = -0.78, P<0.005). These results suggest that MR abnormalities in the dentate nuclei may be evident consistently in patients with CTX. Proton MR spectroscopy data demonstrated widespread axonal damage (as shown by the decrease in N -acetylaspartate) and diffuse brain mitochondrial dysfunction (as shown by the increase in brain parenchymal lactate) in patients with CTX. The close correlation seen between values of the putative axonal marker N-acetylaspartate and patients' disability scores suggests that proton MR spectroscopy can provide a useful measure of disease outcome in CTX

The treatment of iatrogenic injuries of CBD: Surgery vs endoprostheses

Analysis of the long-term results of 83 Roux-en-Y bilio-enteric anastomosis and 25 endoscopic stentings for iatrogenic biliary strictures, has allowed, in spite of drawbacks of a retrospective study, the identification of good indications for treatment. The good long-term results of surgical treatment (84.3%) after a mean follow-up of 8.5 years, have a favorable relationship with an intrahepatic preexisting dilatation of the biliary tree in the absence of chronic rough inflammation of the biliary wall. Otherwise, endoscopic stenting can be a good indication both as definitive treatment and complementary to surgery. On the contrary, the Hutson-Russell loop cutaneous choledochojejunostomy can represent a viable access to intrahepatic biliary tree for endoscopic instrumentation in case of recurrent anastomotic stricture. The long-term results are roughly similar after endoscopic (mean follow-up 23.6 months) and surgical treatment. The cases with unsatisfactory evolution after endoscopic management are the long strictures with late treatment with long-standing biliary infections. Nevertheless follow-ups of endoscopic series are too short to say that long-term results are really definitive. Short and incomplete strictures with bilio-cutaneous fistula have to be thought a good indication to endoscopic treatment. In our opinion self-expanding metallic stents have not to be used in benign strictures

Severe Metabolic Abnormalities in the White Matter of Patients with Vacuolating Leukoencephalopathy with Subcortical Cysts. A Proton MR Spectroscopic Imaging Study

Vacuolating megalencephalic leukoencephalopathy (VML) with subcortical cysts is a neurodegenerative disorder clinically characterized by megalencephaly with onset in the first year of life, progressive ataxia, spasticity and relatively spared cognitive function. Conventional MRI findings consist of diffusely abnormal cerebral white matter with subcortical cysts. Recent single-voxel proton MR spectroscopy studies have shown mild metabolic abnormalities in the white matter. We report here a combined proton MR imaging and MR spectroscopic imaging (1H-MRSI) study on 2 new, unrelated patients with this rare disorder. 1H-MRSI examinations, which can provide simultaneously metabolic information from many different brain regions, showed inhomogeneous decreases in all normally detected metabolites with significant widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine and concomitant small increases in lactate in the white matter of both hemispheres. Metabolic abnormalities were milder in the frontal white matter and more severe in the posterior white matter. The 1H-MRSI pattern of the gray matter was normal in both patients. In one patient, a subsequent 1H-MRSI examination (performed 3 years after the first) confirmed the presence of widespread decreases in the ratio of N-acetylaspartate to creatine+phosphocreatine in the white matter. We conclude that severe metabolic abnormalities can be found in the white matter of VML patients. This suggests that, despite the apparently mild clinical course, a severe neurodegenerative process may occur in the white matter of these patients