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Brain white matter tracts degeneration in Friedreich ataxia. An in vivo MRI study using tract-based spatial statistics and voxel-based morphometry

BACKGROUND AND PURPOSE Neuropathological examination in Friedreich ataxia (FRDA) reveals neuronal loss in the gray matter (GM) nuclei and degeneration of the white matter (WM) tracts in the spinal cord, brainstem and cerebellum, while the cerebral hemispheres are substantially spared. Tract-based spatial statistics (TBSS) enables an unbiased whole-brain quantitative analysis of the fractional anisotropy (FA) and mean diffusivity (MD) of the brain WM tracts in vivo. PATIENTS AND METHODS We assessed with TBSS 14 patients with genetically confirmed FRDA and 14 age- and sex-matched healthy controls who were also examined with voxel-based morphometry (VBM) to assess regional atrophy of the GM and WM. RESULTS TBSS revealed decreased FA in the inferior and superior cerebellar peduncles and the corticospinal tracts in the medullary pyramis, in WM tracts of the right cerebellar hemisphere and in the right occipito-frontal and inferior longitudinal fasciculi. Increased MD was observed in the superior cerebellar peduncles, deep cerebellar WM, posterior limbs of the internal capsule and retrolenticular area, bilaterally, and in the WM underlying the left central sulcus. Decreased FA in the left superior cerebellar peduncle correlated with clinical severity. VBM showed small symmetric areas of loss of bulk of the peridentate WM which also correlated with clinical severity. CONCLUSIONS TBSS enables in vivo demonstration of degeneration of the brainstem and cerebellar WM tracts which neuropathological examination indicates to be specifically affected in FRDA. TBSS complements VBM and might be a more sensitive tool to detect WM structural changes in degenerative diseases of the CNS.

Brain white matter damage in SCA1 and SCA2. An in vivo study using voxel-based morphometry, histogram analysis of mean diffusivity and tract-based spatial statistics

BACKGROUND AND PURPOSE Neurodegeneration in spinocerebellar ataxia type 1(SCA1) and 2(SCA2) is associated with white matter(WM) damage. Voxel-Based Morphometry(VBM), histogram analysis of mean diffusivity(MD) and Tract-Based Spatial Statistics(TBSS) enable an in vivo quantitative analysis of WM volume and structure. We assessed with these 3 techniques the whole brain WM damage in SCA1 and SCA2. PATIENTS AND METHODS Ten patients with SCA1, 10 patients with SCA2 and 10 controls underwent MRI with acquisition of T1-weighted and diffusion tensor images. The results were correlated with severity of clinical deficit. RESULTS VBM showed atrophy of the brainstem and cerebellar WM without significant differences between SCA1 and SCA2. Focal atrophy of the cerebral subcortical WM was also present. Histogram analysis revealed increased MD in the brainstem and cerebellum in patients with SCA1 and SCA2 which in SCA2 was more pronounced and combined with mild increase of the MD in the cerebral hemispheres in SCA2. In SCA1 and SCA2 TBSS revealed decreased fractional anisotropy(FA) in the inferior, middle and superior cerebellar peduncles, pontine transverse fibres, medial and lateral lemnisci, spinothalamic tracts, corticospinal tracts and corpus callosum. The extent of tract changes was greater in SCA2 patients who also showed decreased FA in the short intracerebellar tracts. In both diseases VBM, histogram and TBSS results correlated with clinical severity. CONCLUSIONS Brain WM damage featuring a pontocerebeellar atrophy is similar in SCA1 and SCA2 but more pronounced in SCA2. In both diseases it correlates with severity of the clinical deficit.

Risk-benefit analysis of X-ray exposure associated with lung cancer screening in the Italung-CT trial.

OBJECTIVE Prior analyses of X-ray exposures in lung cancer screening with CT considered the basic acquisition technique in single-detector scanners and the effects of a lifetime screening regimen, whereas the potential benefit in terms of lives saved was not addressed. MATERIALS AND METHODS We determined the total-body effective dose of different acquisition techniques for one single-detector and one MDCT scanner and made projections about the cumulative radiation exposure to smokers undergoing four annual CT examinations on the same scanners in the Italung-CT Trial. Combining these data with estimates of radiation-induced fatal cancer and of the benefit of screening, we calculated the risk-benefit ratio for participants in the trial, ex-smokers, and never-smokers. RESULTS The cumulative effective doses per 1,000 subjects were 3.3 Sv using an MDCT scanner and 5.8 or 7.1 Sv using a single-detector scanner. Potential fatal cancers associated with radiation exposure were 0.11 per 1,000 subjects for MDCT scanners and 0.20 or 0.24 for single-detector scanners, which is about 10-100 times lower than the number of expected lives saved by screening assuming a 20-30% lung cancer-specific mortality reduction in current smokers. They were, however, of similar magnitude to the lives saved by screening in never-smokers and former smokers assuming a 10% efficacy of screening. CONCLUSION MDCT is associated with lower radiation doses than single-detector CT technology. The risk of radiation dose in the Italung-CT Trial is compensated for by the expected benefit. CT screening for lung cancer should not be offered to never-smokers, whereas its recommendation in former smokers is debatable.

ADC mapping of neurodegeneration in the brainstem and cerebellum of patients with progressive ataxias.

Analysis of the apparent diffusion coefficient (ADC) maps derived from diffusion-weighted MR imaging is emerging as a reproducible, sensitive, and quantitative tool to evaluate brain damage in diseases of the white and gray matter. To explore the potentials of ADC maps analysis in degenerative ataxias, we examined 28 patients and 26 age-matched controls with T1, T2, and diffusion (b values 0-1000 along the three main body axes)-weighted MR images. Twenty-four patients had inherited genetically proven diseases including spinocerebellar ataxia type 1 (SCA1) (n = 9), spinocerebellar ataxia type 2 (SCA2) (n = 8), and Friedreichs ataxia (FA) (n = 7), whereas four patients had sporadic adult onset pure cerebellar ataxia (three idiopathic, one gluten intolerance). Area and linear measurements of the CNS structures contained in the posterior cranial fossa (PCF) preliminary enabled classification of the patients in the three morphological categories reflecting the gross pathology findings, namely olivopontocerebellar atrophy (OPCA) (n = 10: six SCA2 and four SCA1), spinal atrophy (SA) (n = 7: all FA), and cortical cerebellar atrophy (CCA) (n = 4: three idiopathic and one gluten intolerance). Seven patients with SCA1 (n = 5) or SCA2 (n = 2) had morphologic changes reminiscent of OPCA, but their values were still in the lower normal range and were classified as undefined. Mean diffusivity (D) maps of the entire brain were generated and D was measured with regions of interest (ROI) in the medulla, pons, middle cerebellar peduncles, and the peridentate white matter. Moreover, after exclusion of the skull with manual segmentation and of the CSF with application of a threshold value, histograms were obtained for D of the brainstem and cerebellum and for D of the cerebral hemispheres. As compared to controls, a (P < 0.001) increase of D was observed in the medulla, middle cerebellar peduncles, and peridentate white matter in OPCA and undefined patients groups who had also significantly increased values of the 25th and 50th percentiles in the brainstem and cerebellum D histogram. In CCA (P = 0.01), an increase of the 25th and 50th percentile of the D value was observed in the brainstem and cerebellum histograms. The SA group showed (P < 0.001) an increased D in the medulla only. A correlation between clinical severity as assessed with the Inherited Ataxias Clinical Rating Scale (IACRS) and the 50th percentile of the D value in the brainstem and cerebellum histogram (r = 0.69) was observed in patients with SCA1 or SCA2. Diffusion MR imaging reveals variable patterns of increase of D in the brainstem, cerebellum, and cerebral hemispheres in degenerative ataxias that match the known distribution of the neuropathological changes.

Whole brain apparent diffusion coefficient histogram: a new tool for evaluation of leukoaraiosis.

To test whole brain apparent diffusion coefficient histogram analysis as an alternative approach to visual score for the assessment of leukoaraiosis (LA).

Brain structural damage in spinocerebellar ataxia type 2. A voxel-based morphometry study

Voxel‐based morphometry (VBM) enables an unbiased in‐vivo whole‐brain quantitative analysis of differences in gray matter (GM), white matter (WM) and cerebro‐spinal fluid (CSF) volumes. We assessed with VBM 20 spinocerebellar ataxia Type 2 (SCA2) patients with mild or moderate cerebellar deficit and 20 age and sex‐matched healthy controls. SCA2 patients showed a significant (P < 0.05 corrected for multiple comparison) symmetric loss of GM in the cerebellar vermis and hemispheres sparing lobules I,II, Crus II,VII, and X, and of the WM in the peridentate region, middle cerebellar peduncles, dorsal pons, and cerebral peduncles. The CSF volume was increased in the posterior cranial fossa. No GM, WM or CSF volume changes were observed in the supratentorial compartment. A mild (P < 0.05, >0.01) correlation was observed between the GM and WM loss and severity of the neurological deficit. In SCA2 patients with mild to moderate cerebellar deficit, GM and WM volume loss and CSF volume increase are confined to the posterior cranial fossa.

Adult Alexander's disease without leukoencephalopathy

poison control center consultation. Tamoxifen infrequently causes reversible neurotoxicity, but only at much higher doses ( 160mg/m daily). Recent investigations into the use of artemisinin compounds in cancer treatment have not been substantiated in clinical trials. Because of pervasive reports of animal brainstem toxicity, and the gradual emergence of similar patient cases, it becomes imperative to ascertain the safety of prolonged courses of artemisinin for cancer prophylaxis.

Combining functional and structural brain magnetic resonance imaging in Huntington disease.

Objective: To concurrently investigate with magnetic resonance (MR) the brain activation and regional brain atrophy in patients with Huntington disease (HD). Methods: Nine symptomatic HD patients and 11 healthy subjects underwent an MR study including functional MR acquisition during finger tapping of the right hand and high-resolution T1-weighted images. Functional and structural data were analyzed using Statistical Parametric Mapping 2 software. Results: As compared with control subjects, HD patients showed decreased activation in the left caudate nucleus and medial frontal and anterior cingulate gyri and increased activation in the right supplementary motor area and supramarginal gyrus and left intraparietal sulcus. The pattern of atrophy included thinning of the gray matter (GM) in the insula, inferior frontal gyrus, caudate, lentiform nucleus, and thalamus, bilaterally, in the left middle frontal, middle occipital, and middle temporal gyri, and of periventricular, subinsular, right temporal lobe, and left internal capsule white matter. Only the decreased activation in the caudate nucleus correlated topographically with the caudate GM loss. Conclusion: The cortical areas of functional changes do not correspond to those of GM atrophy in patients with HD and are likely to reflect decreased output of the motor basal ganglia-thalamo-cortical circuit and compensatory recruitment of accessory motor pathways.

Impact of cerebrospinal fluid contamination on brain metabolites evaluation with 1H-MR spectroscopy: A single voxel study of the cerebellar vermis in patients with degenerative ataxias

To investigate the impact of cerebrospinal fluid (CSF) contamination on metabolite evaluation in the superior cerebellar vermis with single‐voxel 1H‐MRS in normal subjects and patients with degenerative ataxias.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreichs ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor‐sensory tasks of different complexity, i.e. continuous hand tapping and writing of “8” figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age‐matched healthy controls were recruited. Task execution was monitored and recorded using MR‐compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the “8” by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory‐motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo‐activation during hand tapping. During writing of the “8” task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the “8” increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance. Hum Brain Mapp, 2012.