Placido Bramanti

Diffuse structural and metabolic brain changes in Fabry disease.

AbstractObjectivesTo assessnstructural and metabolic brainnchanges in subjects affected bynFabry disease (FD) or carrying thendisease mutation.BackgroundFDnis an X–linked metabolic disorderndue to α-galactosidase A deficiency,nwhich leads to storage ofnglycosphingolipids in many tissuesnand organs. Previous MR studiesnhave shown structural and metabolicnbrain abnormalities in FD patients.nIt is not clear, however,nwhether tissue damage can be seennin both the brains of hemizygousnand heterozygous and whethernquantitative MR metrics are usefulnto monitor disease evolution.Design/MethodsWe studied 4nmales and 4 females with FD. Eachnsubject underwent brain protonnMRI/MR spectroscopic imagingn(MRSI) examinations to obtainnmeasures of total brain volumes,ntotal brain lesion volumes, magnetizationntransfer ratios (MTr) innWM and central brain levels ofnN–acetylaspartate (NAA) to creatinen(Cr). A second MR examinationnwas performed in five subjectsnafter 2 years.ResultsFocal WMnlesions were found in 2 males and 1nfemale. The MTr values were alwaysnlow in the WM lesions of FD subjectsn(p < 0.001) and also were lownin the normal–appearing WM of 2naffected males. Total brain volumesnwere never decreased in FD subjects.nBrain NAA/Cr values werensignificantly (p = 0.005) lower innFD subjects than in normal controlsnand correlated closely withnRankin scale measures (r = –0.79).nOn follow–up examinations, no significantnMR changes were found.nHowever, the small changes innNAA/Cr correlated closely withnchanges in Rankin scoresn(r = –0.86).ConclusionsSubtlenstructural and metabolic tissuendamage can extend beyond WMnlesions in FD subjects. Diffusenbrain NAA/Cr decrease can benfound in FD subjects in relation tonthe degree of their CNS involvementnand its evolution over time.

Multiparametric MR investigation of the motor pyramidal system in patients with 'truly benign' multiple sclerosis

One possible explanation for the mismatch between tissue damage and preservation of neurological functions in patients with benign multiple sclerosis (BMS) is that the pathophysiology differs from that occurring in other multiple sclerosis (MS) phenotypes. The objective of this study was to identify pathologically specific patterns of tissue integrity/damage characteristics of patients with BMS, and markers of potential prognostic value. The pyramidal system was investigated in 10 BMS patients and 20 controls using voxel-based morphometry to assess grey matter (GM) atrophy, and diffusion tractography and quantitative magnetization transfer to quantify the microstructural damage in the corticospinal tracts (CSTs). Widespread reductions in GM volume were found in patients compared with controls, including the primary motor cortex. A significant decrease was observed in the mean macromolecular pool ratio (F) of both CSTs, with no fractional anisotropy (FA) change. GM volume of the primary motor areas was associated with clinical scores but not with the CST parameters. The mismatch between F and FA suggests the presence of extensive demyelination in the CSTs of patients with BMS, in the absence of axonal damage. The lack of correlation with GM volume indicates a complex interaction between disruptive and reparative mechanisms in BMS.

Assessment of nociceptive system in vegetative and minimally conscious state by using laser evoked potentials

Abstract Primary objective: The aim of this study is to assess if laser evoked potentials (LEPs) examination should be considered as an objective evidence of potential or residual pain perception capacity in vegetative (VS) and minimally conscious state (MCS) patients and if it could be a feasible methodology in order to differentiate these two clinical entities. Research design: This is a cross-sectional observational study focusing on the role of LEP examination, which is an easy and objective neurophysiological approach of the nociceptive system. Methods and procedures: Thirteen VS and 10 MCS patients were enrolled. All subjects were evaluated clinically by using validated behavioural scales and underwent to upper and lower limbs LEP recording. Main outcomes and results: Intra-group LEPs analysis in VS patients highlighted significant differences for N2P2 latency (pu2009=u20090.036) and amplitude (pu2009=u20090.018). Inter-group LEPs analysis showed significant differences in post-anoxic condition for N2P2 latency (pu2009=u20090.034), amplitude (pu2009=u20090.034) and a trend in N2P2 latency in brain trauma (pu2009=u20090.07). Interestingly, correlation analysis showed a significant relationship between N2P2 amplitude and Coma Recovery Scale-Revised scoring in the post-traumatic VS (ru2009=u20090.823, pu2009=u20090.044). Conclusions: The findings lead to detection of potential markers of conscious pain perception in patients with DOC, with important impact on therapeutic and rehabilitative management, and provide new information that may allow a better differential diagnosis.

Prominent brain axonal damage and functional reorganization in “pure” adrenomyeloneuropathy

Background: Cerebral involvement is usually absent in pure adrenomyeloneuropathy (AMN). Recently, nonconventional MR studies have reported brain abnormalities in patients with pure AMN, providing evidence that occult cerebral involvement may occur in this disease. It remains unclear, however, whether these brain abnormalities reflect centripetal extension of spinal cord long-tract axonopathy or can be the expression of a pathologic process largely involving the brain. Methods: Conventional MRI and proton MR spectroscopic imaging (1H-MRSI) data of four patients with pure AMN were compared to those of four men with spinal cord injury (SCI) and 10 age-matched healthy men (HM). Resonance intensity areas of N-acetylaspartate (NAA) and choline were calculated as ratios to creatine (Cr) in voxels located in white matter (WM) regions. Functional MRI (fMRI) data during simple motor task were obtained in a separate session in three patients with AMN and three age-matched HM. Results: Conventional MRI examinations were normal in all patients. On 1H-MRSI, NAA/Cr values were lower in all WM regions of patients with AMN than in those of patients with SCI (p < 0.05) and HM (p < 0.01). In contrast, patients with SCI showed NAA/Cr values lower than HM only in the periventricular WM (p = 0.04). At fMRI, patients with AMN showed a more pronounced activation than HM in all movement-associated cortical regions contralateral to the hand moved and an exclusive voxel activation of the primary motor, somatosensory, and posterior parietal cortices ipsilateral to the hand moved. Conclusions: CNS damage in pure adrenomyeloneuropathy is not confined exclusively to spinal cord and seems to primarily involve the brain. GLOSSARY: 1H-MRSI = proton MR spectroscopic imaging; AC = anterior commissure; AMN = adrenomyeloneuropathy; BOLD = blood oxygenation level dependent; BR = brisk reflexes; Cho/Cr = choline to creatine ratio; Cr = creatine; DTI = diffusion tensor imaging; EA = endocrine abnormalities; FLAIR = fluid-attenuated inversion recovery; fMRI = functional MRI; FMRIB = Functional Magnetic Resonance Imaging of the Brain; FILM = FMRIB’s improved linear model; Fr-WM = frontal WM; HM = healthy men; Lac = lactate; MD = motor deficits; NAA = N-acetylaspartate; Naa/Cr = N-acetylaspartate to creatine ratio; PC = posterior commissure; PD = proton density; Post-WM = deep posterior WM; Pv-WM = periventricular WM; SA = sensory abnormalities; SCI = spinal cord injury; SP = spastic paraparesis; Sph Dis = sphincteric disturbances; VLCFA = very-long-chain fatty acids; VOI = volume of interest; WM = white matter.

Snake Segmentation of Multiple Sclerosis Lesions for Assisted Diagnosis by Cluster Analysis-Based Techniques

Magnetic Resonance Imaging (MRI), allowing in-vivo detection of lesions, is today a crucial tool for diagnosis of Multiple Sclerosis (MS). Although the detection of lesions are not sufficient for a diagnosis of MS because of similarity with patterns detected in other neurological diseases, taking into account different radiological informations, MRI findings can often yield a high degree of confidence. We used a snake based procedure for segmentation of lesion then proposing a method based on Cluster Analysis to support clinicians in the diagnosis of MS. By identifying a minimum set of significant descriptors, our algorithm can help neurologist and neuroimaging expert to distinguish MS plaques from other kinds of lesions.

Cortical reorganization in multiple sclerosis after intrathecal baclofen therapy

Our objective was to assess the role of Intrathecal Baclofen Therapy (ITB) in the cortical reorganization in a patient affected by multiple sclerosis (MS) undergoing physical therapy. We reported a case of a woman affected by MS and severe spasticity, who performed an fMRI examination, before and after the ITB implantation. The subject showed controlateral motor cortex activation after motor task. After a month of ITB implantation, patient showed ipsilateral and controlateral motor cortex activation although with a broader extension. fMRI examination supported the hypothesis of a central influence in patients who undergo physiotherapy and therapy with ITB.

Neuroimaging and Outcome Assessment in Vegetative and Minimally Conscious State

Consciousness is a multifaceted concept that has two dimensions: arousal, or wakefulness (i.e., level of consciousness), and awareness (i.e., content of consciousness) (Laureys et al., 2004). An accurate and reliable assessment of the arousal and awareness of consciousness in patients with severe brain damage is of greatest importance for the differential diagnosis of low levels consciousness patients and for outcome evaluation. Following coma, some patients permanently lose all brainstem function (brain death), some progress to “wakeful unawareness” (vegetative state VS), whereas others recover typically and progress through different stages before fully or partly recovering consciousness (minimally conscious state MCS). Patients in VS can open their eyes and exhibit basic orienting responses, but show no conscious, purposeful activity. Reflex and other movements are seen, mediated by brainstem, spinal cord, and brainstem-diencephalic arousal systems (Laureys et al., 2004). VS can occur after patients emerge from an acute catastrophic brain insult causing coma, or can also be seen in degenerative or congenital nervous system disorders. The two common findings are necrosis of the cerebral cortex, thalamus and brainstem (usually after anoxic injury) and diffuse axonal injury (usually after trauma), although other pathological findings can be seen in degenerative and other disorders (Laureys, 2008). The MCS patients do not meet diagnostic criteria for coma or VS because they demonstrate some inconsistent but clear evidence of consciousness (Laureys et al., 2008; Giacino et al., 2002). In the MCS, there is variable impaired function of the cerebral cortex, diencephalons and upper brainstem. This allows occasional conscious behaviours to occur, unlike in VS or coma. Patients may enter the MCS as they emerge from coma or VS, or they can become minimally conscious as a result of acute injury or chronic degenerative diseases. Recent studies suggest a number of potential clinical and rehabilitative applications of magnetic resonance (MR) techniques. Although bedside clinical examination remains the criterion standard for establishing diagnosis, MR may provide an adjunctive diagnostic role when behavioural findings are very limited or ambiguous. The future of diagnostic and prognostic assessment of patients with disorders of consciousness (DOC) envisions a battery of neurobehavioral and neuroimaging techniques (such as structural and functional MR imaging (MRI and

Early Marker for the Diagnosis of Parkinson's Disease

Parkinson’s disease (PD) is a progressive disorder with a relentless neuronal cell loss in several brain areas and nuclei notably in the substantia nigra (SN). The course of this neuronal loss is still unclear and may be highly variable in different PD patients and at different phases of the disease. At present, no treatment has proven to influence this progressive course of the disease by protecting neurons or by postponing cell death. One potential reason for the lack of neuroprotective effects of various agents, which have been highly effective in animal experiments, is the fact that the neurodegenerative process has already substantially proceeded when the diagnosis is established on the basis of widely accepted diagnostic criteria for PD: when the patients fulfill the clinical criteria of PD, 60– 70% of neurons of the SN are degenerated and the striatal dopamine content is reduced by 80%, suggesting that the remaining neurons of the SN are also altered. The “preclinical” phase may give the incorrect impression of patients exhibiting no clinical signs or symptoms of the incipient disease. Conversely, it is known that motor signs develop insidiously and minor signs of asymmetric hypokinesia may be detected years before the diagnosis of PD can be established. In addition, non-motor symptoms such as mood disorders, olfactorial, vegetative, sensory or neuropsychological signs may be noticed by the patients or physicians in advance of motor signs reflecting the dysfunction of dopaminergic or non-dopaminergic neurons. Therefore, the term “early” or “prediagnostic” phase of PD would more appropriately characterize this stage of the disease. The clinical impression of autonomic, olfactorial and affective symptoms preceding motor signs of PD are in line with the findings demonstrating that neuronal alteration, with regard to Lewy body formation, occurs first in the dorsal vagal nucleus, the olfactory bulb, the raphe and coeruleus nuclei before entering the SN. According to neuropathological findings, it is suggested that approximately 10% of subjects older than 60 years are in the “prediagnostic” phase of PD. These subjects exhibit the pathological hallmarks of PD, like Lewy bodies and neuronal loss at the SN, without showing the motor signs during life time that allow the diagnosis of PD. In only 10% of this group with so-called “incidental Lewy body disease”, neuronal loss will proceed reaching the degree where motor symptoms are distinct enough to allow the diagnosis of PD.