Mirco Cosottini

Silent Cerebral Ischemia Detected With Diffusion-Weighted Imaging in Patients Treated With Protected and Unprotected Carotid Artery Stenting

Background and Purpose— Percutaneous transluminal angioplasty with stent (CAS) is an alternative method to endarterectomy in the revascularization of carotid artery stenosis. Protected CAS is currently used to prevent distal embolization. Diffusion-weighted MRI (DWI) is the most sensitive tool to evaluate silent cerebral ischemia. The purpose of this research was to assess the incidence of cerebral embolic lesions during CAS and to evaluate whether cerebral protection devices can reduce the number of silent cerebral ischemia with respect to unprotected CAS. Methods— Fifty-two patients with high-grade internal stenosis underwent CAS; 30 patients (group a) were treated with a cerebral protection device, and 22 (group b) were treated without it. All of the patients were evaluated preoperatively and postoperatively with fluid-attenuated inversion recovery and DWI sequences to depict the number of new embolic silent cerebral lesions. Results— Embolic silent cerebral lesions occurred in 30% of CAS. Cerebral protection devices reduce the number of new lesions significantly reducing the consistent lesions ipsilateral to the treated vessel. Inconsistent lesions do not differ in both groups of patients. Clinical, radiological, and procedural variables do not correlate with the appearance of new cerebral lesions. Conclusions— Embolic cerebral lesions detected with DWI are more frequent with unprotected CAS, although they are present also with the use of cerebral protection devices. Probably a part of silent cerebral lesions arise from the procedural maneuver in the aortic arch.

The Present and the Future of Neuroimaging in Amyotrophic Lateral Sclerosis

SUMMARY: In patients with ALS, conventional MR imaging is frequently noninformative, and its use has been restricted to excluding other conditions that can mimic ALS. Conversely, the extensive application of modern MR imaging−based techniques to the study of ALS has undoubtedly improved our understanding of disease pathophysiology and is likely to have a role in the identification of potential biomarkers of disease progression. This review summarizes how new MR imaging technology is changing dramatically our understanding of the factors associated with ALS evolution and highlights the reasons why it should be used more extensively in studies of disease progression, including clinical trials.

Contrast-Enhanced Three-Dimensional Magnetic Resonance Angiography of Atherosclerotic Internal Carotid Stenosis as the Noninvasive Imaging Modality in Revascularization Decision Making

Background and Purpose— In patients with severe internal carotid artery stenoses, thromboendarterectomy significantly reduces both ischemic stroke and the risk of more ischemic attacks. Digital subtraction angiography (DSA) is the accepted preoperative test to determine whether a high-grade stenosis is present and requires surgical therapy. However, DSA has a procedural risk of stroke between 0.7% and 1%. An accurate, noninvasive imaging protocol with no risk of severe complications would significantly increase the benefit of surgical treatment. The aims of the study were (1) to evaluate the diagnostic accuracy of contrast-enhanced magnetic resonance angiography (CEMRA) in detecting and grading internal carotid artery stenoses and (2) to assess the misclassification rate of vessels suitable for revascularization by CEMRA. Methods— Ninety-two patients with sonographic evidence of neck vessel stenosis were enrolled in the study. All patients were submitted to CEMRA and DSA. CEMRA images were evaluated for the presence of mild, moderate, or severe stenosis and occlusion. Results— Sensitivity, specificity, and diagnostic accuracy were 97%, 82%, and 92.5%, respectively. Agreement with DSA was optimal at &kgr;=0.87. The misclassification rate of CEMRA was 3.1% because of its tendency to overestimate the stenosis. Conclusions— The high diagnostic accuracy and limited misclassification rate suggest that CEMRA can be considered a powerful tool for the preoperative, noninvasive evaluation of atherosclerotic pathology of carotid arteries.

Diagnostic methods and treatment options for focal cortical dysplasia.

Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)–functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high‐frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high‐field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose–positron emission tomography (FDG‐PET) is highly sensitive for detecting FCD in MRI‐negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment‐resistant cases, initial evidence from novel approaches suggests that future success is possible.

MR Imaging of the Substantia Nigra at 7 T Enables Diagnosis of Parkinson Disease

PURPOSE To evaluate the anatomy of the substantia nigra (SN) in healthy subjects by performing 7-T magnetic resonance (MR) imaging of the SN, and to prospectively define the accuracy of 7-T MR imaging in distinguishing Parkinson disease (PD) patients from healthy subjects on an individual basis. MATERIALS AND METHODS The 7-T MR imaging protocol was approved by the Italian Ministry of Health and by the local competent ethics committee. SN anatomy was described ex vivo on a gross brain specimen by using highly resolved proton-density (spin-echo proton density) and gradient-recalled-echo (GRE) images, and in vivo in eight healthy subjects (mean age, 40.1 years) by using GRE three-dimensional multiecho susceptibility-weighted images. After training on appearance of SN in eight healthy subjects, the SN anatomy was evaluated twice by two blinded observers in 13 healthy subjects (mean age, 54.7 years) and in 17 PD patients (mean age, 56.9 years). Deviations from normal SN appearance were described and indicated as abnormal, and both diagnostic accuracy and intra- and interobserver agreement for diagnosis of PD with 7-T MR imaging were calculated. RESULTS Three-dimensional multiecho susceptibility-weighted 7-T MR imaging reveals a three-layered organization of the SN allowing readers to distinguish pars compacta ventralis and dorsalis from pars reticulata. The abnormal architecture of the SN allowed a discrimination between PD patients and healthy subjects with sensitivity and specificity of 100% and 96.2% (range, 92.3%-100%), respectively. Intraobserver agreement (κ = 1) and interobserver agreement (κ = 0.932) were excellent. CONCLUSION MR imaging at 7-T allows a precise characterization of the SN and visualization of its inner organization. Three-dimensional multiecho susceptibility-weighted images can be used to accurately differentiate healthy subjects from PD patients, which provides a novel diagnostic opportunity.

Assessment of midbrain atrophy in patients with progressive supranuclear palsy with routine magnetic resonance imaging

Objectives –  To assess midbrain atrophy through morphometric (linear, surface and volumetric) measurements in patients with clinically diagnosed progressive supranuclear palsy (PSP) and to establish the most accurate measure to be implemented in routine magnetic resonance (MR) protocol in distinguishing PSP from healthy subjects and MSA‐p (multiple system atrophy, parkinsonian form) patients.

Brainstem involvement in Unverricht–Lundborg disease (EPM1): An MRI and 1H MRS study

Abstract—MRI of the brain and proton MRS (1H MRS) of the pons and dentate were obtained in 10 patients with genetically confirmed Unverricht–Lundborg disease (EPM1) and 20 control subjects. Patients with EPM1 showed (p ≤ 0.01) loss of bulk of the basis pontis, medulla, and cerebellar hemispheres. Cerebral atrophy was present in six patients. The N-acetylaspartate/creatine and choline/creatine ratios were reduced in the pons but not in the dentate (p ≤ 0.005). Brainstem involvement could play a role in pathophysiology of EPM1.

Diagnostic accuracy of diffusion tensor imaging in amyotrophic lateral sclerosis: A systematic review and individual patient data meta-analysis

RATIONALE AND OBJECTIVES There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966-April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66-0.83), pooled sensitivity was 0.68 (95% CI: 0.62-0.75), and pooled specificity was 0.73 (95% CI: 0.66-0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended cortical damage within the motor circuit of ALS patients. The functional changes in non-primary motor cortices pertaining to fronto-parietal circuit suggest an over-recruitment of a pre-existing physiological sensory-motor network. However, the concomitant fronto-parietal cortical atrophy arises the possibility that such a hyper-activation reflects cortical hyper-excitability due to loss of inhibitory inter-neurons.

Parkinson's Disease and pathological gambling: Results from a functional MRI study†

Seven patients with a diagnosis of Parkinsons disease (PD) and pathological gambling (PG) and 7 PD patients without PG were investigated by functional MRI and a block‐design experiment with gambling‐related visual cues alternating with neutral stimuli and rest periods. Compared with PD/non‐PG, in PD/PG patients, several areas of increased cue‐related blood oxygen level dependent (BOLD)‐response were observed including bilateral anterior cingulate cortex, medial and superior frontal gyri, and precuneus, right inferior parietal lobule, and ventral striatum. The over activation of cingulate cortex and ventral striatum in PD/PG patients after the craving task is similar to that reported in addicted patients, whereas the activation of the parietal structures is probably related to the attentional network.