Claudio Colonnese

Morphological and Functional Characteristics of Patent Foramen Ovale and Their Embolic Implications

Background and Purpose Transesophageal echocardiography (TEE) has detected a high prevalence of patent foramen ovale (PFO) in stroke patients, but the clinical implications of the distinctive characteristics of this patency are still a matter of debate. Methods We studied 350 patients with acute ischemic stroke or transient ischemic attack (TIA) within 1 week of admission. Of these, 101 (29%) were identified by contrast TEE to have a PFO; 86 patients (25%) were cryptogenic stroke patients, and 163 were excluded because of the presence of a definite or possible arterial or clinical evidence of a source of emboli or small-vessel disease. Thirteen PFO subjects without a history of embolism were designated as the control group. All PFO and cryptogenic stroke patients were followed up by neurological visits. Results Compared with controls, PFO patients with acute stroke or TIA more frequently presented with a right-to-left shunt at rest and a higher membrane mobility (P <0.05). Patients with these characteristics were considered to be at high risk. During a median follow-up period of 31 months (range, 4 to 58 months), 8 PFO and 18 cryptogenic stroke patients experienced recurrent cerebrovascular events. The cumulative estimate of risk of cerebrovascular event recurrence at 3 years was 4.3% (95% confidence interval [CI], 0% to 10.2%) for “low-risk” PFO patients, 12.5% (95% CI, 0% to 26.1%) for “high-risk” PFO patients, and 16.3% (95% CI, 7.2% to 25.4%) for cryptogenic stroke patients (high-risk PFO versus low-risk PFO, P =0.05). Conclusions The association of right-to-left shunting at rest and high membrane mobility, as detected by contrast TEE, seems to identify PFO patients with cerebrovascular ischemic events who are at higher risk for recurrent brain embolism.

Emilin1 links TGF-β maturation to blood pressure homeostasis

TGF-beta proteins are main regulators of blood vessel development and maintenance. Here, we report an unprecedented link between TGF-beta signaling and arterial hypertension based on the analysis of mice mutant for Emilin1, a cysteine-rich secreted glycoprotein expressed in the vascular tree. Emilin1 knockout animals display increased blood pressure, increased peripheral vascular resistance, and reduced vessel size. Mechanistically, we found that Emilin1 inhibits TGF-beta signaling by binding specifically to the proTGF-beta precursor and preventing its maturation by furin convertases in the extracellular space. In support of these findings, genetic inactivation of Emilin1 causes increased TGF-beta signaling in the vascular wall. Strikingly, high blood pressure observed in Emilin1 mutants is rescued to normal levels upon inactivation of a single TGF-beta1 allele. This study highlights the importance of modulation of TGF-beta availability in the pathogenesis of hypertension.

Hyperdense middle cerebral artery CT sign

SummaryThe early CT finding of an hyperdensity of a portion of the middle cerebral artery Hyperdense Middle Cerebral Artery Sign (HMCAS), in patients with supratentorial stroke, is often indicative of an embolic occlusion. Aim of this study was to verify the incidence and reliability of the HMCAS and its possible correlation with early CT findings and with the extent of late brain damage. We studied 36 patients presenting with symptoms of stroke in the MCA territory, by means of CT and angiography performed respectively within 4 and 6 hours. Follow-up CT scans were then obtained after one week and three months from the ischemic event. The HMCAS was present in 50% of our patients and in this group it always correlated positively with the angiographic finding of occlusion. The same group presented a high incidence of erly CT hypodensity (88%). Finally the presence of HMCAS might be considered a negative prognostic sign for the development of extensive brain damage.

Use of Bacille Calmette–Guèrin (BCG) in multiple sclerosis

We studied the effect of Bacille Calmette-Guerin (BCG) vaccine as an immunomodulator in MS. According to the guidelines for clinical trials in MS, a single crossover, MRI-monitored trial was performed in 14 patients with relapsing-remitting MS. After treatment, MRI activity was significantly reduced. No major adverse effects were reported. Adjuvant therapy with BCG vaccine was safe and merits study in MS.

Correlation between MRI findings and long-term outcome in patients with severe brain trauma

Abstract Our aim was to relate MRI findings in patients with severe traumatic brain injury (TBI) to clinical severity and long-term outcome. We studied 37 patients with severe TBI, who were submitted to clinical assessment for disability and cognition and to MRI 60–90 days after trauma. Clinical assessment was also performed 3, 6 and 12 months later. The number and volume of lesions in various cerebral structures were calculated semiautomatically from FLAIR and fast field-echo images. Possible correlations between total and regional lesion volume and clinical deficits were then investigated. The frontal and temporal lobes were most frequently involved. Total lesion volume on FLAIR images correlated significantly with clinical outcome, whereas that on FFE images did not. Regional analysis showed that FLAIR lesion volume in the corpus callosum correlated significantly with scores on disability and cognition scales at the first clinical assessment. FLAIR lesion volume in the frontal lobes correlated significantly with clinical scores 1 year later.

Distinct brain volume changes correlating with clinical stage, disease progression rate, mutation size, and age at onset prediction as early biomarkers of brain atrophy in Huntington's disease.

Searching brain and peripheral biomarkers is a requisite to cure Huntingtons disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross‐sectional and longitudinal rate of brain atrophy, quantitatively measured by fully‐automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene‐positive subjects with presymptomatic to advanced HD, and age‐matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain‐derived‐neurotrophic‐factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone‐of‐onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG‐based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R2= 0.25, P < 0.0001).

Magnetic resonance imaging in Posterior Reversible Encephalopathy Syndrome: report of three cases and review of literature

IntroductionEclampsia is one of the main causes of Posterior Reversible Encephalopathy Syndrome (PRES) a recent clinico-neuroradiological entity represented by characteristic MR findings of a symmetric bilateral subcortical/cortical hyperintensity in T2-weighted images, more often in parieto-occipital lobes, accompanied by clinical neurological alterations. Neuroradiological and clinical alterations are commonly completely reversible although ischemic evolution has been described. The pathophysiology is still a matter of debate. Specific magnetic resonance (MR) techniques, such as FLAIR (fluid attenuated inversion recovery) and DWI (diffusion weighted images) sequences, have improved the ability to detect subcortical/cortical lesions and helped to clarify the underlying pathophysiological mechanism of cerebrovascular involvement, which results important for an appropriate therapeutic decision.Case report and discussionWe report the MR imaging findings of three patients with eclampsia and PRES as well as a careful review of literature.

Apparent diffusion coefficient obtained by magnetic resonance imaging as a prognostic marker in glioblastomas: correlation with MGMT promoter methylation status

ObjectiveTo evaluate whether apparent diffusion coefficient (ADC) values can predict the status of MGMT of glioblastoma multiforme (GBM) and correlate with overall survival (OS) and progression-free survival (PFS).MethodsThis retrospective study included 47 patients with pathologically proven glioblastoma. All of them underwent MR DWI study before surgery (mean time 1 week) and the status of methylguanine-DNA-methyltransferase (MGMT) promoter methylation was searched for. Minimum apparent diffusion coefficient (ADC) values were evaluated. OS and PSF parameters were calculated, and Student’s t-test, Kaplan-Meier curves, linear and Cox regression were performed.ResultsTwenty-five patients showed positive methylation of the MGMT promoter. Patients showing MGMT promoter methylation had higher minimum ADC values, and they survived longer than those without MGMT promoter methylation. The median ADCmin value of 0.80 represents the cutoff value able to distinguish between methylated and un-methylated patients. Patients showing minimum ADC values higher than 0.80 survived longer than patients with minimum ADC values lower than 0.80. A linear correlation between minimum ADC values vs. the OS and PFS was observed.ConclusionsMinimum ADC values in glioblastoma multiforme could be used as a preoperative parameter to estimate the status of MGMT promoter methylation and the survival of patients.Key Points• Diffusion-weighted MR imaging (DWI) provides new insights into glioblastoma multiforme (GBM)• DWI ADCmin values can predict the methylation status of MGMT promoter.• The MGMT promoter methylation group survived longer than the unmethylated group.• Patients with high ADCmin values survived longer than patients with low values.

A rapid and reliable procedure to localize subdural electrodes in presurgical evaluation of patients with drug-resistant focal epilepsy

OBJECTIVES To evaluate a novel method for localization of subdural electrodes in presurgical assessment of patients with drug-resistant focal epilepsy. METHODS We studied eight consecutive patients with posterior epilepsy in whom subdural electrodes were implanted for presurgical evaluation. Electrodes were detected on post-implantation brain CT scans through a semiautomated procedure based on a MATLAB routine. Then, post-implantation CT scans were fused with pre-implantation MRI to localize the electrodes in relation to the underlying cortical structures. The reliability of this procedure was tested by comparing 3D-rendered MR images of the electrodes with electrode position as determined by intraoperative digital photography. RESULTS In each patient, all electrodes could be correctly localized and visualized in a stereotactic space, thus allowing optimal surgery planning. The agreement between the procedure-generated images and the digital photographs was good according to two independent raters. The mean mismatch between the 3D images and the photographs was 2 mm. CONCLUSIONS While our findings need confirmation on larger samples including patients with anterior epilepsy, this procedure allowed to localize subdural electrodes and to establish the spatial relationship of each electrode to the underlying brain structure, either normal or damaged, on brain convessity, basal and medial cortex. SIGNIFICANCE Being simple, rapid, unexpensive, and reliable, this procedure holds promise to be useful to optimize epilepsy surgery planning.

Gilles de la Tourette syndrome and voluntary movement: A functional MRI study

Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization of movement control. The aim of this study was to use functional magnetic resonance imaging to study motor cortex activation in a TS patient. Usual and unusual self-paced voluntary movements were performed. The TS patient displayed supplementary motor area (SMA) activation during both tasks. This activation reflects a continuous use of the SMA to perform the voluntary motor movements required in both tasks. Moreover, the absence of tics during the execution of these voluntary motor tasks suggests that tic activity may be suppressed by additional mental effort.