Radiological classification of dementia from anatomical MRI assisted by machine learning-derived maps.

BACKGROUND AND PURPOSE: Many artificial intelligence tools are currently being developed to assist diagnosis of dementia from magnetic resonance imaging (MRI). However, these tools have so far been difficult to integrate in the clinical routine workflow. In this work, we propose a new simple way to use them and assess their utility for improving diagnostic accuracy. MATERIALS AND METHODS: We studied 34 patients with early-onset Alzheimer's disease (EOAD), 49 with late-onset AD (LOAD), 39 with frontotemporal dementia (FTD) and 24 with depression from the pre-existing cohort CLIN-AD. Support vector machine (SVM) automatic classifiers using 3D T1 MRI were trained to distinguish: LOAD vs. Depression, FTD vs. LOAD, EOAD vs. Depression, EOAD vs. FTD. We extracted SVM weight maps, which are tridimensional representations of discriminant atrophy patterns used by the classifier to take its decisions and we printed posters of these maps. Four radiologists (2 senior neuroradiologists and 2 unspecialized junior radiologists) performed a visual classification of the 4 diagnostic pairs using 3D T1 MRI. Classifications were performed twice: first with standard radiological reading and then using SVM weight maps as a guide. RESULTS: Diagnostic performance was significantly improved by the use of the weight maps for the two junior radiologists in the case of FTD vs. EOAD. Improvement was over 10 points of diagnostic accuracy. CONCLUSION: This tool can improve the diagnostic accuracy of junior radiologists and could be integrated in the clinical routine workflow.

COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps.

BACKGROUND: COL4A3, COL4A4, and COL4A5 are the only collagen genes that have been implicated in inherited nephropathies in humans. However, the causative genes for a number of hereditary multicystic kidney diseases, myopathies with cramps, and heritable intracranial aneurysms remain unknown. METHODS: We characterized the renal and extrarenal phenotypes of subjects from three families who had an autosomal dominant hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC), which we propose is a syndrome. Linkage studies involving microsatellite markers flanking the COL4A1-COL4A2 locus were performed, followed by sequence analysis of COL4A1 complementary DNA extracted from skin-fibroblast specimens from the subjects. RESULTS: We identified three closely located glycine mutations in exons 24 and 25 of the gene COL4A1, which encodes procollagen type IV alpha1. The clinical renal manifestations of the HANAC syndrome in these families include hematuria and bilateral, large cysts. Histologic analysis revealed complex basement-membrane defects in kidney and skin. The systemic angiopathy of the HANAC syndrome appears to affect both small vessels and large arteries. CONCLUSIONS: COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps.

Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain.

The COL4A1 gene encodes the α1-chain of type IV collagen, which is ubiquitously expressed in basement membranes. Mutations in COL4A1 have been reported in autosomal-dominant porencephaly and in patients with symptomatic small vessel brain disease, inconstantly associated with eye defects. We have previously reported three COL4A1 mutations associated with a systemic phenotype that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps). We carried out a clinical and genetic study of three families presenting with characteristic features of HANAC syndrome. Common systemic signs included arterial retinal tortuosity and muscle cramps, with a variable combination of small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel COL4A1 missense substitutions are described, which affect highly conserved glycine residues within the collagenous domain of the protein. All six known mutations associated with the HANAC phenotype are localized within the CB3[IV] fragment of COL4A1, which encompasses major integrin-binding sites. Our results confirm that HANAC syndrome is a distinct clinical entity within the COL4A1-related disorders, which is characterized by systemic involvement and usually asymptomatic brain disease. The restricted distribution of COL4A1 mutations within the CB3[IV] region is a characteristic of the reports of patients with HANAC, which suggests that abnormal cell-type IV collagen interactions may underlie the systemic defects observed in this syndrome.

Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity.

Objective: To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials. Methods: We analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 patients with acute IS less than 6 hours before admission and compared them with 22 age-matched healthy controls. Results: Our results demonstrated continuous basal hyperactivation of circulating neutrophils during acute IS, characterized by lower l-selectin expression and higher CD11b expression at the cell surface, increased ROS production by neutrophils, and greater circulating levels of neutrophil elastase. Neutrophil hyperactivation was associated with deregulation of the equilibrium between apoptotic and necrotic. Patients also had higher percentages than controls of the overactive senescent (CXCR4bright/CD62Ldim) neutrophil subset and increased percentage of neutrophils with a reverse transendothelial migration (CD54highCXCR1low) phenotype. Importantly, neutrophil alterations were associated with the clinical severity of the stroke, evaluated by its NIH Stroke Scale score. Conclusion: Altogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both.

Limitations of computed tomographic angiography in the diagnosis of brain death.

OBJECTIVE: To evaluate the accuracy of cerebral computed tomographic angiography (CT-a) for the diagnosis of brain death (BD). DESIGN AND SETTING: Prospective observational study in intensive care units. PATIENTS: Twenty-one clinically BD patients enrolled over 12 months. MEASUREMENTS AND RESULTS: All clinically BD patients were evaluated by electroencephalography (EEG) and CT-a after exclusion of hypothermia and drug intoxication. Data collected included: demographic characteristics, cause of BD, delay between in-hospital admission and BD diagnosis and between EEG and CT-a, occurrence of cardiac arrest, administration of vasoactive agents, results of EEG and CT-a. We evaluated the sensitivity of EEG and CT-a and their agreement. Groups were compared according to BD diagnosis by EEG and CT-a (E+C+), or only by EEG (E+C(-)). Statistical analysis were performed by Mann-Whitney test and Fisher's exact test. BD was confirmed by EEG in all cases (sensitivity 100%) whereas only 11 patients of 21 had no cerebral perfusion during CT-a (sensitivity 52.4%). No agreement was documented between EEG and CT-a for the diagnosis of BD (kappa = 0). Patients' characteristics did not differ between E+C+ and E+C(-) groups. In the E+C(-) group arterial opacification was observed in 100% of patients, but opacification of the internal cerebral veins was achieved in only 30%. CONCLUSIONS: In clinically BD patients with no electroencephalographic activity CT-a documents opacification of the intracerebral vessels in a significant percentage of the cases. Therefore CT-a cannot be recommended as a means of BD diagnosis.

Very early neurologic improvement after intravenous thrombolysis.

OBJECTIVE: To evaluate whether very early neurologic improvement (VENI) after intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) perfusion in patients with acute ischemic stroke (AIS) predicts favorable outcome at 3 months. DESIGN: Retrospective analysis of prospective data. SETTING: Stroke registry at the Stroke Unit, Tenon University Hospital. PATIENTS: We analyzed consecutive patients with AIS treated with i.v. rt-PA between November 11, 2002, and December 24, 2007. MAIN OUTCOME MEASURES: VENI at 1 hour was defined as a National Institute of Health Stroke Scale score of 0 at the end of rt-PA perfusion or an improvement of 5 or more points compared with baseline. Favorable outcome was defined as a modified Rankin Scale score of 1 or less at 3 months. RESULTS: Of 120 patients with AIS treated with i.v. rt-PA, 22 (18.3%) had VENI after i.v. rt-PA perfusion. Favorable outcome was observed in 15 patients with VENI (68.2%) and in 29 patients without VENI (29.6%) (P < .001). No symptomatic intracerebral hemorrhage occurred in patients with VENI. Mortality rates were 0% in the patients with VENI and 17.3% in patients without VENI. Baseline scores for VENI (adjusted odds ratio, 6.23; 95% confidence interval, 2.03-19.13; P = .001) and the National Institute of Health Stroke Scale (0.83; 0.76-0.91; P < .001) were the only 2 factors associated with favorable outcome (modified Rankin Scale score of ≤1). CONCLUSIONS: VENI at the end of i.v. rt-PA perfusion in patients with AIS independently predicts favorable outcome at 3 months.

Thoracic spinal cord compression indicating Wegener's granulomatosis in a patient with a previous presumptive diagnosis of microscopic polyangiitis.

Neurological signs are observed in 20-50% of cases of Wegener's granulomatosis consisting of peripheral and cranial neuropathy, and central nervous system involvement during the disease and rarely as initial symptom. We report here a case of thoracic spinal cord compression due to dural masses in a patient with a previous presumptive diagnosis of microscopic polyangiitis indicating Wegener's granulomatosis on histological examination. No other site of involvement was found. Slight clinical improvement was observed under immunosuppressive treatment probably because of spinal cord vessels lesions.

Proximal great vessels of aortic arch: comparison of three-dimensional gadolinium-enhanced MR angiography and digital subtraction angiography.

PURPOSE: To prospectively compare dynamic three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography and digital subtraction angiography (DSA) for the detection of ostial stenosis of the craniocervical vessels. MATERIALS AND METHODS: Thirty-three patients with carotid stenosis of more than 50% at sonography prospectively underwent both MR angiography and DSA. The overall quality of each DSA and MR angiographic study was analyzed. For each craniocervical vessel (brachiocephalic, common carotid, subclavian, and vertebral arteries) (n = 231), ostial stenosis was graded as follows: normal, mild (<50%), moderate to severe (>50%), or occlusion. MR angiographic and DSA results were compared by means of the Spearman rank correlation coefficient (Rs). RESULTS: The overall diagnostic quality of MR angiography was excellent or adequate. Three studies were inadequate because of a poor signal-to-noise ratio (13 of 231 arteries) or a coverage error (five of 231 arteries). Findings at MR angiography and DSA agreed on the degree of stenosis (Rs = 0.82, P <.001). No cases of stenosis of more than 50% were missed at MR angiography. However, some discrepancies were noted between vertebral arteries and the other craniocervical vessels. The sensitivity and specificity for stenosis of more than 50% in other craniocervical vessels were 100% and 98%, respectively. The sensitivity and specificity for stenosis of more than 50% in the vertebral arteries were 100% and 85%, respectively. Findings at MR angiography tended to result in overestimation of the degree of ostial stenosis, especially in vertebral arteries (10 [15%] of 66 arteries). CONCLUSION: MR angiography is useful to rule out ostial stenosis of the craniocervical vessels. MR angiography is an adequate diagnostic tool for ostial stenosis, except in the vertebral artery.