Executive dysfunctions, action slowing and their imaging correlates in early stages of Alzheimer's disease

La Maladie d'Alzheimer (MA) évolue de la plainte cognitive subjective (PCS) vers un trouble neurocognitif (TNC) mineur puis vers un TNC majeur, elle est caractérisée par un trouble mnésique proéminent. Au stade précoce de la MA, l'intensité des dysfonctions exécutives et du ralentissement de l'action (RA) ainsi que leurs corrélats anatomiques (CA) demeurent inconnus. L'objectif principal était de définir dans les phases précoces de la MA, l'intensité des dysfonctions exécutives et du RA ainsi que leurs CA. Dans l'étude 1, nous avons montré: l'atteinte des fonctions exécutives (FE) ne différait pas entre la MA (avec biomarqueurs positifs) et le TNC vasculaire. Dans l'étude 2, nous avons effectué une méta-analyse et avons montré : le temps de réaction simple (TRS) était significativement plus long dans le TNC mineur que dans le groupe control. Dans l'étude 3, nous avons montré dans la cohorte MEMENTO (2323 TNC mineurs et PCS) : l'atteinte des FE était associée à la diminution de l'épaisseur corticale dans les régions parsorbitalis gauche, supramarginale (SMG) droite, l'isthme cingulaire droit et le précuneus droit. Dans l'étude 4 nous avons déterminé le CA du RA chez 30 patients (25 MA et 5 TNC corticaux autres). Le ralentissement du TRS était associé à l'atrophie des cortex préfrontal dorsolatéral droit et SMG gauche. En conclusion, dans les phases précoces de la MA, l'atteinte des FE et le RA faisaient partis du profile cognitif typique. L'atrophie des cortex pariétal inférieur (comprenant le SMG) et à moindre mesure, préfrontal rends compte des dysfonctions exécutives et du RA. Des futures études doivent confirmer ces résultats dans la MA prodromale et précliniqueAlzheimer’s disease (AD) progresses from preclinical isolated subjective cognitive complaints (SCC) to mild neurocognitive disorders (NCD) and then major NCD and is “typically” characterized by prominent memory impairment. In early stages, the intensity of ED and action slowing and their imaging correlates are undetermined. The main objective was to establish in early stages of AD, the intensity of executive dysfunction (ED) and action slowing as well as their imaging correlates. In the Study 1, we showed that executive functions were impaired to a similar extent in AD (with positive CSF biomarkers) and VCI. In the Study 2 we performed a meta-analysis (327 mild NCD and 468 healthy controls) and showed that mean simple reaction time (SRT) was longer in mild NCD group. In the Study 3 we investigated the imaging correlates of ED in MEMENTO cohort (2323 mild NCD or SCC). ED were related to cortical thickness in the left pars orbitalis, right precuneus, right supramarginal (SMG) and the right isthmus cingulate regions. In the Study 4 we determined the imaging correlates (using voxelwise based morphometry) of action slowing in 30 patients with NCD (25 AD, 3 Lewy body dementia, 2 behavioral frontotemporal degeneration). SRT slowing was associated with right dorso-lateral prefrontal and left SMG cortices atrophy. To conclude in early stages of AD, action slowing and ED were a part of the cognitive profile. The atrophy of inferior parietal (including the SMG) and to a lesser extent, of prefrontal cortices accounted for ED and action slowing. In the future studies these results will have to be confirmed in prodromal and preclinical A

COVID-19 encephalopathy: detection of antibodies against SARS-CoV-2 in CSF

International audienc

Imaging Characteristics of Venous Parenchymal Abnormalities

International audienceBackground and Purpose-There are few published data on the patterns of parenchymal imaging abnormalities in a context of cerebral venous thrombosis (CVT). The objectives of the present study were to describe the patterns of parenchymal lesions associated with CVT and to determine the lesion sites. Methods-We included 44 consecutively hospitalized patients with CVT and parenchymal lesions on magnetic resonance imaging. The diagnosis of CVT had been confirmed by magnetic resonance imaging/magnetic resonance venography. Magnetic resonance imaging patterns for CVT were retrospectively analyzed with regard to the lesion's type, shape, and site. Results-The most frequent stroke subtype was hemorrhagic ischemia (in 56.8% of cases), followed by intracerebral hematoma (in 22.72% of cases) and nonhemorrhagic ischemia (in 20.45% of cases). Although there were no significant differences between these 3 groups with regard to the clinical and radiological characteristics, we observed a nonsignificant trend (P=0.08) toward a shorter time interval between hospital admission and magnetic resonance imaging for nonhemorrhagic stroke. The CVT parenchymal abnormalities were centered on 6 main foci and were related to the site of venous occlusion: (1) the inferior parietal lobule (n=20; 44.5%), associated mainly with occlusion of the transverse sinus (n=10) or pure cortical veins (n=10); (2) the inferior and posterior temporal regions (n=10; 22.75%), associated mainly with occlusion of the transverse sinus (n=9); (3) the parasagittal frontal region (n=6; 13.6%), associated mainly with occlusion of the superior sagittal sinus (n=4) or the transverse sinus (n=4); (4) the thalamus (n=5; 11.3%) associated with occlusion of the straight sinus (n=5); (5) the cerebellar hemisphere (n=2; 4.5%), associated in both cases with occlusion of the transverse sinus; and (6) the deep hemispheric regions (n=3; 6.8%), associated with occlusion of the superior sagittal sinus in all cases. Conclusions-Parenchymal lesions caused by CVT display specific anatomic patterns, which is mainly determined by the site of venous occlusion

Imaging Characteristics of Venous Parenchymal Abnormalities

International audienceBackground and Purpose-There are few published data on the patterns of parenchymal imaging abnormalities in a context of cerebral venous thrombosis (CVT). The objectives of the present study were to describe the patterns of parenchymal lesions associated with CVT and to determine the lesion sites. Methods-We included 44 consecutively hospitalized patients with CVT and parenchymal lesions on magnetic resonance imaging. The diagnosis of CVT had been confirmed by magnetic resonance imaging/magnetic resonance venography. Magnetic resonance imaging patterns for CVT were retrospectively analyzed with regard to the lesion's type, shape, and site. Results-The most frequent stroke subtype was hemorrhagic ischemia (in 56.8% of cases), followed by intracerebral hematoma (in 22.72% of cases) and nonhemorrhagic ischemia (in 20.45% of cases). Although there were no significant differences between these 3 groups with regard to the clinical and radiological characteristics, we observed a nonsignificant trend (P=0.08) toward a shorter time interval between hospital admission and magnetic resonance imaging for nonhemorrhagic stroke. The CVT parenchymal abnormalities were centered on 6 main foci and were related to the site of venous occlusion: (1) the inferior parietal lobule (n=20; 44.5%), associated mainly with occlusion of the transverse sinus (n=10) or pure cortical veins (n=10); (2) the inferior and posterior temporal regions (n=10; 22.75%), associated mainly with occlusion of the transverse sinus (n=9); (3) the parasagittal frontal region (n=6; 13.6%), associated mainly with occlusion of the superior sagittal sinus (n=4) or the transverse sinus (n=4); (4) the thalamus (n=5; 11.3%) associated with occlusion of the straight sinus (n=5); (5) the cerebellar hemisphere (n=2; 4.5%), associated in both cases with occlusion of the transverse sinus; and (6) the deep hemispheric regions (n=3; 6.8%), associated with occlusion of the superior sagittal sinus in all cases. Conclusions-Parenchymal lesions caused by CVT display specific anatomic patterns, which is mainly determined by the site of venous occlusion

The cortical lesion pattern of Dysexecutive syndrome in MEMENTO cohort

International audienceObjective: The objective of this study was to investigate the association between cortical thickness and executive functions in the Memento Cohort.Background: Dysexecutive disorders are one early sign of Alzheimer’s disease (AD). Their precise cortical lesion patterns still remain undetermined. Memento cohort is a large French cohort with extensive clinical, neuropsychological and neuroimaging data for studying the natural history of AD in a large group of participants with different subtypes of mild cognitive impairment or isolated subjective cognitive complaints.Design/Methods: We selected from the Memento cohort (Dufouil et al., 2017) all subjects with available region of interest (ROI) cortical thickness data and executive function (verbal fluency and trail making test (TMT)) assessment (n=1924 out of N=2323). Mean MMSE was 28.02 (±1.6), 59.8 % of participants had a Clinical Dementia Rating scale of 0.5, 62.1 % were women. Stepwise linear regression adjusted on age, and education level were achieved to determine reduced brain parenchymal fraction (BPF) and decrease of cortical thickness regions related to both verbal fluency (literal and semantic) and time difference of TMT part B and part A performance (TMTB-At).Results: Semantic fluency was related to BPF and cortical thickness of right supramarginal, right cingulate isthmic and left entorhinal regions (R$^2$=0.133, p=0.0001). Literal fluency was related to BPF and cortical thickness of left pars orbitalis region (R$^2$=0.162, p=0. 0001). TMTB-At was related to cortical thickness of right precuneus and right isthmic cingulate regions (R$^2$=0.142, p=0.0001).Conclusions: The cortical lesion pattern of executive functions was the right supramarginal, right cingulate isthmic, left entorhinal regions, left pars orbitalis and right precuneus. To our knowledge this is the first study to determine precisely, from a large cohort with standardized assessments, the cortical regions related to executive performance

Isolated parkinsonism is an atypical presentation of GRN and C9orf72 gene mutations Authors

International audienceIntroductionA phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their “red flags” according to current IPD criteria.MethodsSeven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and “red flag” features from MDS criteria were analyzed for each case.ResultsAmongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype.ConclusionWe showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations

Glial Fibrillary Acidic Protein Autoimmunity A French Cohort Study

International audienceBackground and Objectives To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies. Methods We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAP alpha since 2017 from 2 French referral centers. Results We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score <= 2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies. Discussion GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome