A Reliable and Rapid Language Tool for the Diagnosis, Classification, and Follow-Up of Primary Progressive Aphasia Variants

International audienceBackground: Primary progressive aphasias (PPA) have been investigated by clinical, therapeutic, and fundamental research but examiner-consistent language tests for reliable reproducible diagnosis and follow-up are lacking. Methods: We developed and evaluated a rapid language test for PPA ("PARIS") assessing its inter-examiner consistency, its power to detect and classify PPA, and its capacity to identify language decline after a follow-up of 9 months. To explore the reliability and specificity/sensitivity of the test it was applied to PPA patients (N = 36), typical amnesic Alzheimer's disease (AD) patients (N = 24) and healthy controls (N = 35), while comparing it to two rapid examiner-consistent language tests used in stroke-induced aphasia ("LAST", "ART"). Results: The application duration of the "PARIS" was ∼10 min and its inter-rater consistency was of 88%. The three tests distinguished healthy controls from AD and PPA patients but only the "PARIS" reliably separated PPA from AD and allowed for classifying the two most frequent PPA variants: semantic and logopenic PPA. Compared to the "LAST" and "ART," the "PARIS" also had the highest sensitivity for detecting language decline. Conclusions: The "PARIS" is an efficient, rapid, and highly examiner-consistent language test for the diagnosis, classification, and follow-up of frequent PPA variants. It might also be a valuable tool for providing end-points in future therapeutic trials on PPA and other neurodegenerative diseases affecting language processing

Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

The potential of repetitive transcranial magnetic stimulation (rTMS) to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS) to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients

Pathomechanisms Behind Cognitive Disorders Following Ruptured Anterior Communicating Aneurysms: A Diffusion Tensor Imaging Study

International audienceIntroductionAfter the rupture of anterior communicating aneurysms, most patients experience debilitating cognitive disorders; and sometimes even without showing morphological anomaly on MRI examinations. Diffusion Tensor Imaging (DTI) may help understanding the pathomechanisms leading to such disorders in this subset of patients.MethodsAfter independent assessment, we constituted a population of patients with normal morphological imaging (ACOM group). Then, a case-control study comparing volumetric and voxel-based DTI parameters between the ACOM group and a control population was performed. All patients underwent the full imaging and neuropsychological assessments at 6 months after the aneurysm rupture. Results were considered significant when p<2.02.10−4.ResultsTwelve patients were included in the ACOM group: 75% had at least one disabled cognitive domain. Significant differences in DTI parameters of global white matter were noted (average Fractional Anisotropy: 0.915 [±0.05] in ACOM group versus 0.943 (±0.03); p=1.10−5) and in frontal white matter tracts (superior fronto-occipital fasciculus and anterior parts of the corona radiata) as well as in the fornix.ConclusionCognitive disorders are under-estimated, and DTI confirmed that, even when conventional MRI examinations were normal, there were still signs of diffuse neuronal injuries that seemed to dominate in frontal areas, close to the site of rupture

Psychiatric symptoms in anti glutamic acid decarboxylase associated limbic encephalitis in adults: a systematic review

International audienceAutoimmune Limbic Encephalitis (LE) is a relatively new category of immune-mediated diseases with a wide range of neuropsychiatric symptoms. LE associated with Glutamic Acid Decarboxylase (GAD) antibodies is difficult to diagnose due to its possible atypical presentation with neuropsychiatric and behavioral features. We performed a systematic review of literature and retrieved 21 cases of anti GAD-associated LE with neuropsychiatric signs. Median age at onset was 27 years with a female predominance (81.0 %) and median diagnostic delay of 6 months. Clinical presentation included typical LE symptoms such as anterograde amnesia (95.2 %) and temporal lobe or tonico-clonic seizures (95.2 %). Psychiatric symptoms were described in 61.9 % of patients, presenting as anxiety, depressive symptoms, apathy and behavioral changes. Extra-limbic symptoms were present in 14.3 % of patients. No neoplasia associated was found. Some patients had poor epileptic, cognitive and psychiatric outcomes requiring prolonged immunosuppressive treatment. The description of the neuropsychiatric spectrum of anti-GAD LE and its specificities aims to improve our understanding of this entity, and may lead to earlier diagnosis as well as better outcome

Acute Frontal Lobe Dysfunction Following Prefrontal Low-Frequency Repetitive Transcranial Magnetic Stimulation in a Patient with Treatment-Resistant Depression

International audienceThe potential of repetitive transcranial magnetic stimulation (rTMS) to treat numerous neurological and psychiatric disorders has been thoroughly studied for the last two decades. Here, we report for the first time, the case of a 65-year-old woman suffering from treatment-resistant depression who developed an acute frontal lobe syndrome following eight sessions of low-frequency rTMS (LF-rTMS) to the right dorsolateral prefrontal cortex while also treated with sertraline and mianserin. The pathophysiological mechanisms underlying such an unexpected acute frontal lobe dysfunction are discussed in relation to the therapeutic use of LF-rTMS in combination with pharmacotherapy in depressed patients

White matter lesions in FTLD: distinct phenotypes characterize GRN and C9ORF72 mutations

International audienceFrontotemporal lobar degeneration (FTLD) has ahigh frequency of genetic forms; the 2 most commonare GRN (progranulin) and C9ORF72 mutations.Recently, our group reported extensive white matter(WM) lesions in 4 patients with FTLD caused byGRN mutation, in the absence of noteworthy cardiovascularrisk factors,1 in line with other studies inGRN mutation carriers.2,3 Here we compared thecharacteristics of frontal WM lesions in patients withbehavioral variant of FTLD (bv-FTLD) caused byGRN and C9ORF72 mutations

Exploration Deficits Under Ecological Conditions as a Marker of Apathy in Frontotemporal Dementia

International audienceApathy is one of the six clinical criteria for the behavioral variant of frontotemporal dementia (bvFTD), and it is almost universal in this disease. Although its consequences in everyday life are debilitating, its underlying mechanisms are poorly known, its assessment is biased by subjectivity and its care management is very limited. In this context, we have developed “ECOCAPTURE,” a method aimed at providing quantifiable and objective signature(s) of apathy in order to assess it and identify its precise underlying mechanisms. ECOCAPTURE consists of the observation and recording of the patient's behavior when the participant is being submitted to a multiple-phase scenario reproducing a brief real-life situation. It is performed in a functional exploration platform transformed into a fully furnished waiting room equipped with a video and sensor-based data acquisition system. This multimodal method allowed video-based behavior analyses according to predefined behavioral categories (exploration behavior, sustained activities or inactivity) and actigraphy analyses from a 3D accelerometer. The data obtained were also correlated with behavioral/cognitive tests and scales assessing global cognitive efficiency, apathy, cognitive disinhibition, frontal syndrome, depression and anxiety. Here, bvFTD patients (n = 14) were compared to healthy participants (n = 14) during the very first minutes of the scenario, when the participants discovered the room and were encouraged to explore it. We showed that, in the context of facing a new environment, healthy participants first explored it and then engaged in sustained activities. By contrast, bvFTD patients were mostly inactive and eventually explored this new place, but in a more irregular and less efficient mode than normal subjects. This exploration deficit was correlated with apathy, disinhibition and cognitive and behavioral dysexecutive syndromes. These findings led us to discuss the presumed underlying mechanisms responsible for the exploration deficit (an inability to self-initiate actions, to integrate reward valuation and to inhibit involuntary behavior). Altogether, these results pave the way for simple and objective assessment of behavioral changes that represents a critical step for the evaluation of disease progression and efficacy of treatment in bvFTD

Frontal presentation of Alzheimer's disease: A series of patients with biological evidence by CSF biomarkers

ABSTRACT Besides its typical amnesic presentation, focal atypical presentations of Alzheimer's disease (AD) have been described in neuropathological studies. These phenotypical variants of AD (so-called "atypical AD") do not follow the typical amnestic pattern and include non-amnestic focal cortical syndromes, such as posterior cortical atrophy and frontal variant AD. These variants exhibit characteristic histological lesions of Alzheimer pathology at post-mortem exam. By using physiopathological markers, such as cerebrospinal fluid markers, it is now possible to establish in vivo a biological diagnosis of AD in these focal cortical syndromes. We report a series of eight patients who were diagnosed with behavioural variant frontotemporal dementia based on their clinical, neuropsychological and neuroimaging findings, while CSF biomarkers showed an AD biological profile, thus supporting a diagnosis of frontal variant of AD

Cognitive inhibition impairments in presymptomatic C9orf72 carriers

International audiencebjective To investigate cognitive inhibition in presymptomatic C9orf72 mutation carriers (C9+) and its associated neuroanatomical correlates.Methods Thirty-eight presymptomatic C9orf72 mutation carriers (C9+, mean age 38.2±8.0 years) and 22 C9− controls from the PREV-DEMALS cohort were included in this study. They underwent a cognitive inhibition assessment with the Hayling Sentence Completion Test (HSCT; time to completion (part B−part A); error score in part B) as well as a 3D MRI.Results C9+ individuals younger than 40 years had higher error scores (part B) but equivalent HSCT time to completion (part B−part A) compared to C9− individuals. C9+ individuals older than 40 years had both higher error scores and longer time to completion. HSCT time to completion significantly predicted the proximity to estimated clinical conversion from presymptomatic to symptomatic phase in C9+ individuals (based on the average age at onset of affected relatives in the family). Anatomically, we found that HSCT time to completion was associated with the integrity of the cerebellum.Conclusion The HSCT represents a good marker of cognitive inhibition impairments in C9+ and of proximity to clinical conversion. This study also highlights the key role of the cerebellum in cognitive inhibition