Benjamin Cretin

Acute limbic encephalitis and glutamic acid decarboxylase antibodies: A reality?

Limbic encephalitis (LE) associated with glutamic acid decarboxylase antibodies (GAD-Ab) is rare. We describe a 30-year-old male with acute LE and GAD-Ab, with follow-up during 2 years of cognitive status including verbal episodic memory, number of seizures recorded by high-resolution video-EEG, brain MRI, 2-[18F]-fluoro-2-deoxyglucose PET and GAD-Ab titres. Treatment with corticosteroids, IV immunoglobulins, immunosuppressors and antiepileptic drugs resulted in improved memory status, disappearance of seizures and decreased GAD-Ab titres. Review of the other cases of literature and this case is in favour of the existence of autoimmune LE associated with GAD-Ab and supports the link between memory, temporal seizures and possibly GAD-Ab titres.

Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages

Objectives To assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimers disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing. Methods Study participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups. Results Comparison of CTh between pro-DLB and pro-AD (p<0.05, FDR corrected) showed more right anterior insula thinning in pro-DLB, and more bilateral parietal lobe and left parahippocampal gyri thinning in pro-AD. Comparison of prodromal patients to healthy elderly controls showed the involvement of the same regions. In DLB-d (p<0.05, FDR corrected) cortical thinning was found predominantly in the right temporo-parietal junction, and insula, cingulate, orbitofrontal and lateral occipital cortices. In AD-d(p<0.05, FDR corrected),the most significant areas affected included the entorhinal cortices, parahippocampal gyri and parietal lobes. The comparison of AD-d and DLB-d demonstrated more CTh in AD-d in the left entorhinal cortex (p<0.05, FDR corrected). Conclusion Cortical thickness is a sensitive measure for characterising patterns of grey matter atrophy in early stages of DLB distinct from AD. Right anterior insula involvement may be a key region at the prodromal stage of DLB and needs further investigation.

Epileptic Prodromal Alzheimer's Disease, a Retrospective Study of 13 New Cases: Expanding the Spectrum of Alzheimer's Disease to an Epileptic Variant?

BACKGROUND Aside from rare case reports, only one study, with 12 patients, has addressed the phenotypic presentation of epilepsy in clinically defined amnestic mild cognitive impairment (aMCI, presumed to correspond to the AD prodromal stage): the authors highlighted a pharmacosensitive non-convulsive partial epileptic syndrome most probably related to the temporal or temporo-frontal cortices. OBJECTIVE The objective of this study was to verify the existence and the syndromic features of epileptic prodromal AD in a tertiary Memory Clinic. METHODS We conducted a retrospective, single-center study of the electro-radio-clinical features of 13 cases of epileptic prodromal AD patients (3.1% of a cohort of MCI, n = 430 subjects), selected on both clinical criteria and CSF biomarkers. RESULTS In our patients, a pharmacosensitive temporal lobe epilepsy syndrome, inaugurating prodromal AD, started at a mean age of 63 years (±12.8 years) and preceded MCI diagnosis by 4 to 7 years. At the stage of aMCI, median MMSE score was 26 and imaging showed mild hippocampal atrophy. After almost one year under treatment, cognitive complaints were not relieved but the MMSE score remained stable at 26 for 11 patients (2 patients were excluded from analysis because of the onset of aphasic or neurovisual symptoms altering MMSE scoring). CONCLUSION Our data, in conjunction with those of the 12 previously described subjects, suggest the existence of a currently unrecognized inaugural epilepsy syndrome of sporadic AD. Such a syndrome could be called the epileptic variant of AD because seizures are its sole feature for more than 2.5 years.

MRI-based volumetry correlates of autobiographical memory in Alzheimer's disease.

The aim of the present volumetric study was to explore the neuro-anatomical correlates of autobiographical memory loss in Alzheimers patients and healthy elderly, in terms of the delay of retention, with a particular interest in the medial temporal lobe structures. Fifteen patients in early stages of the disease and 11 matched control subjects were included in the study. To assess autobiographical memory and the effect of the retention delay, a modified version of the Crovitz test was used according to five periods of life. Autobiographical memory deficits were correlated to local atrophy via structural MRI using Voxel Based Morphometry. We used a ‘lateralized index’ to compare the relative contribution of hippocampal sub-regions (anterior vs posterior, left vs right) according to the different periods of life. Our results confirm the involvement of the hippocampus proper in autobiographical memory retrieval for both recent and very remote encoding periods, with larger aspect for the very remote period on the left side. Contrary to the prominent left-sided involvement for the young adulthood period, the implication of the right hippocampus prevails for the more recent periods and decreases with the remotness of the memories, which might be associated with the visuo-spatial processing of the memories. Finally, we suggest the existence of a rostrocaudal gradient depending on the retention duration, with left anterior aspects specifically related to retrieval deficits of remote memories from the young adulthood period, whereas posterior aspects would result of simultaneous encoding and/or consolidation and retrieval deficit of more recent memories.

Grey matter atrophy in prodromal stage of dementia with Lewy bodies and Alzheimer's disease

BackgroundLittle is known about the patterns of brain atrophy in prodromal dementia with Lewy bodies (pro-DLB).MethodsIn this study, we used SPM8 with diffeomorphic anatomical registration through exponentiated lie algebra to measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB (n = 28) and prodromal Alzheimer’s disease (pro-AD) (n = 27) and compared and contrasted them with those in elderly control subjects (n = 33) (P ≤ 0.05 corrected for family-wise error).ResultsPatients with pro-DLB showed diminished GM volumes of bilateral insulae and right anterior cingulate cortex compared with control subjects. Comparison of GM volume between patients with pro-AD and control subjects showed a more extensive pattern, with volume reductions in temporal (hippocampi and superior and middle gyri), parietal and frontal structures in the former. Direct comparison of prodromal groups suggested that more atrophy was evident in the parietal lobes of patients with pro-AD than patients with pro-DLB. In patients with pro-DLB, we found that visual hallucinations were associated with relative atrophy of the left cuneus.ConclusionsAtrophy in pro-DLB involves the insulae and anterior cingulate cortex, regions rich in von Economo neurons, which we speculate may contribute to the early clinical phenotype of pro-DLB.

Neural correlates of visual hallucinations in dementia with Lewy bodies.

IntroductionThe aim of this study was to investigate the association between visual hallucinations in dementia with Lewy bodies (DLB) and brain perfusion using single-photon emission computed tomography.MethodsWe retrospectively included 66 patients with DLB, 36 of whom were having visual hallucinations (DLB-hallu) and 30 of whom were not (DLB-c). We assessed visual hallucination severity on a 3-point scale of increasing severity: illusions, simple visual hallucinations and complex visual hallucinations. We performed voxel-level comparisons between the two groups and assessed correlations between perfusion and visual hallucinations severity.ResultsWe found a significant decrease in perfusion in the left anterior cingulate cortex, the left orbitofrontal cortex and the left cuneus in the DLB-hallu group compared with the DLB-c group. We also found a significant correlation between decreased bilateral anterior cingulate cortex, left orbitofrontal cortex, right parahippocampal gyrus, right inferior temporal cortex and left cuneus perfusion with the severity of hallucinations.ConclusionsVisual hallucinations seem to be associated with the impairment of anterior and posterior regions (secondary visual areas, orbitofrontal cortex and anterior cingulate cortex) involved in a top-down and bottom-up mechanism, respectively. Furthermore, involvement of the bilateral anterior cingulate cortex and right parahippocampal gyrus seems to lead to more complex hallucinations.

Impaired emotional autobiographical memory associated with right amygdalar-hippocampal atrophy in Alzheimer's disease patients.

We studied the influence of emotions on autobiographical memory (AbM) in patients with Alzheimer’s disease (AD), characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT). Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease.

Cognitive Dysfunction and Dementia in Primary Sjögren’s Syndrome

Background. Primary Sjögrens syndrome (PSS) is a frequent systemic autoimmune disease. In this study, we aimed to explore the cognitive impairment and the correlations with brain MRI. Methods. Twenty-five patients (mean age 55 ± 11.8 years, 21 females) with PSS were prospectively selected and tested with a French translation of the Brief Repeatable Battery for Neuropsychological Examination. The results were compared with the scores for 25 matched patients with multiple sclerosis (MS) and 25 controls. Brain lesions were assessed by brain MRI using the Wahlund classification. Results. Fifteen of the 25 PSS patients (60%) presented with cognitive disorders versus 19/25 MS patients (76%). Five patients had dementia in the PSS group. Speed of information processing, attention, immediate and long-term memory, and executive functions were frequently impaired. The mean duration of cognitive complaints was 5.6 ± 6.1 years, and the mean duration of PSS was 15.8 ± 14.0 years. A trend towards a correlation was found between the severity of cognitive impairment and the degree of white matter lesions (WML) (P = 0.03, rho = 0.43). Conclusion. Cognitive impairment—mild or dementia—exists in patients with PSS. Further MRI studies are needed to better understand the precise neural basis of cognitive impairment in PSS patients.

Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer’s disease

BackgroundTheory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have been published. The aim of our study was to assess ToM in patients with DLB and to search for neural correlates of potential deficits.MethodsThirty-three patients with DLB (DLB group) and 15 patients with Alzheimer’s disease (AD group), all in the early stage of the disease, as well as 16 healthy elderly control subjects (HC group), were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition (FPR) test, the Reading the Mind in the Eyes (RME) test and Ekman’s Facial Emotion Recognition test to assess cognitive and affective components of ToM. Patients underwent cerebral 3-T magnetic resonance imaging, and atrophy of grey matter was analysed using voxel-based morphometry. We performed a one-sample t test to investigate the correlation between each ToM score and grey matter volume and a two-sample t test to compare patients with DLB impaired with those non-impaired for each test.ResultsThe DLB group performed significantly worse than the HC group on the FPR test (P = 0.033) and the RME test (P = 0.015). There was no significant difference between the AD group and the HC group or between the DLB group and the AD group. Some brain regions were associated with ToM impairments. The prefrontal cortex, with the inferior frontal cortex and the orbitofrontal cortex, was the main region, but we also found correlations with the temporoparietal junction, the precuneus, the fusiform gyrus and the insula.ConclusionsThis study is the first one to show early impairments of ToM in DLB. The two cognitive and affective components both appear to be affected in this disease. Among patients with ToM difficulties, we found atrophy in brain regions classically involved in ToM, which reinforces the neuronal network of ToM. Further studies are now needed to better understand the neural basis of such impairment.

Characterization of periodic upper limb movement disorder in a patient with restless arms syndrome.

Restless legs syndrome (RLS) and the frequently associated periodic limb movements (PLM) are common neurological disorders whose pathophysiology remains elusive. We report on the case of a 40‐year‐old patient presenting with severe restlessness in the upper limbs, a poorly known variant of RLS.