[Dementia: Where are the Lewy bodies?]. / Démences : où sont les corps de Lewy ?

Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in autopsy studies. In clinical pratice however, the prevalence of DLB is much lower with important intercenter variations. Among the reasons for this low sensitivity of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of Lewy bodies with Alzheimer's disease pathology, which dominates the clinical phenotype. With the avenue of targeted therapies against the protein agregates, new clinical scales able to apprehend the coexistence of Lewy pathology in Alzheimer's disease are expected.

Zero the hero: Evidence for involvement of the ventromedial prefrontal cortex in affective bias for free items.

Recent evidence from psycho-economics shows that when the price of an item decreases to the extent that it becomes available for free, one can observe a remarkable increase of subjective utility toward this item. This phenomenon, which is not observed for any other price but zero, has been termed the zero-price effect (ZPE). The ZPE is attributed to an affective heuristic where the positive affect elicited by the free status of an item provides a mental shortcut biasing choice towards that item. Given that the ZPE relies on affective processing, a key role of the ventromedial prefrontal cortex (vmPFC) has been proposed, yet neuroscientific studies of the ZPE remain scarce. This study aimed to explore the role of the vmPFC in the ZPE using a novel, within-subject assessment in participants with either an acquired (lesion patients) or degenerative (behavioural-variant frontotemporal dementia patients) lesion of the vmPFC, and age-matched healthy controls. All participants were asked to make a series of choices between pairs of items that varied in price. One choice trial involved an equal decrease of both item prices, such that one of the items was priced zero. In contrast to controls, patients with both vmPFC-lesion and behavioural-variant frontotemporal dementia showed marked reductions in zero-related changes of preference in pairs of gift-cards, but not for pairs of food items. Our findings suggest that affective evaluations driving the ZPE are altered in patients with focal or degenerative damage to the vmPFC. This supports the notion of a key role of the vmPFC in the ZPE and, more generally, the importance of this region in value-based affective decision-making. Our findings also highlight the potential utility of affective heuristic tasks in future clinical assessments.

A case of transthyretin-related cerebral amyloid angiopathy. The other side of hereditary transthyretin amyloidosis.

The target organs for familial transthyretin amyloidosis are typically the nerves, the heart or even the eyes due to the accumulation of amyloid deposits. Less frequently, these deposits can occur within the central nervous system and drive a specific phenotype of cerebral amyloid angiopathy. We report the case of a 72-year-old woman showing evidence of cerebral amyloid angiopathy, in a context of hereditary transthyretin amyloidosis (hATTR) due to p.(Ser77Tyr) mutation of the TTR gene. Her cognitive assessment on a two-year follow-up was remarkably steady. A very limited number of patients with hereditary transthyretin amyloidosis associated with a cerebral amyloid angiopathy have been reported. Few characteristics could distinguish them from classic cerebral amyloid angiopathy, and more data are needed to highlight specific features. Screening for peripheral neuropathy should be considered for patients referred to memory clinic for atypical cerebral amyloid angiopathy.

Emotional facial palsy following striato-capsular infarction.

Emotional facial palsy (EFP) is a rare condition in which facial paresis is only apparent during reflex movements of the hemiface, such as smiling and laughter. We report the case of a 32-year-old man presenting with EFP as the main symptom of a small striatocapsular infarction. Our case strongly suggests that the anterior arm of the internal capsule is part of the corticonuclear tract that is involved in emotional facial motility.

[Acute anterograde amnesia by infarction of the mamillothalamic tracts]. / Syndrome amnésique aigu par infarctus des faisceaux mamillothalamiques de Vicq d'Azir.

We report a case of persistent anterograde amnesia secondary to an anterior thalamic infarct. A 49-year-old right-handed man is referred for acute anterograde amnesia. Diffusion-weighted imaging performed at 24 hours shows an acute punctiform infarct of the left anterior thalamus, while T2-weighted imaging reveals a contralateral and symmetrical ischemic sequelae in the right anterior thalamus. The two lesions are isolated and remarkably centered with the mamillothalamic tract. We suggest the symptoms are caused by the addition of the two lesions interrupting the mamillothalamic tracts. This is the second clinico-pathological observation of a persistent amnestic syndrome secondary to a bilateral lesion of the mamillothalamic tract.

Leptomeningeal carcinomatosis from ethmoid sinus adenocarcinoma.

INTRODUCTION: Adenocarcinoma of the ethmoid is an aggressive tumor, with potential extension to surrounding structures. Leptomeningeal extension is a rarely reported entity. CASE REPORT: A carpenter, aged 55, developed multifocal cranial nerve-related symptoms 1 week after resection of adenocarcinoma of the ethmoid, evolving towards deteriorated general health status and death 10 weeks later. Brain MRI showed diffuse contrast enhancement of the cranial nerves, and repeated cerebrospinal fluid (CSF) examination found increased protein concentration associated with decreased glucose concentration, without malignant cells. The diagnosis of carcinomatous meningitis was based on the association of clinical, CSF and brain MRI data. DISCUSSION/CONCLUSION: Leptomeningeal dissemination of adenocarcinoma of the ethmoid is rare; diagnosis is guided by clinical signs. MRI reveals neurological spread, but the presence of malignant cells in the CSF is sufficient for diagnosis. Due to poor prognosis, the only currently available treatments are palliative.

A comparison between colonic submucosa and mucosa to detect Lewy pathology in Parkinson's disease.

BACKGROUND: Lewy bodies and neurites (LN), the two pathological hallmarks of Parkinson's disease (PD), are found in the enteric nervous system (ENS). Previously, we have shown that whole mounts of submucosa obtained after microdissection of colonic biopsies can be used for the detection of LN in the submucosal plexus (SMP) of PD patients. Recent reports suggest that Lewy pathology may extend beyond the submucosa to involve the digestive mucosa. The aim of the present research was to determine whether the analysis of the mucosa obtained after microdissection may help improve the sensitivity of colonic biopsies to detect Lewy pathology in the colon of PD patients. METHODS: Nine PD patients and 10 controls were included. Four biopsies were taken from the sigmoid/descending colon junction during the course of a rectosigmoidoscopy (short colonoscopy) in PD patients and during a total colonoscopy for colorectal screening in controls. Biopsies were microdissected, the mucosa was separated from the submucosa and both structures were analyzed by immunohistochemistry. Immunohistochemical analysis was performed using antibodies against phosphorylated alpha-synuclein to detect LN and neurofilaments NF200 kDa to label the neuronal structures. KEY RESULTS: Lewy neurites were present in the SMP of four patients and in the mucosa of three patients. Remarkably, among the patients who displayed LN within their mucosa, one was devoid of Lewy pathology in his SMP. No LN were observed in the mucosa and the SMP of controls. CONCLUSIONS & INFERENCES: The parallel analysis of colonic mucosa, along with the SMP, can help detect Lewy pathology in PD.

[Enteric nervous system and Parkinson's disease]. / Système nerveux entérique et maladie de Parkinson.

It has become increasingly evident over the last years that Parkinson's disease is a multicentric neurodegenerative disease that affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. The aims of the present article are to discuss the role of the enteric nervous system lesions in pathology spreading (Braak's hypothesis) and in the gastrointestinal dysfunction encountered in Parkinson's disease. Owing to its accessibility to biopsies, we further discuss the use of the enteric nervous system as an original source of biomarker in Parkinson's disease.

Parkinson disease: the enteric nervous system spills its guts.

Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as "the brain in the gut" because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders.

Routine colonic biopsies as a new tool to study the enteric nervous system in living patients.

Better characterization of enteric neuropathies during the course of gastrointestinal diseases could be of great diagnostic and/or therapeutic interest. However, studies using whole mounts of the enteric nervous system (ENS) are restricted to specific diseases requiring surgery and are also limited by the small number of specimens available. Therefore, we here describe a novel method to obtain whole mounts of submucosal plexus in routine colonic biopsies. We show that a single biopsy displays a substantial number of submucosal ganglia and neurons and that it can be reliably used to perform morphometric and neurochemical analysis and Western Blots quantification of neuronal or glial markers. This method of analysis of the human ENS will enable us to gain better insight into the characterization of enteric neuropathies in living patients.

Neurochemical plasticity in the enteric nervous system of a primate animal model of experimental Parkinsonism.

Emerging evidences suggest that the enteric nervous system (ENS) is affected by the degenerative process in Parkinson's disease (PD). In addition lesions in the ENS could be associated with gastrointestinal (GI) dysfunctions, in particular constipation, observed in PD. However, the precise alterations of the ENS and especially the changes in the neurochemical phenotype remain largely unknown both in PD and experimental Parkinsonism. The aim of our study was thus to characterize the neurochemical coding of the ENS in the colon of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, a well-characterized model of PD. In the myenteric plexus, there was a significant increase in the number of neurons per ganglia (identified with Hu), especially nitric oxide synthase immunoreactives (IR) neurons in MPTP-treated monkeys compared to controls. A concomitant 72% decrease in the number of tyrosine hydroxylase-IR neurons was observed in MPTP-treated monkeys compared to controls. In contrast no change in the cholinergic or vasoactive intestinal peptide-IR population was observed. In addition, the density of enteric glial cells was not modified in MPTP-treated monkeys. Our results demonstrate that MPTP induces major changes in the myenteric plexus and to a lesser extent in the submucosal plexus of monkeys. They further reinforce the observation that lesions of the ENS occur in the course of PD that might be related to the GI dysfunction observed in this pathology.