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Objectives: To assess the variations and diagnostic performance of serum biomarkers of neurodegenerative diseases., Methods: In this monocentric prospective study, neurofilament light (NFL), T-tau, p-tau181, p-tau217, Aβ40, and Aβ42 were measured in serum collected from orthopedic patients (control group, n=114) and patients in the neurology department (n=69) previously diagnosed with Alzheimer's disease (AD, n=52), parkinsonian syndromes (n=10), and other etiologies of neurodegeneration (non-AD, n=7)., Results: In the control group, serum NFL, T-tau, p-tau181, p-tau217, and Aβ40 significantly increased with age, independently of sex. NFL (p=0.0078), p-tau217 (p<0.001) were significantly increased with neurodegeneration when compared to controls, with only p-tau217 significant in the multivariate analysis (p<0.001). Multivariate regression analysis accounting for age highlighted a significant increase of p-tau217 (p<0.001) in the AD subgroup. NFL was significantly increased in the non-AD patients (p<0.001), and in the parkinsonian syndromes subgroup (p=0.016) when compared to negative controls. Serum p-tau181 and p-tau217 were significantly correlated with CSF p-tau181 (Spearman's coefficients of 0.43 and 0.48 respectively, n=40). Areas under the ROC curves for the identification of patients with neurodegenerative diseases were 0.62 (0.54-0.70) for NFL, 0.62 (0.54-0.71) for T-tau, 0.83 (0.76-0.89) for p-tau217, and 0.66 (0.58-0.74) for Aβ40., Conclusions: Serum biomarkers can help identify patients with neurodegenerative disease and may be a valuable tool for care and orientation. Phosphorylated tau p-tau217 is a promising blood biomarker for AD and NFL for other etiologies., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD)., Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92)., Results: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees., Conclusion: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure., Competing Interests: Conflict of Interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: APP duplication is a rare genetic cause of Alzheimer disease and cerebral amyloid angiopathy (CAA). We aimed to evaluate the phenotypes of APP duplications carriers., Methods: Clinical, radiological, and neuropathological features of 43 APP duplication carriers from 24 French families were retrospectively analyzed, and MRI features and cerebrospinal fluid (CSF) biomarkers were compared to 40 APP-negative CAA controls., Results: Major neurocognitive disorders were found in 90.2% symptomatic APP duplication carriers, with prominent behavioral impairment in 9.7%. Symptomatic intracerebral hemorrhages were reported in 29.2% and seizures in 51.2%. CSF Aβ42 levels were abnormal in 18/19 patients and 14/19 patients fulfilled MRI radiological criteria for CAA, while only 5 displayed no hemorrhagic features. We found no correlation between CAA radiological signs and duplication size. Compared to CAA controls, APP duplication carriers showed less disseminated cortical superficial siderosis (0% vs 37.5%, p = 0.004 adjusted for the delay between symptoms onset and MRI). Deep microbleeds were found in two APP duplication carriers. In addition to neurofibrillary tangles and senile plaques, CAA was diffuse and severe with thickening of leptomeningeal vessels in all 9 autopsies. Lewy bodies were found in substantia nigra, locus coeruleus, and cortical structures of 2/9 patients, and one presented vascular amyloid deposits in basal ganglia., Discussion: Phenotypes associated with APP duplications were heterogeneous with different clinical presentations including dementia, hemorrhage, and seizure and different radiological presentations, even within families. No apparent correlation with duplication size was found. Amyloid burden was severe and widely extended to cerebral vessels as suggested by hemorrhagic features on MRI and neuropathological data, making APP duplication an interesting model of CAA., (© 2023. The Author(s).)

We report the case of a 70-year-old man who developed probable unilateral Creutzfeldt-Jakob disease. Clinically, he presented with right hemiparesis, progressive aphasia, temporospatial disorientation and cerebellar ataxia and later on, myoclonia. The MRI showed a hypersignal from the left caudate in DWI with decreased ADC. Repeated electroencephalograms showed a slow background rhythm in the left hemisphere with superimposed periodic, biphasic and triphasic sharp-wave complexes in the left temporal region. Death occurred after 5weeks. Although exceptional, unilateral Creutzfeldt-Jakob disease was retained as possible., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

We report here the case of a female patient who developed the following behavioural changes after a brain lesion involving the left posterior insula and SII cortices. She discovered de novo artistic capabilities for painting, with an episodic and compulsive need to paint ("hyperpainting"), but also exhibited changes in her ability to feel emotions. In addition, she had a typical neuropathic pain syndrome, including provoked pain and spontaneous pain, whose intensity was worsened when she painted with cold colours. This case-report suggests some kind of synaesthesiae, which has previously been reported for other sensory modalities. These findings suggest that a cross-talk between emotional, thermosensory, pain, and motivational functions may take place during recovery, at the level of the left insular-SII cortices., (Copyright 2010. Published by Elsevier B.V.)

Introduction: Tracking can be proposed for subjects with prodromal sates of Alzheimer disease (AD) or people with mild cognitive impairment (MCI) at risk to develop dementia who present a memory complaint., Patients and Methods: We present a cohort of 100 subjects who attended a French memory unit with a diagnostic of MCI. We applied the different definitions used in daily practice. We used the following diagnostic criteria: amnestic MCI (MCIa), multiple domain impairment (MDI), single non-memory dysfunction impairment (SDI), and prodromal Alzheimer's disease (Prod-AD), using only the neuropsychological episodic memory criteria. We also analyzed the population of subjects presenting MCI and vascular risk factors., Results: Ninety-nine subjects met the criteria of MCIa, 43 met the criteria of isolated MCIa; 56 met the criteria of MDI; one met the criteria of SDI; 40 met the criteria of MAPD; 58 met the criteria of MCI with vascular risk factors., Discussion: Using the diagnostic criteria of MCI can lead to clinical ambiguity because the population recruited on the bases of memory complaint is highly variable. Moreover, many subjects meet many definitions. This overlap of the classifications further complicates the decision to favor one criterion over another. In clinical practice, a classification system using the concepts of MCI, MDI and SDI seems to be quite operational but cut-offs are necessary for the tests applied, in addition to a clarified choice of which tests to use.

Introduction: Meningoencephalitis is the most common central nervous system complication caused by Mycoplasma pneumoniae. Its frequency is probably underestimated., Objective: The study's aim was to determine the retrospectively incidence of M. pneumoniae meningoencephalitis among other cases of encephalitis diagnosed in infectiology, neurology and ICU at the Clermont-Ferrand University hospital in 2004 and 2005., Design: A case of meningoencephalitis was defined by encephalopathy (altered level of consciousness and/or change in personality), with one or more of the following symptoms: fever, seizure, focal neurological findings, meningitis, electroencephalography or neuroimaging findings consistent with encephalitis. Tumor and hematoma diagnosed by scan were excluded. M. pneumoniae was considered as a possible cause when patients had positive serological test (IgM Elisa) and/or positive PCR results for the CSF., Results: Four (8.3%) patients among 48 cases of encephalitis could have been caused by M. pneumoniae. All except one convulsed initially. Pneumopathy was found in two patients. All received a specific treatment later. Antibiotics seemed to influence evolution in only two patients. These 4 cases appeared during an epidemic between November 2004 and August 2005: 48 hospitalized adults had positive serological test for M. pneumoniae in 2005 and 15 in 2004, whereas the number of tests was the same in 2004 and in 2005., Conclusions: M. pneumoniae should be investigated as a cause of meningoencephalitis if initial tests are negative, if patients have respiratory symptoms and in case of epidemic. Presumptive treatment of meningoencephalitis should include an antibiotic active against M. pneumoniae.

Introduction: Between 4 and 15% of solid cancers are associated with carcinomatous meningitis ant its unfavorable prognosis. The clinical presentation of neoplastic meningitis typically associates cerebral signs, cranial nerve involvement, and medullary or radicular symptoms., Observation: We report a case of a 58-year-old woman, with a history of breast cancer in remission since 8 years, who presented an acute paraparesia and a pure motor deficit of the left arm. This diffuse lower motor neuron disease was the inaugural sign of carcinomatous meningitis., Conclusion: The diagnosis of cacinomatous meningitis is based on medullar MRI and lumbar puncture. In same cases, clinical signs are limited to a pure diffuse lower motor neuron disease.