Introduction Les troubles olfactifs (ou dysosmies) ont gagné en visibilité lors de la pandémie du COVID-19. Ils sont également reconnus comme des symptômes prodromaux de la maladie de Parkinson idiopathique (MPI). Objectifs Cette étude a pour objectif de comparer les profils olfactifs subjectifs et objectifs chez des patients avec MPI et en post-COVID-19 afin d’identifier des marqueurs discriminants entre ces deux groupes. Méthodes Deux groupes appariés (20 MPI<3 ans d’évolution, 20 post-COVID avec dysosmies) ont été recrutés en neurologie et ORL. Tous ont réalisé le Sniffin’ Sticks test (seuil, discrimination, identification, score total) et été classés comme normaux, borderline ou pathologiques. Les données sociodémographiques, une EVA olfactive et l’échelle HAD ont été recueillies. Les patients MPI ont aussi complété l’échelle d’apathie de Starkstein, le questionnaire TCSP et le score moteur UPDRS-III. Résultats Les patients avec MPI présentaient une discrimination (1,6±0,36 vs 0,8±0,36, p=0,009) et un score total (1,7±0,36 vs 0,9±0,36, p=0,014) plus altérés, tandis que les patients post-COVID-19 rapportaient davantage de plaintes subjectives et de troubles qualitatifs (parosmie, phantosmie). L’association de l’EVA avec la discrimination ou le score total permettait de distinguer de manière fiable les deux groupes. Chez les patients MPI, la performance olfactive était corrélée à l’âge (r=−0,77, p<0,001), à la durée de la maladie (r=0,46, p=0,041), au score UPDRS-III (r=0,71, p<0,001), aux TCSP (r=0,53, p=0,017), à l’anxiété (r=0,51, p=0,020) et à l’apathie (p=0,0109) Discussion Les profils olfactifs diffèrent nettement : neurodégénérescence dans la MPI versus atteinte mucosale régénérative post-COVID. Dans la MPI, les liens entre olfaction et paramètres cliniques confirment sa valeur de marqueur évolutif. À l’inverse, parosmies/phantosmies et concordance subjective-objective post-COVID évoquent une reconstruction olfactive. L’imagerie TEP-FDG (littérature) montre une atteinte diffuse dans la MPI et surtout fronto-limbique après COVID. Conclusion Les patients MPI et post-COVID présentent des profils olfactifs distincts. Intégrer la rééducation olfactive en orthophonie pourrait améliorer les fonctions cognitives et comportementales des patients MPI.

Background Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor fluctuations (MF) in Parkinson’s disease (PD), but its impact on non-motor fluctuations (NMF) remains unclear. As NMFs are frequent, disabling, and affect quality of life, understanding their response to DBS is critical. Objectives To assess the presence of NMF after STN-DBS, identify preoperative factors of improvement, and compare NMF responses to DBS and levodopa. Methods This project is an ancillary study of the French multicenter PREDISTIM cohort. We used the validated Non-Motor Fluctuation Severity Scale (NMF2S) to evaluate NMFs one year after STN-DBS and before surgery when data were available. Evaluations were performed under standardized conditions (OFF-Dopa/OFF-Stim vs. OFF-Dopa/ON-Stim). Results We included 284 PD patients assessed one year after STN-DBS using the NMF2S scale. Preoperative data were available for 153 patients. Evaluations were performed under standardized stimulation conditions (OFF-Dopa/OFF-Stim vs. OFF-Dopa/ON-Stim).STN-DBS led to a 41.1% reduction in NMF severity, with anxiety, concentration difficulties, and pain showing the most improvement. However, DBS effects were less pronounced than those of levodopa, especially for psychiatric symptoms. NMF improvement did not correlate with motor improvement. Among all preoperative variables, only the levodopa response in the cognitive domain was associated with post-DBS NMF benefit. Conclusions STN-DBS significantly improves NMFs, although to a lesser extent than levodopa. The dissociation between motor and non-motor responses underscores the need for specific markers to predict NMF outcomes. These findings support the integration of NMF assessment into DBS indications and patient selection.

Evidence in Alzheimer’s disease and other dementias shows that changes in cerebrospinal fluid (CSF) turnover and perivascular spaces (PVS) volume are associated with disease progression through impairment of waste-clearance glymphatic pathways. Volume of CSF, PVS, and drainage structures such as venous sinus are mostly excluded in current MRI studies of premanifest synucleinopathy. Here, we used 7 Tesla MRI to investigate whether modifications in CSF, PVS, and venous sinus volumes occur in 18 prodromal synucleinopathy patients (namely isolated rapid-eye-movement sleep behavior disorder, iRBD) compared to 20 healthy young and 18 elderly controls. Our results demonstrated increased CSF and PVS volumes in iRBD without a matching increase in drainage venous structures, as observed in elderly controls. This suggests increased CSF and PVS fluid stasis, possibly due to impaired CSF filtration, a mechanism that could reduce glymphatic function and exacerbate the neurodegenerative process in iRBD.

La constatation d’une atrophie cortico-sous-corticale jugée « marquée pour l’âge » à l’imagerie par résonance magnétique (IRM) est une situation fréquente en pratique neurologique. Longtemps considérée comme un marqueur quasi équivalent de neurodégénérescence, elle ne saurait aujourd’hui constituer à elle seule un diagnostic. Le recours à l’IRM multimodale avec notamment les séquences FLAIR, diffusion, de susceptibilité magnétique et ASL permet d’écarter des diagnostics différentiels et de rechercher des arguments supplémentaires en faveur d’un diagnostic donné. Également, l’émergence de nouvelles approches en imagerie (comme l’évaluation de l’eau « libre », du système glymphatique) ainsi que des biomarqueurs biologiques ou issus de dispositifs portables, oblige à reconsidérer la place de l’atrophie isolée dans l’arsenal diagnostique. Aujourd’hui, l’atrophie doit être intégrée, combinant clinique, imagerie et autres biomarqueurs. Cet article propose une lecture critique de la valeur de l’atrophie cérébrale à l’IRM, insiste sur les pièges interprétatifs, et discute les apports récents ayant un impact direct sur la pratique clinique.

Background Functional neurological disorders (FND) represent a significant public health challenge due to their prevalence and impact on quality of life. Functional movement disorders (FMD) and functional gait disorders (FGD) represent a large part of the broad phenotype spectrum of FND. Objective This study aimed to describe the clinical profiles and associated characteristics of FMD and FGD, with particular attention to age-related symptoms. Methods A retrospective review of medical records with standardized collection of data of FND and FMD patients from three Neurological Referral Centers was conducted from 2016 to 2024. Data collected included demographic information and clinical outcomes. Results Sixty-eight patients were included with a female predominance (75.53 %). Thirty-seven had FMD (mean age 47.19 ± 18.66 years), 14 had FGD (63.0 ± 11.50), and 17 had both (49.53 ± 20.90 years). FGD were more frequent in older patients compared with FMD patients (p = 0.0046) and with patients with the mixed phenotype (p = 0.043). Tremors were the most common FMD subtype (70.3 %), while astasia-abasia was the predominant FGD phenotype (57.1 %). Fifty-three percent of patients were lost to follow-up, 20.6 % improved, and 26.5 % remained stable. Lack of physical and psychological rehabilitation was predominant in lost-to-follow-up subjects. Conclusion FND age of onset was significantly associated with phenotype, with older patients being more affected by FGD. This association may be partially influenced by societal perceptions of aging and mobility.

Huntington's disease (HD) is characterized by a combination of motor, cognitive, and neuropsychiatric impairments. Among them, impulsivity and attention deficits are clinical features usually described in HD, impacting the quality of life of patients and their caregivers. Twenty early-stage HD patients (PHD) and 20 age and gender-matched control participants (CP) performed a "Simon" reaction time (RT) task allowing us to explore action impulsivity and attention deficits. Surface EMG recordings aimed at revealing the presence and characterizing the nature of impulsivity in PHD. Correlational analyses between error rates or chronometric data, and clinical or neuropsychological data were examined. (1) Analysis of the accuracy and EMG patterns revealed no difference between PHD and CP, indicating absence of motor impulsivity at the early stage of HD. (2) Chronometric indices revealed a general slowing of information processing in PHD, involving central information processing but sparing the latest stages of motor execution, consistent with performed correlational analysis. (3) Sequential analysis of RT patterns showed a failure to allocate attention appropriately. These indices of attentional deficits nicely correlated with performance in neuropsychological tests exploring attentional processes. (1) Central information processing slows down at the early stage of HD but the latest steps of motor execution are unaffected. (2) In the progression of HD, attentional deficits typically should appear first among dysexecutive problems, without significant action impulsivity.

BACKGROUND: The pathophysiology of normal pressure hydrocephalus (NPH) has not been fully elucidated. Treating NPH with cerebrospinal fluid shunts to improve gait disturbances may have some risks and inconsistent benefits. No clear predictive factor has been identified thus far. This preliminary study aimed to evaluate the predictive value of preoperative brain 18F-FDG positron emission tomography (PET) on overall gait response in patients with NPH. METHODS: Sixteen patients with NPH who underwent 18F-FDG PET before shunt surgery between 2012 and 2022 were included retrospectively and separated into two groups based on their gait response one year after surgery: responders (R) or nonresponders (NR). Brain glucose metabolism was assessed using visual and semiquantitative analyses using SPM8 software (Welcome Department of Cognitive Neurology, University College, London, UK). Five regions of interest were selected: global cortex, cerebellum, thalamus, striatum, and midbrain. RESULTS: Visual interpretation showed more frequent hypometabolism of the striatum, thalamus and global cortex in NR. None of the patients showing hypometabolism of these regions were R. Based on these results, the visual interpretation allowed us to identify 3/8 NR and 8/8 R. Semiquantitative analysis confirmed significantly lower thalamic metabolism in the NR group (P=0.037) and a trend towards lower metabolism of the striatum (P=0.075) with an area under the curve of 0.77 for thalamic metabolism to discriminate between R and NR. CONCLUSIONS: This preliminary study using brain 18F-FDG PET suggests that reduced brain metabolism in the thalamus and striatum along with cortical hypometabolism may be associated with poorer gait response to CSF shunting in normal pressure hydrocephalus (NPH). Although these findings suggest that preoperative brain 18F-FDG PET could potentially aid in selecting appropriate candidates for shunt surgery, further research with larger sample sizes is needed to confirm these results. improvement after cerebrospinal fluid shunting in normal pressure hydrocephalus? Q J Nucl Med Mol Imaging 2024;68:179-86. DOI: 10.23736/

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. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Phenotypes of CANVAS are increasingly diversified, including bradykinesia and dysautonomia, so that its primary differential diagnoses are multiple system atrophy-cerebellar type (MSA-c), and spinocerebellar ataxia type 3 (SCA3). This case series aims to highlight key molecular imaging findings in CANVAS. CASES:We report a case series of six patients with CANVAS who underwent nuclear medicine examinations in our center and 13 patients from the literature. These include 18F-FDG brain positron emission tomography (PET), single photon emission computed tomography (SPECT) of dopamine transporter (DaT) activity, and 123I-MIBG cardiac scintigraphy of noradrenergic transmission. CONCLUSIONS:In CANVAS, 18F-FDG brain PET mainly shows cerebellar hypometabolism, with preserved brainstem and striatum metabolism, contrasting with SCA3 and MSA-c. Dopaminergic denervation on scintigraphy seems to be associated with clinical parkinsonism, ranging from normal to severely impaired DaT SPECT. Additionally, 123I-MIBG cardiac scintigraphy might show denervation in CANVAS, similar to SCA3, but not in most MSA-c patients.

Introduction: Identifying biomarkers reflecting cellular dysfunctions in early Parkinson's disease patients (ePD) is needed to develop targeted therapeutic strategies. We aimed to determine if cellular energetic dysfunction related to increased brain sodium concentration would be co-located to microstructural alterations and iron deposition in ePD. Methods: We prospectively included 12 ePD (mean disease duration 20.0 +/- 10.2 months) and 13 healthy controls (HC), scanned with a 7 T H-1 and Na-23 MRI. Complementary voxel-based and region-based assessments were performed, the latter utilizing a high-resolution multimodal template we created (combining quantitative T1 maps (qT1), transverse relaxation rate (R-2*), quantitative magnetic susceptibility mapping (QSM) images) from 200 subjects. This template allowed a precise multiparametric assessment of sodium concentration, QSM, R-2*, qT(1), mean diffusivity, and fractional anisotropy values. A two-sided p-value<0.05 was considered statistically significant after the Bonferroni correction. Results: Relative to HC, ePD showed significantly higher sodium concentration in left Substantia nigra (SN) pars reticulata (46.13 mM +/- 3.52 vs 38.60 mM +/- 6.10, p = 0.038), a subpart of the SN pars compacta (SNc) and ventral tegmental area, Putamen, Globus Pallidum external, accumbens nucleus and claustrum. Significantly increased QSM and R2* values, and decreased T-1 values, were limited to the Nigrosomes 1 (Nig) and right SNc (all p < 0.05). QSM values in the Nig were significantly correlated to UPDRS-III scores (r = 0.91,p < 0.001). Conclusion: In ePD, brain sodium accumulation was broad and dissociated from iron accumulation. As with iron accumulation, a sodium-related pathophysiological approach could lead to identifying potential new therapeutic agents and deserves further investigation.

A 72-year-old man with rapidly progressive gait disturbances and behavioral changes was referred to our Movement Disorders unit. His brain magnetic resonance images (Fig. 1) showed the face of the giant panda sign, which is considered characteristic of Wilson's disease (WD).1 Although late-onset WD cases are possible, his age and periventricular gadolinium-enhanced lesions prompted us to consider other diagnostic possibilities. Cerebrospinal fluid examination revealed no intrathecal immunoglobulin synthesis, normal protein levels, and red and white cell counts. A brain biopsy was performed and revealed a diffuse B-cell primary central nervous system lymphoma. Brain magnetic resonance images. Multiple-choice question with Figure 1: A.The red arrow refers to the eyes of the tiger sign. B.The red arrow refers to the face of the giant panda sign. C.This sign is usually seen in Wilson's disease. D.Here, alternative diagnoses should be ruled out. Correct answers: B, C, D. Explanation in the text. The face of the giant panda sign (red arrows) is discernible on FLAIR (fluid-attenuated inversion recovery) and T2-weighted axial midbrain slice images: high signal intensity of the tegmentum with normal hypointense red nuclei and preserved signal intensity of the substantia nigra pars reticulata. Periventricular gadolinium-enhanced lesions are indicative of an alternative diagnosis. Other rare conditions such as Japanese B encephalitis (with bilateral hemorrhagic lesions in the thalami), Leigh's disease, methanol poisoning (with bilateral putaminal hemorrhagic necrosis), hypoxic-ischemic encephalopathy, extrapontine myelinolysis, cysticercal granuloma of the midbrain (with ring-enhancing gadolinium lesion),2 Maple syrup urine disease, glucaric aciduria type 1, non-Wilsonian hepatolenticular degeneration (intense T1 shortening contrasts with the usual T1 hypointensities in WD), isoniazid-induced ataxia and metronidazole neurotoxicity (red nucleus hyperintensities as "bright eyes" of the panda) may produce a face of the giant panda sign (supplemental references in Data S1). In conclusion, the age of onset over 40 years, atypical, or gadolinium-enhanced brain lesions in a case with the face of the giant panda sign should lead to further investigation to focus on treatable conditions. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical analysis: A. Design, B. Execution, C. Review and critique; (3) Manuscript preparation: A. Writing of the first draft, B. Review and critique. M.P.: 1A, 1B, 1C, 3A L.S.: 1A, 1B, 3B S.G.: 1A, 1B, 1C, 3B Ethical Compliance Statement: Verbal and written informed consent were obtained from the subject. He was offered the opportunity to read this article and review the images but waived his right to do so. The authors confirm that the approval of an institutional review board was not required for this work. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflicts of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report. Data sharing not applicable. Data S1. Supplemental references. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The increasing number of MRI studies focused on prodromal Parkinson's Disease (PD) demonstrates a strong interest in identifying early biomarkers capable of monitoring neurodegeneration. In this systematic review, we present the latest information regarding the most promising MRI markers of neurodegeneration in relation to the most specific prodromal symptoms of PD, namely isolated rapid eye movement (REM) sleep behavior disorder (iRBD). We reviewed structural, diffusion, functional, iron-sensitive, neuro-melanin-sensitive MRI, and proton magnetic resonance spectroscopy studies conducted between 2000 and 2023, which yielded a total of 77 relevant papers. Among these markers, iron and neuromelanin emerged as the most robust and promising indicators for early neurodegenerative processes in iRBD. Atrophy was observed in several regions, including the frontal and temporal cortices, limbic cortices, and basal ganglia, suggesting that neurodegenerative processes had been underway for some time. Diffusion and functional MRI produced heterogeneous yet intriguing results. Additionally, reduced glymphatic clearance function was reported. Technological advancements, such as the development of ultra-high field MRI, have enabled the exploration of minute anatomical structures and the detection of previously undetectable anomalies. The race to achieve early detection of neurodegeneration is well underway.

Background New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. Objectives To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Methods Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Results Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. Conclusions These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.