Revue neurologique最新文献

Background: Parkinson's disease (PD) patients often report seeing persons or animals rather than objects but this phenomenon remains poorly understood. Here, we use three experimental tasks to confirm such observation and to explore its cognitive mechanisms.

Method: Fourteen PD patients with visual hallucinations (PD-VH), 14 PD patients without visual hallucinations (PD-NVH) and 14 controls with similar cognitive performance were tested using ambiguous stimuli. Ambiguous stimuli were morphs in which visual features from faces and flowers were melted together (Experiments 1 and 2) and a black and white picture where a Dalmatian dog was hidden (Experiment 3). In Experiment 1, participants categorised ambiguous stimuli either as face or flower. In Experiment 2, they were shown an ambiguous stimulus, then a mask, and finally two ambiguous stimuli, one of which was identical to the first stimulus. In this discrimination task, participants chose which of the two last stimuli had been presented before. In Experiment 3, participants guessed the items hidden in the picture. We assessed group differences for categorisation with logistic modelling and computed sensitivity index and criterion psychophysical measures in Experiments 1 and 2. The ratio of living beings identified in the Dalmatian dog task was compared across groups.

Results: In the categorisation task, the PD-VH group tended to use a smaller proportion of visual features (point of subjective equality [PSE]=41.5%) to label a stimulus as Face compared to PD-NVH (51%) and controls (56.2%). In the discrimination task, criterion c was lower in the PD-VH group compared to controls (c: -0.16 vs. 0.27; P=0.005). In the Dalmatian dog task, the PD-VH group reported seeing livings beings more frequently than controls (P=0.040). A bias towards living beings was confirmed in the PD-VH group in the three tasks, and a bias toward non-living beings was measured in controls in the discrimination task.

Interpretation: Observing that controls exhibited bias toward non-living beings in the discrimination task, we suggest that impaired top-down control over perception processes explains the bias toward living beings in PD-VH visual misperceptions.

Introduction: Myotonic dystrophy type 1 (DM1) is a genetic multisystemic disorder, affecting the muscles but also the brain and other organs, and impacting quality of life (QoL). Most of previous studies focused on health-related QoL and its predictors, which might restrict the possibility to observe the consequences of more general factors on QoL.

Methods: We studied QoL from a more global point of view in adult non-congenital DM1 patients included in the DM-VASCOG cohort using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire, which discriminates four domains (physical health, psychological state, social relationships, and environment). Social participation was also evaluated using a questionnaire designed to assess the frequency of and the degree of satisfaction with the patient's involvement in social activities. Associations of these questionnaires with demographic, DM1-related, neuropsychological and behavioral measures were analyzed.

Results: Among our 122 DM1 patients, lower scores for the physical QoL were observed compared to other dimensions (P<0.001). QoL predictors were different among the physical (motor function, fatigue), psychological (anxiety, depression), social (education, depression) and environmental (anxiety, depression, fatigue) dimensions. Frequency of social participation in DM1 patients was associated with executive functions (Stroop test), while satisfaction with social participation was associated with depression and fatigue.

Conclusion: The different dimensions of QoL and social participation in adult DM1 are associated with different modifiable factors. The effect on QoL of interventions focusing on these factors should be studied in future DM1 trials.

Gerstmann-Sträussler-Scheinker syndrome is an extremely rare hereditary human prion disease caused by distinct mutations in the prion protein-encoding gene and is frequently associated with a positive family history. The disease typically presents with progressive cerebellar symptoms such as gaze apraxia with limb ataxia and axial ataxia; thus, the diagnostic process is often challenging due to nonspecific clinical presentation. We present a case of a 73-year-old patient with no family history of dementia and cerebellar symptomatology during the course of rapidly progressing dementia. Owing to the clinical suspicion of prion disease, antemortem analysis of cerebrospinal fluid using a real-time quaking-induced conversion (RT-QuIC) assay was performed, with positive results. Postmortem histopathological examination confirmed a familiar form of human prion disease with concomitant asymptomatic tauopathy. An additional finding was a novel 6 octapeptide repeat insertion mutation in the prion gene. Familiar cases with an increasing number of repeated insertions seem to be associated with a longer overall disease course, milder clinical deterioration and often false-negative RT-QuIC results. The performance of RT-QuIC in inherited prion diseases may vary. Our case, involving a 6 octapeptide repeat insertion mutation, is particularly noteworthy due to the rapidly progressive clinical course and positive RT-QuIC results in both antemortem and postmortem tissue analyses.

Introduction: Pathogenic variants in ADCY5 cause mixed hyperkinetic movement disorders (MxMD-ADCY5) that can be occasionally refractory to medical treatment. While deep brain stimulation of the globus pallidus internus (GPi-DBS) has been previously used, knowledge on its indication, efficacy and safety is poor and mainly based on anecdotal reports and short case series.

Methods: We retrospectively reviewed clinical, genetic, therapeutic, and surgical data from patients with ADCY5-related movement disorders who underwent GPi-DBS, operated in two French expert centres or previously published.

Results: We obtained data from 23 patients for analysis. There were two distinct indications for GPi-DBS. The first group consisted of patients with long-standing, pharmacoresistant hyperkinetic movements. The second group included patients with acute motor exacerbations - fulfilling criteria for status dystonicus - and conceptually aligned with the recently proposed framework of severe acute motor exacerbation (SAME). Overall, GPi-DBS was safe and led to mild-to-moderate improvement of the motor condition in the two groups of patients.

Conclusion: GPi-DBS can be considered as a relevant therapeutic option for MxMD-ADCY5 in case of pharmacological treatment failure both in patients with chronic motor impairment and those with paroxysmal exacerbations meeting criteria for SAME. Given the response to DBS in the two groups of patients, it is plausible that MxMD-ADCY5 reflects basal ganglia dysfunction mediated by dysregulated cAMP signalling, and that DBS acts by restoring homeostatic inhibitory control in these circuits.

Objective: Migraine is a prevalent neurological disorder, yet its pathophysiology remains incompletely understood. While the role of neuroinflammation and metabolic dysregulation in migraine pathogenesis is increasingly recognized, the kynurenine pathway has gained attention due to its involvement in tryptophan metabolism. Our study aims to evaluate the relationship between kynurenine metabolism, the clinical characteristics of migraine, and the process of migraine chronification.

Materials and methods: This study was designed as a prospective, observational study and was conducted with a total of 81 participants including 27 with episodic migraines, 27 with chronic migraines, and 27 healthy controls, aged 18-50years. Data collected included age, sex, pain type and location of migraine, attack frequency, severity, disease duration, and body mass index. Blood samples taken during the interictal phase were analyzed for Tryptophan (TRP), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid dioxygenase (3-HAAO) levels using ELISA kits.

Results: In the comparison between healthy controls and migraine groups, age, sex, and body mass index were similar. However, the patient group exhibited significantly lower levels of Trp, KYN, 3-HK, and 3-HAAO compared to the control group (P<0.001 for each). Laboratory analysis revealed higher levels of HAAO, 3-HK, KYN, and Trp in the episodic migraine group than in the chronic migraine group (Pp=0.027, P<0.001, P<0.001, P=0.002, respectively). ROC analysis revealed that 3-HK was identified as an independent risk factor for CM (OR=0.403, P<0.001). Painful headache days, monthly attack frequency, MIDAS, and HIT-6 scores were negatively correlated with HAAO, 3-HK, KYN, and Trp levels (P<0.005 for each).

Conclusions: The study suggests that all four molecules are potentially involved in migraine clinical features and its chronification. Their levels decrease as migraine attacks worsen due to their neuroprotective effects. Future studies should explore targeted therapies to modulate kynurenine metabolism to prevent chronic migraine.

Background: Central insulin resistance has been implicated in the pathophysiology of Alzheimer's disease (AD), supporting the hypothesis that, in some individuals, AD may represent "type 3 diabetes." Intranasal insulin has been proposed as a non-invasive approach to enhance brain insulin signaling while minimizing peripheral metabolic effects, but clinical evidence remains inconsistent.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intranasal insulin with placebo in patients with mild cognitive impairment (MCI) or mild-to-moderate AD. Primary outcomes included changes in cognitive performance (ADAS-Cog13, CDR-SB, DSRS, delayed recall) and functional ability (ADCS-ADL). Secondary outcomes included cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau) and safety endpoints. Literature searches were performed in PubMed, Embase, and Cochrane Central up to April 2025. Random-effects models were used to pool effect estimates, and risk of bias was assessed using the Cochrane RoB 2 tool.

Results: Five RCTs enrolling 540 participants met the inclusion criteria. Pooled analyses showed no significant differences between intranasal insulin and placebo for ADAS-Cog13 (mean difference: -1.09 [95% CI: -4.89; 2.71]), ADCS-ADL (mean difference 0.06 [-0.33; 0.45]), CDR-SB, DSRS, or delayed recall. No significant effects were observed on CSF Aβ42, total tau, or p-tau181. Gastrointestinal adverse events were more frequent with insulin (risk ratio: 1.57; [95% CI: 1.15; 2.14]), whereas cardiovascular events were less frequent (risk ratio: 0.30 [0.12; 0.79]). No differences were found for other safety outcomes, and discontinuation rates were comparable between groups.

Conclusion: Intranasal insulin was generally well tolerated but did not produce meaningful improvements in cognitive, functional, or biomarker outcomes in patients with MCI or mild-to-moderate AD. Current evidence does not support its routine clinical use, and further trials with standardized dosing, longer follow-up, and biomarker-stratified designs are warranted to clarify its therapeutic potential.

Late-onset epilepsy of unknown origin (LOEU) is a prevalent and disabling condition. Emerging evidence suggests a potential link between LOEU and new-onset dementia. Cerebral small vessel disease (cSVD) is a common pathology and a major risk factor for both stroke and dementia. cSVD has been hypothesized to contribute to the development of LOEU and cognitive decline through blood-brain barrier dysfunction. This review summarizes current data exploring the association between LOEU and cSVD, highlighting conflicting results, probably due to major methodological limitations. Furthermore, in individuals over 60 years of age conditions such as obstructive sleep apnea (OSA), amyloidopathy, and tauopathy are frequently observed and independently associated with both LOEU and cSVD. To date, no robust evidence has established cSVD as a causal factor of LOEU. The complex interplay of these conditions necessitates further investigation to quantify the contribution of each pathology to the development of LOEU. Future studies using rigorous methodologies are required to determine whether cSVD acts as a primary trigger or merely represents a bystander in LOEU.

Introduction: Migraine severity is often assessed by attack frequency, but this single dimension fails to reflect the full burden of disease. We aimed to validate a pragmatic multidimensional definition of severe migraine in a tertiary care setting.

Methods: We conducted an observational study including 96 consecutive adult migraine patients diagnosed according to ICHD-3 criteria at a tertiary pain center (Marseille, January-April 2024). Data collected included migraine days/month, HIT-6, MIGSEV, and HAD scores. Patients were categorized by frequency (<8 vs. ≥8days/month), HIT-6 (<60, 60-64,≥65), and MIGSEV grades (1-3).

Results: Median monthly frequency was 8days. Patients with≥8days/month had significantly higher HIT-6 scores (P=0.044). Among patients with<8days/month, both HIT-6≥65 and MIGSEV grade 3 identified individuals with greater functional disability and higher depressive symptoms, comparable to those in the high-frequency group. No demographic or comorbidity variables significantly distinguished severe cases.

Discussion: A multidimensional definition of severe migraine is supported: (A)≥8days/month, or (B)<8days/month with HIT-6≥65 and/or MIGSEV grade 3. This definition integrates frequency, functional impact, and perceived severity, providing a simple and reproducible framework to identify high-burden patients. It may improve preventive treatment decisions, referral to specialized care, and harmonization of research inclusion criteria.

The burden of cluster headache (CH) requires better knowledge of management to improve it.

Objectives: To describe changes in the real-world management of CH treated with subcutaneous sumatriptan and/or oxygen in France over the period 2014-2024.

Methods: This is an analysis of two open data databases from the French Social Health Insurance ('Open Medic' and 'Open LPP'), providing an annual estimate from 2014 to 2024 of the delivery of subcutaneous sumatriptan and/or oxygen, the number of beneficiaries of these treatments and their socio-demographic profile.

Results: Annual deliveries of subcutaneous sumatriptan increased from 286,999 boxes in 2014 to 454,275 boxes in 2024 (58.2% increase). Beneficiaries of subcutaneous sumatriptan increased from 13,638 individuals in 2014 to 19,109 individuals in 2024 (40.1% increase). Annual deliveries of package for the weekly use of oxygen therapy equipment increased from 224,143 in 2014 to 790,768 in 2024 (2.5 times more). Beneficiaries of oxygen for CH increased from 7493 individuals in 2014 to 22,346 individuals in 2024 (2 times more). Over the period 2014-2024, the male to female ratio decreased from 2.3/1 to 1.5/1 and from 1.5/1 to 0.8/1 for individuals receiving subcutaneous sumatriptan and individuals receiving oxygen respectively.

Conclusions: The delivery of subcutaneous sumatriptan and oxygen increased from 2014 to 2024, reflecting an improvement in the management of cluster headache in France. Nevertheless, given the one year-prevalence of this disease and the number of people expected to suffer from it, the number of people benefiting from these two treatments in 2024 indicates that there are still unmet needs. This study confirms the increase in the number of women treated for cluster headache observed over the last twenty years.