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Cerebrotendinous xanthomatosis (CTX) is a rare but treatable inherited neurometabolic disorder that can lead to severe sequelae if left untreated. Chenodeoxycholic acid is a safe and effective treatment for CTX. Early diagnosis is essential to improve patient outcomes. Neurological disturbances, cataracts, and intractable diarrhea are key features to raise diagnostic suspicion and differentiate CTX from other metabolic disorders in patients with dyslipidemia and xanthomas. The diagnosis of CTX depends on high cholestanol plasma levels, undetectable plasma bile acids, neuroradiological findings, and CYP27A1 gene analysis. This review provides a stepwise approach to diagnosing patients with CTX, aims to improve physician awareness of CTX, and highlights the effectiveness of chenodeoxycholic acid as the standard of care. In addition, we report a unique case of CTX with major premature cardiovascular events, initially misdiagnosed as heterozygous familial hypercholesterolemia. This review also provides evidence to establish the c.470T>C (p. Leu157Pro) variant of the CYP27A1 gene as a likely pathologic variant.

Iron deposition in the substantia nigra has been implicated in Parkinson’s disease. Chelation with deferiprone reduced brain iron content but led to worse scores on scales of the movement disorder at 36 weeks.

Objective Because of its heterogeneity in clinical presentation and course, predicting autoimmune encephalitis (AIE) evolution remains challenging. Hence, our aim was to explore the correlation of several biomarkers with the clinical course of disease. Methods Thirty‐seven cases of AIE were selected retrospectively and divided into active (N = 9), improved (N = 12) and remission (N = 16) AIE according to their disease evolution. Nine proteins were tested in both serum and cerebrospinal fluid (CSF) at diagnosis (T0) and during the follow‐up (T1), in particular activated MMP‐9 (MMP‐9A) and YKL‐40 (or chitinase 3‐like 1). Results From diagnosis to revaluation, AIE remission was associated with decreased YKL‐40 and MMP‐9A levels in the CSF, and with decreased NfL and NfH levels in the serum. The changes in YKL‐40 concentrations in the CSF were associated with (1) still active AIE when increasing >10% (P‐value = 0.0093); (2) partial improvement or remission when the changes were between +9% and −20% (P‐value = 0.0173); and remission with a reduction > −20% (P‐value = 0.0072; overall difference between the three groups: P‐value = 0.0088). At T1, the CSF YKL‐40 levels were significantly decreased between active and improved as well as improved and remission AIE groups but with no calculable threshold because of patient heterogeneity. Conclusion The concentration of YKL‐40, a cytokine‐like proinflammatory protein produced by glial cells, is correlated in the CSF with the clinical course of AIE. Its introduction as a biomarker may assist in following disease activity and in evaluating therapeutic response. In this cohort of various types of autoimmune encephalitis (AIE), we showed that the levels of cytokine‐like YKL‐40 in the CSF correlated with the clinical course. From diagnosis (T0) to re‐evaluation point (T1), CSF YKL‐40 levels were increased by more than 10% when AIE was still active, remained stable (between +9% and −20%) when AIE was only partially improved, and decreased by more than 20% in case of complete remission. YKL‐40 could thus be useful for the follow‐up of these rare diseases and for the management of the treatment.

Background Multiple system atrophy (MSA) is characterized by progressive autonomic/motor dysfunction, but robust biomarkers do not exist. Electrochemical skin conductance (ESC) provides a noninvasive measure of sudomotor function, but its longitudinal predictive value and prognostic relevance in MSA remain insufficiently studied. We aimed to comprehensively evaluate ESC in a large longitudinal cohort. Methods We analyzed 175 patients with MSA followed for a mean of 4.2 ± 2.1 years. Disease severity was assessed using UMSARS Parts 1 and 2, COMPASS31, SCOPA‐AUT, and orthostatic blood pressure (BP) measurements. Hand and foot ESC were measured using Sudoscan. Cross‐sectional and longitudinal associations were examined using linear mixed‐effects models, repeated‐measures correlations, and grouped 10‐fold cross‐validation. Mortality predictors were assessed with time‐varying Cox proportional hazards models. Results ESC was strongly inversely associated with UMSARS 1 and 2 (β = −0.58 to −0.65; r = −0.67 to −0.75; all p < 0.0001), whereas associations with orthostatic BP, autonomic symptom scales, and disease duration were weaker or inconsistent. ESC declined significantly over time (feet −6.88 ± 0.60 μS/year; hands −5.41 ± 0.46 μS/year; both p < 0.001), paralleling UMSARS progression. ESC outperformed orthostatic BP drops in predicting UMSARS scores in mixed‐effects models and cross‐validation. Higher ESC independently predicted lower mortality, while higher UMSARS scores and greater orthostatic BP drops predicted increased risk. Median survival was 46.2 months. Conclusions ESC is a sensitive biomarker of disease severity, progression, and survival in MSA, substantially outperforming orthostatic BP measures. Its simplicity and prognostic value support incorporation into routine monitoring and clinical trials. In a longitudinal cohort of 175 patients with multiple system atrophy followed for 4.2 years, electrochemical skin conductance (ESC) was strongly associated with disease severity (UMSARS), declined significantly over time, and independently predicted survival. ESC outperformed orthostatic blood pressure drops in tracking progression and predicting clinical outcomes. These findings support ESC as a simple, noninvasive biomarker for monitoring disease progression and as a candidate endpoint for clinical trials.

Effectiveness of Foot Reflexology (FR) on the pain intensity in Parkinson's disease (PD) compared with Sham Massage (SM). Monocentric, longitudinal, prospective, double-blind, randomized controlled trial. Randomization with a random number generator in the R software. Fixed-sized block randomization of 3 implemented into Clinsight. Idiopathic PD patients with chronic pain (Visual Analogue Scale (VAS)≥4) were recruited from the Toulouse University Hospital between the 14th of April 2021 and the 25th of May 2025. Four one-hour long FR or SM sessions three weeks apart with the same specialized FR researcher. Pain intensity change measured by the mean VAS before and after full completed interventions. The difference was compared between group using a Wilcoxon Mann Witney test. Exploratory outcome: brain functional connectivity. 30 PD patients were randomized and analyzed. Interventions were delivered as planned for all patients. Clinical variables did not significantly differed between FR and SM groups. Mean VAS decreased by -12.3 mm ± 15.2 in FR group (n = 15) and -17.9 mm ± 29.4 in SM group (n = 15). Analyses did not reveal any significant difference between the FR and SM groups (p-value = 0.88). There are different patterns in connectivity changes in the medial pain system between responders (at least 30% pain reduction) and non-responders to both therapies. There were no adverse events. FR is not more effective than SM in relieving chronic pain in PD. The differences in connectivity patterns within the medial pain pathway may underlie the response to tactile stimulation (FR and SM). ClinicalTrials.gov NCT04705207.

Wilson disease (WD) treatment aims to reduce copper accumulation in the liver and brain. Zinc salts (ZS) are often associated with gastrointestinal side effects, poor adherence, and reduced efficacy. Copper chelators, such as trientine tetrahydrochloride (TETA4), offer an alternative for patients who are intolerant or unresponsive to ZS. This observational study assesses the long-term efficacy and safety of switching from ZS to TETA4 in twenty WD patients (15 hepatic, 5 hepato-neurological) from the French WD Registry. Treatment goals included normalization of aminotransferases, stabilization or improvement of the liver (APRI, liver stiffness and liver ultrasonography; US) and the neurological (Unified Wilson’s Disease Rating Scale; UWDRS) involvement, Clinical Global Impression (CGI) severity scale, and achievement of copper balance targets. Assessments were performed at baseline and every 6 months for 3 years. Adverse events were recorded throughout the follow-up. The results revealed that the main reasons for switching were gastrointestinal intolerance and loss of efficacy with ZS; 60% had elevated ALT at baseline. TETA4 was initiated at a median dose of 412.5 mg (360–450) and titrated up to 750 mg/day (600–900 mg) to achieve the treatment goals. Over 3 years, no changes were observed in ALT, APRI, liver US, UWDRS and CGI scores. TETA4 was well tolerated. In conclusion, transitioning from ZS to TETA4 maintained clinical stability and adherence with a favorable safety profile. Dose adjustments suggest conversion ratios of ~1:6 elemental zinc.

Background and objectives The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL). Methods Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson’s Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions. Results 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores. Conclusions Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores.

Background Few patients are reported with dementia with Lewy bodies before fifty years-old, which may partly reflect the difficulty of accurate diagnosis in young population. We report the case of a 44-year-old male with pathologically confirmed sporadic dementia with Lewy bodies, who did not fulfil the revised clinical criteria for this disease. Case presentation We document this atypical case with clinical and cognitive evaluation, imaging, biochemistry, genetics and pathology investigations. Creutzfeldt-Jakob disease was first suspected in this patient with no previous medical history, who developed acute and rapid cognitive impairment, L-dopa-non-responsive parkinsonism, and delusion. Positive 14–3–3 protein was initially detected in cerebrospinal fluid and until the late stages of the disease. Severe atrophy with no diffusion hypersignal was found on structural MRI as well as an extensive hypometabolism on 18 F-FDG-PET, in comparison to age-matched healthy volunteers. Genetic investigation found no alpha-synuclein gene mutation. The patient died within 5 years, and post-mortem examination found numerous Lewy bodies and Lewy neurites consistent with pure Lewy body disease. Conclusions This comprehensively described case illustrates that dementia with Lewy bodies can occur in young patients with atypical clinical presentation. Biochemistry and neuroimaging investigations can sometimes be insufficient to allow accurate diagnostic. More specific markers to support such diagnosis are needed.

BackgroundSTUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1 are now considered a frequent cause of cerebellar ataxia.ObjectiveWe aimed to improve the clinical, radiological, and molecular delineation of SCAR16 and SCA48.MethodsRetrospective collection of patients with SCAR16 or SCA48 diagnosed in three French genetic centers (Montpellier, Strasbourg and Nancy).ResultsHere, we report four SCAR16 and nine SCA48 patients from two SCAR16 and five SCA48 unrelated French families. All presented with slowly progressive cerebellar ataxia. Additional findings included cognitive decline, dystonia, parkinsonism and swallowing difficulties. The age at onset was highly variable, ranging from 14 to 76 years. Brain MRI showed marked cerebellar atrophy in all patients. Phenotypic findings associated with STUB1 pathogenic variations cover a broad spectrum, ranging from isolated slowly progressive ataxia to severe encephalopathy, and include extrapyramidal features. We described five new pathogenic variations, two previously reported pathogenic variations, and two rare variants of unknown significance in association with STUB1-related disorders. We also report the first pathogenic variation associated with both dominant and recessive forms of inheritance (SCAR16 and SCA48).ConclusionEven though differences are observed between the recessive and dominant forms, it appears that a continuum exists between these two entities. While adding new symptoms associated with STUB1 pathogenic variations, we insist on the difficulty of genetic counselling in STUB1-related pathologies. Finally, we underscore the usefulness of DAT-scan as an additional clue for diagnosis.

Studies assessing personality dimensions by the \"Temperament and Character Inventory\" (TCI) have previously found an association between Parkinson's disease (PD) and lower Novelty Seeking and higher Harm Avoidance scores. Here, we aimed to describe personality dimensions of PD patients with motor fluctuations and compare them to a normative population and other PD populations. All PD patients awaiting Deep Brain Stimulation (DBS) answered the TCI before neurosurgery. Their results were compared to those of historical cohorts (a French normative population, a de novo PD population, and a PD population with motor fluctuations). Most personality dimensions of our 333 included PD patients with motor fluctuations who are candidates for DBS were different from those of the normative population and some were also different from those of the De Novo PD population, whereas they were similar to those of another population of PD patients with motor fluctuations. During the course of PD, personality dimensions can change in parallel with the development of motor fluctuations, either due to the evolution of the disease and/or dopaminergic treatments.