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Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R 2 ∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R 2 ∗ occurring in Parkinson's disease patients compared to controls, a multicentre transversal study was carried out on a large cohort of Parkinson's disease patients (n = 163) with matched controls (n = 82). In this study, 44 patients and 11 controls were removed due to motion artefacts, 21 patient and 6 controls to preserve matching. Thus, 98 patients and 65 age and sex-matched healthy subjects were selected with enough image quality. The study was conducted on patients with early to late stage Parkinson's disease. The images were acquired at 3Tesla in 12 clinical centres. R 2 ∗ values significantly increased in Parkinson's disease patients when compared with controls; in the substantia nigra (SN) in the dominant side (D) and in the non dominant side (ND), respectively (P 2 ∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R 2 difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R ∗ in the red nucleus as an intra-subject reference. R 2 ∗  < 0.0001) when comparing all Parkinson's disease patients to controls. R SN&#95;D and P SN&#95;ND  < 0.0001). After stratification into four subgroups according to the disease duration, no significant R 2 ∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R 2(ISQR) and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease.∗ values significantly increased in the substantia nigra (P SN&#95;D and P SN&#95;ND  < 0.0001) when comparing all Parkinson's disease patients to controls. R 2(ISQR) ∗ values in the substantia nigra significantly increased with the disease duration (P SN&#95;D  = 0.01; P SN&#95;ND  = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, P SN&#95;D  = 0.02). Additionally, correlations between R 2(ISQR) ∗ and clinical features, mainly related to the severity of the disease, were found. Our results support the use of ISQR to reduce variations not directly related to Parkinson's disease, supporting the concept that ISQR strategy is useful for the evaluation of Parkinson's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Diagnosis of inherited ataxia and related diseases represents a real challenge given the tremendous heterogeneity and clinical overlap of the various causes. We evaluated the efficacy of molecular diagnosis of these diseases by sequencing a large cohort of undiagnosed families., Methods: We analyzed 366 unrelated consecutive patients with undiagnosed ataxia or related disorders by clinical exome-capture sequencing. In silico analysis was performed with an in-house pipeline that combines variant ranking and copy-number variant (CNV) searches. Variants were interpreted according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines., Results: We established the molecular diagnosis in 46% of the cases. We identified 35 mildly affected patients with causative variants in genes that are classically associated with severe presentations. These cases were explained by the occurrence of hypomorphic variants, but also rarely suspected mechanisms such as C-terminal truncations and translation reinitiation., Conclusion: A significant fraction of the clinical heterogeneity and phenotypic overlap is explained by hypomorphic variants that are difficult to identify and not readily predicted. The hypomorphic C-terminal truncation and translation reinitiation mechanisms that we identified may only apply to few genes, as it relies on specific domain organization and alterations. We identified PEX10 and FASTKD2 as candidates for translation reinitiation accounting for mild disease presentation., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Background: Bilateral subthalamic nucleus deep brain stimulation improves motor symptoms and treatment-related complications in patients with Parkinson's disease. However, some patients have trouble adjusting socially after successful neurosurgery, in part because of "unrealistic" expectations and psychiatric disorders. Preoperative psychological interventions focusing on these aspects could be beneficial for such patients., Methods: We compared the outcomes of 2 psychosocial approaches-1 based on cognitive restructuration and 1 consisting of 2 interviews-with those of a control group without preoperative preparation. All patients underwent a psychometric evaluation 2 months before surgery (M-2) and again at 3 (M+3) and 6 months (M+6) after surgery. The psychometric evaluation focused on social adjustment using the social adjustment scale-self-report. The psychiatric profile of the patients was also assessed., Results: Of 73 patients initially enrolled, 62 performed the initial inclusion visit (M-2) and the 2 postoperative visits (M+3, M+6). For these 62 patients (52% male), the overall mean age was 59 ± 6.13 years, and the mean disease duration was 9.44 ± 3.62 years. No specific differences were observed for social adjustment between the groups or visits (M-2, M+3, M+6); however, an interaction was found in the cognitive restructuration group at M+6 for the family dimension of the social adjustment scale-self-report., Conclusion: Our results suggest that even if no overall increase in the social adjustment score was observed, patients with Parkinson's disease eligible for neurosurgery should undergo preoperative psychosocial therapy to define their expectations and help them in their psychological restructuration. This type of therapy, complementary to psychoeducation, could represent an opportunity to prevent postoperative deception and social maladjustment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ataxia with Oculomotor Apraxia type 2 (AOA2) is one of the most frequent types of autosomal degenerative cerebellar ataxia. The first objective of this work was to identify specific cerebellar atrophy using MRI in patients with AOA2. Since increased iron deposits have been reported in degenerative diseases, our second objective was to report iron deposits signals in the dentate nuclei in AOA2. Five patients with AOA2 and 5 age-matched controls were subjects in a 3T MRI experiment that included a 3D turbo field echo T1-weighted sequence. The normalized volumes of twenty-eight cerebellar lobules and the percentage of atrophy (relative to controls) of the 4 main cerebellar regions (flocculo-nodular, vermis, anterior and posterior) were measured. The dentate nucleus signals using 3D fast field echo sequence for susceptibility-weighted images (SWI) were reported, as a measure of iron content. We found that all patients had a significant atrophy of all cerebellar lobules as compared to controls. The percentage of atrophy was the highest for the vermis, consistent with patients' oculomotor presentation, and for the anterior lobe, consistent with kinetic limb ataxia. We also describe an absence of hypointensity of the iron signal on SWI in the dentate nucleus of all patients compared to control subjects. This study suggests that patients with Ataxia with Oculomotor Apraxia type 2 present MRI patterns consistent with their clinical presentation. The absence of SWI hypointensity in dentate nucleus is a new radiological sign which was identified in all patients. The specificity of this absence of signal must be further determined in AOA2.

Objective: To assess the one-year outcome of patients referred to the emergency room for a first paroxysmal event of clinically certain or uncertain epileptic origin., Methods: This prospective observational cohort study included 175 adult patients who were consecutively referred for a first paroxysmal event and excluding clinically certain syncope faints. Simple descriptive clinical criteria were used by emergency room physicians for epileptic assessment. Follow-up and final diagnosis were made by neurologists specialized in epilepsy. The risk of recurrence and epilepsy over time was described using Kaplan-Meier estimates. The effect of risk factors (including EEG results) was assessed using univariate log-rank tests and a Cox regression multivariate model. Negative and positive predictive values (NPV and PPV) at 1 year of significant factors were calculated., Results: Clinical criteria were positive in 67 patients and negative in 108. At 1 year, the rate of recurrence was respectively 8% in the negative clinical criteria group (NCC) and 30% in the positive clinical criteria group (PCC) (RR=9.3; 95% CI=[1.22; 71.4]). The risk of subsequent epilepsy was respectively 16% in the NCC group and 57% in PCC group (RR=5.6; 95% CI=[2.0; 15.6]). Positive predictive value (PPV) of clinical criteria was 28.8% for recurrence and 57.6% for definite epilepsy. Negative predictive value (NPV) of clinical criteria was 93.2% for recurrence and 83.5% for definite epilepsy. The presence of significant abnormalities on early EEG (paroxysms or focal abnormalities) supported an epileptic origin in 17% of clinically uncertain seizures. It was associated with a higher risk of subsequent epilepsy (RR=2.50; 95% CI [1.37; 4.41]; P=0.007), but did not significantly improve the PPV of clinical criteria alone., Conclusion: These results may help provide a prognosis at 1 year after a first paroxysmal event of certain or uncertain epileptic origin. Future studies focusing on the outcome after a first epileptic seizure should take into consideration the degree of certainty of the clinical diagnosis and integrate the group of patients with uncertain epileptic seizure., (Copyright © 2012. Published by Elsevier SAS.)