Amantadine use in the French prospective NS-Park cohort.

OBJECTIVE: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). BACKGROUND: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. METHODS: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). RESULTS: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. CONCLUSIONS: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs.

Volumetric changes and clinical trajectories in Parkinson's disease: a prospective multicentric study.

BACKGROUND: Longitudinal measures of structural brain changes using MRI in relation to clinical features and progression patterns in PD have been assessed in previous studies, but few were conducted in well-defined and large cohorts, including prospective clinical assessments of both motor and non-motor symptoms. OBJECTIVE: We aimed to identify brain volumetric changes characterizing PD patients, and determine whether regional brain volumetric characteristics at baseline can predict motor, psycho-behavioral and cognitive evolution at one year in a prospective cohort of PD patients. METHODS: In this multicentric 1 year longitudinal study, PD patients and healthy controls from the MPI-R2* cohort were assessed for demographical, clinical and brain volumetric characteristics. Distinct subgroups of PD patients according to motor, cognitive and psycho-behavioral evolution were identified at the end of follow-up. RESULTS: One hundred and fifty PD patients and 73 control subjects were included in our analysis. Over one year, there was no significant difference in volume variations between PD and control subjects, regardless of the brain region considered. However, we observed a reduction in posterior cingulate cortex volume at baseline in PD patients with motor deterioration at one year (p = 0.017). We also observed a bilateral reduction of the volume of the amygdala (p = 0.015 and p = 0.041) and hippocampus (p = 0.015 and p = 0.053) at baseline in patients with psycho-behavioral deterioration, regardless of age, dopaminergic treatment and center. CONCLUSION: Brain volumetric characteristics at baseline may predict clinical trajectories at 1 year in PD as posterior cingulate cortex atrophy was associated with motor decline, while amygdala and hippocampus atrophy were associated with psycho-behavioral decline.

Disappearance of anti-thyroglobulin antibodies from the cerebrospinal fluid in parallel with neurological improvement during treatment for Hashimoto's encephalopathy / Disparition des anticorps anti-thyroglobuline dans le liquide céphalo-rachidien après traitement de l'encéphalopathie de Hashimoto

Abnormal elevation of thyroid antibodies in the CSF is observed in 62-75% of Hashimoto's encephalopathy cases. However, the relationship between CSF thyroid antibody levels and response to therapy has been poorly evaluated. We report the case of a 68-year-old man with Hashimoto's encephalopathy, in whom there was a relation between the favorable clinical outcome and the disappearance of antithyroid antibodies from the CSF and a decrease in serum thyroid antibodies.

Une élévation anormale des anticorps thyroïdiens dans le LCR est observée dans 62 à 75 % des cas d'encéphalopathie de Hashimoto. Cependant, la relation entre les niveaux d'anticorps thyroïdiens dans le LCR et la réponse au traitement a été rarement évaluée. Nous rapportons le cas d'un homme de 68 ans atteint d'encéphalopathie de Hashimoto, chez qui l'évolution clinique favorable sous traitement était associée à la disparition des anticorps antithyroïdiens du LCR et une diminution des anticorps thyroïdiens sériques.

Intrasubject subcortical quantitative referencing to boost MRI sensitivity to Parkinson's disease.

Several postmortem studies have shown iron accumulation in the substantia nigra of Parkinson's disease patients. Iron concentration can be estimated via MRI-R2∗ mapping. To assess the changes in R2∗ 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. R2∗ values were measured in subcortical regions of interest (substantia nigra, red nucleus, striatum, globus pallidus externus and globus pallidus internus) contralateral (dominant side) and ipsilateral (non dominant side) to the most clinically affected hemibody. As the observed inter-subject R2∗ variability was significantly higher than the disease effect, an original strategy (intrasubject subcortical quantitative referencing, ISQR) was developed using the measurement of R2∗ in the red nucleus as an intra-subject reference. R2∗ 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 (PSN_D and PSN_ND < 0.0001). After stratification into four subgroups according to the disease duration, no significant R2∗ difference was found in all regions of interest when comparing Parkinson's disease subgroups. By applying our ISQR strategy, R2(ISQR)∗ values significantly increased in the substantia nigra (PSN_D and PSN_ND < 0.0001) when comparing all Parkinson's disease patients to controls. R2(ISQR)∗ values in the substantia nigra significantly increased with the disease duration (PSN_D = 0.01; PSN_ND = 0.03) as well as the severity of the disease (Hoehn & Yahr scale <2 and ≥ 2, PSN_D = 0.02). Additionally, correlations between R2(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.

Progressive multifocal leukoencephalopathy in patients with immunovirological control and at least 6 months of combination antiretroviral therapy.

OBJECTIVES AND METHODS: : Progressive multifocal leukoencephalopathy (PML) has rarely been reported in people with HIV (PWH) with long-term HIV immune-virological control. We describe the clinical and biological characteristics of patients with confirmed PML among PWH with a CD4+ cell count more than 200 cells/µl and an undetectable HIV RNA viral load after at least 6 months of combined antiretroviral therapy (cART) at the time of PML diagnosis, in the large French multicenter Dat'AIDS cohort. RESULTS: : Among 571 diagnoses of PML reported in the Dat'AIDS cohort between 2000 and 2019, 10 cases (1.75%) occurred in PWH with a CD4+ cell count greater than 200 cells/µl and an undetectable HIV RNA viral load after at least 6 months of cART. Median CD4+ cell count at PML diagnosis was 395 cells/µl (IQR 310-477). The median duration between the last detectable HIV viral load and the PML diagnosis was 41.1 months (IQR 8.2-67.4). Only one patient treated with rituximab-based chemotherapy for a large B-cell lymphoma had an established risk factor for PML. Among the nine other patients with no apparent severe immunodeficiency, multiple factors of impaired immunity could have led to the development of PML: hepatitis C virus (HCV) co-infection (n = 6), cirrhosis (n = 4), HHV-8 co-infection (n = 3) with Kaposi's sarcoma (n = 2) in association with Castleman's disease (n = 1) and indolent IgA multiple myeloma (n = 1). CONCLUSION: : This study highlights that factors other than low CD4+ cell count and high HIV viral load may be associated with the occurrence of PML. Further studies are warranted to investigate in greater detail the immunologic characteristics of PWH with immune-virological control who develop PML.

"Accidental, really?" Attributional bias in patients with Parkinson's disease.

INTRODUCTION: Among the cognitive domains impaired in Parkinson's disease (PD), social cognition has received particular attention in recent years. Nevertheless, attributional bias, a social-cognitive subdomain, has not yet been studied in this population, despite its potential relationship with neuropsychiatric symptoms, and despite the possibility that deep-brain stimulation of the subthalamic nucleus, an effective treatment for disabling motor symptoms, worsens cognitive impairment. The present study therefore compared the attributional bias of patients with PD (stimulated and nonstimulated subgroups) with that of controls. It also explored the potential correlations between patients' attributional bias and their clinical scores. METHODS: Thirty-two patients with PD (12 stimulated and 20 nonstimulated) were recruited and matched with 32 healthy controls. Attributional bias was assessed using the Ambiguous Intentions Hostility Questionnaire, which yields three subscores: Hostility Bias, Aggression Bias, and Blame. Depressive symptoms (Hamilton Rating Scale for Depression), paranoid thoughts (Paranoia Scale), global cognition (Montreal Cognitive Assessment), and social functioning (Social Functioning Questionnaire) were also assessed. RESULTS: Patients exhibited more hostile and aggressive biases than controls, especially in ambiguous situations. Stimulated patients had greater hostility and aggression biases and a higher blame score than controls in accidental situations. No significant differences were observed between stimulated and nonstimulated patients. CONCLUSION: To our knowledge, this is the first study to have assessed attributional bias in patients with PD and explored the impact of deep-brain stimulation on this particular subdomain of social cognition. Results suggest that patients exhibit attributional bias, and this impairment may be exacerbated in stimulated patients.

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study.

BACKGROUND: In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March - mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). METHODS: PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. RESULTS: 2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. CONCLUSIONS: The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .

Descriptive analysis of the French NS-Park registry: Towards a nation-wide Parkinson's disease cohort?

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's. The French clinical research network for PD (NS-Park) has created a national patient registry to i)report medical activity of Parkinson Expert Centers (PECs) to the Ministry of Health, ii)facilitate PD patients pre-screening for clinical trials, iii) provide a source for pharmaco-epidemiology studies. OBJECTIVE: Assess the French Parkinsonian population at a nation-wide level and discover new clinical characteristics. METHODS: In this feasibility study, PECs prospectively collected clinical data in a standardized manner. The population main clinical characteristics are described, focusing on motor and non-motor symptoms and treatments, assessing its representativeness. By using an unbiased clustering with multiple correspondence analysis (MCA), we also investigate potential relationships between multiple variables like symptoms and treatments, as clues for future studies. RESULTS: Between 2012 and 2016, among 11,157 included parkinsonian syndromes, 9454 (85%) had PD. MCA identified various profiles depending on disease duration. Occurrences of motor complications, axial signs, cognitive disorders and Levodopa use increase over time. Neurovegetative symptoms, psychiatric disorders, sleep disturbances and impulse control disorders (ICDs) seem stable over time. As expected, ICDs were associated to dopaminergic agonist use but other associations, such as ICDs and sleep disturbances for instance, or anxiety and depression, were found. CONCLUSIONS: Our results report one of the biggest PD registries ever reported and demonstrate the feasibility of implementing a nation-wide registry of PD patients in France, a potent tool for future longitudinal studies and clinical trials' population selection, and for pharmaco-epidemiology and cost-effectiveness studies.

A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia.

OBJECTIVE: To evaluate the efficacy and safety of zonisamide in patients with myoclonus-dystonia. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial of zonisamide (300 mg/d) in 24 patients with myoclonus-dystonia. Each treatment period consisted of a 6-week titration phase followed by a 3-week fixed-dose phase. The periods were separated by a 5-week washout period. The co-primary outcomes were action myoclonus severity (section 4 of the Unified Myoclonus Rating Scale [UMRS 4]) and myoclonus-related functional disability (UMRS 5). Secondary outcomes included dystonia severity, assessed with the movement and disability subscales of the Burke-Fahn-Marsden-Dystonia Rating Scale (BFM), the Clinical Global Impression-Improvement scale (CGI), and safety measures. Wilcoxon signed-rank tests for paired data were used to analyze treatment effects. RESULTS: Twenty-three patients (11 men, 12 women) were analyzed in the intention-to-treat analysis. Zonisamide significantly improved both action myoclonus (median improvement [95% confidence limits] -5 [-9.25 to -1.44], p = 0.003) and myoclonus-related functional disability (median improvement [95% confidence limits] -2 [-2.58 to -2.46], p = 0.007) compared to placebo. Zonisamide also significantly improved dystonia (BFM movement) compared to placebo (median improvement [95% confidence limits] -3 [-8.46 to 0.03], p = 0.009). No difference was found between zonisamide and placebo with respect to the CGI (median improvement [95% confidence limits] -1 [-1.31 to 0.09], p = 0.1). Zonisamide was well-tolerated. CONCLUSIONS: Zonisamide is well-tolerated and effective on the motor symptoms of myoclonus-dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that zonisamide improves myoclonus and related disability in patients with myoclonus-dystonia.

Systemic Sarcoidosis Mimicking a Behavioural Variant of Frontotemporal Dementia.

Among rare neurological manifestations, a progressive dementia may exceptionally be the revealing clinical feature of a sarcoidosis. Diagnosis may then be difficult, especially when systemic signs are missing or latent, with a risk of therapeutic delay. We report the first case of sarcoidosis mimicking a frontotemporal dementia. A 53-year-old man presented with a dementia clinically suggestive of frontotemporal dementia, progressing slowly for about 2 years. However, MRI revealed unusual aspects, mainly large areas of T2/FLAIR hypersignal within temporal regions and cerebellum, with nodular leptomeningeal and juxtacortical Gadolinium enhancement. The patient was finally diagnosed with a systemic sarcoidosis. We discuss the differential diagnosis based on MRI aspects and review the literature on the clinical, biological, and imaging features of sarcoidosis presenting with dementia. This case demonstrates that brain imaging remains mandatory in the exploration process of a patient with dementia. Although the patient presented with rather typical features of a behavioural variant of frontotemporal dementia, the MRI aspect was the key exploration that leaded to the diagnosis.

Manic episode with psychotic symptoms in a patient with Parkinson's disease treated by subthalamic nucleus stimulation: improvement on switching the target.

Manic symptoms have been reported as adverse effects of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease. In previous reports, manic symptoms were described as transient, not associated with psychotic features, and improved spontaneously or with medical adjustments. The medial part of the STN seems to play a key role in the occurrence of these manic symptoms. We report the case of a manic episode with psychotic symptoms in a patient with Parkinson's disease treated by STN DBS, which improved with a change in the stimulated target. This case demonstrates the efficacy of switching the stimulation target against a manic episode with psychotic features secondary to DBS.

Hallucinations in Parkinson's disease: a follow-up study.

To study prevalence of hallucinations in patients with Parkinson's disease (PD) during a 1-year period, and identify factors predictive of the onset of hallucinations in patients who were hallucination-free at baseline, 141 unselected outpatients with PD were evaluated prospectively for a set of demographic, clinical, and therapeutic variables and the presence of hallucinations during the previous 3 months. Patient groups were compared with nonparametric tests, and logistic regression was applied to significant data. Follow-up data were available for 127 patients. The hallucination prevalence rates (%) at the first and second evaluation were, respectively, 41.7 and 49.6 for hallucinations of all types (NS), 29.1 and 40.2 for minor hallucinations (i.e., presence or passage hallucinations, and illusions) (P = 0.02), 22.8 and 21.2 for formed visual hallucinations (NS), and 8.7 and 8.7 for auditory hallucinations (NS). Hallucinations rarely started or ceased during the study. The most labile forms were minor hallucinations, which developed in 20% of patients and ceased in 9%. During follow-up, 15% of patients started to hallucinate. Three factors, all present at the first evaluation, independently predicted the onset of hallucinations in patients previously free of hallucinations at baseline (odds ratio; 95% confidence interval): severe sleep disturbances (14.3; 2.5-80.9), ocular disorders (9.1; 1.6-52.0), and a high axial motor score (5.7; 1.2-27.4). Hallucinations have a chronic course in most parkinsonian patients. Factors predicting the onset of hallucinations point to a role of extranigral brainstem involvement and a nonspecific, facilitating role of ocular disorders.