Annonaceae Consumption Worsens Disease Severity and Cognitive Deficits in Degenerative Parkinsonism.

BACKGROUND: High consumption of Annona muricata fruit has been previously identified as a risk factor for atypical parkinsonism in the French Caribbean islands. OBJECTIVE: We tested whether consumption of Annonaceae products could worsen the clinical phenotype of patients with any form of degenerative parkinsonism. METHODS: We analyzed neurological data from 180 Caribbean parkinsonian patients and specifically looked for dose effects of lifelong, cumulative Annonaceae consumption on cognitive performance. Using unsupervised clustering, we identified one cluster with mild/moderate symptoms (N = 102) and one with severe symptoms including cognitive impairment (N = 78). RESULTS: We showed that even low cumulative consumption of fruits/juices (>0.2 fruit-years) or any consumption of herbal tea from Annonaceae worsen disease severity and cognitive deficits in degenerative parkinsonism including Parkinson's disease (OR fruits-juices: 3.76 [95% CI: 1.13-15.18]; OR herbal tea: 2.91 [95% CI: 1.34-6.56]). CONCLUSION: We suggest that more restrictive public health preventive recommendations should be made regarding the consumption of Annonaceae products. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Impact of Smoking on Functional Prognosis after Ischemic Stroke according to Deprivation: A Prospective Cohort Study.

BACKGROUND: Smoking influence on poststroke prognosis remains controversial. These conflicting results could be due to some residual confounding factors not fully considered in previous studies, including social deprivation. This study aimed to assess the joint impact of deprivation and smoking on functional outcomes after ischemic stroke. METHODS: Between 2011 and 2014, 1,573 patients with a first-ever stroke were prospectively included in the French multicenter INDIA ("Inegalites sociales et pronostic des accidents vasculaires cerebraux à Dijon et Antilles-Guyane") cohort study. Patients with ischemic stroke and available data on smoking, deprivation, and outcome were considered for the analysis (n = 1,242). Deprivation was assessed using the EPICES "Evaluation de la Précarité et des Inégalites de santé dans les Centres d'Examen de Santé" score. Primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) score at 12 months. Association between smoking and moderate to severe disability (mRS score ≥3) was evaluated with logistic regression model. Interactions between smoking and deprivation were tested. RESULTS: Smokers (n = 189, 15.2%) were younger and more often deprived (EPICES score ≥30.17) than nonsmokers. A significant interaction was found between smoking status and deprivation on disability (p = 0.003). In nondeprived patients, the odds of moderate to severe disability at 12 months were twice as high in smokers as in nonsmokers (adjusted OR = 2.08, 95% CI: 1.04-4.18). This association was not observed in deprived patients (adjusted OR = 0.89, 95% CI: 0.49-1.61). CONCLUSION: The effect of smoking on functional prognosis after ischemic stroke varied according to deprivation status, with poorer outcomes observed in nondeprived patients.

Olfactory outcomes in Zika virus-associated Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Zika virus (ZIKV) infection has been associated with Guillain-Barré syndrome (GBS). However, little is known about the consequence of ZIKV infection on olfaction in humans. METHODS: Immediately before the COVID-19 outbreak, we prospectively investigated the olfactory capacities of 19 patients with ZIKV-associated GBS from the French West Indies and compared them to nine controls from the same population, with GBS of similar severity but independent of ZIKV infection. To provide further evidence that ZIKV infection induces smell alteration, we investigated the consequences of ZIKV infection on olfactory abilities using a mouse model. RESULTS: Patients with GBS-ZIKA+ had poorer olfactory function than GBS-non-ZIKA, even 1-2 years after the acute phase. The proportion of patients with hyposmia was significantly higher in the GBS-ZIKA+ than in the GBS-non-ZIKA group (68.4% vs. 22.2%, p = 0.042). These deficits were characterized by lower threshold and identification scores and were independent from GBS severity. Additionally, ZIKV infection was found to impair olfaction in immunodeficient mice infected with ZIKV. High viral load was observed in their olfactory system and downstream brain structures. ZIKV promoted both cellular damage in the olfactory neuroepithelium and protracted inflammation of the olfactory bulb, likely accounting for smell alteration. CONCLUSIONS: Patients with ZIKV-related GBS had poorer long-term olfactory function than patients with GBS-non-ZIKA, and ZIKV-infected mice are hyposmic. These observations suggest that ZIKV belongs on the list of viruses affecting the olfactory system. Clinical evaluation of the olfactory system should be considered for ZIKV-infected patients.

Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.

Acute cerebellar ataxia and myoclonus with or without opsoclonus: a para-infectious syndrome associated with COVID-19.

BACKGROUND AND PURPOSE: Patients with COVID-19 can have central or peripheral neurological manifestations. METHODS: The cases of two patients with acute cerebellar ataxia and myoclonus associated with COVID-19 are reported (with Video S1) and five previously reported patients are discussed. RESULTS: Acute cerebellar ataxia and myoclonus started between 10 days and 6 weeks after the first manifestations of COVID-19. Opsoclonus or ocular flutter was present in four patients. Patients were treated with intravenous immunoglobulins and/or steroids except for one patient, resulting in a striking improvement within a week. CONCLUSION: Acute cerebellar ataxia and myoclonus with or without opsoclonus belongs to the wide spectrum of neurological manifestations associated with COVID-19. It is important to recognize this possible manifestation since early treatment allows for rapid recovery.

Social deprivation and 1-year survival after stroke: a prospective cohort study.

BACKGROUND: Social deprivation may have a deleterious influence on post-stroke outcomes, but available data in the literature are mixed. AIM: The aim of this cohort study was to evaluate the impact of social deprivation on 1-year survival in patients with first-ever stroke. METHODS: Social deprivation was assessed at individual level with the EPICES score, a validated multidimensional questionnaire, in 1312 patients with ischemic stroke and 228 patients with spontaneous intracerebral hemorrhage, who were prospectively enrolled in six French study centers. Baseline characteristics including stroke severity and pre-stroke functional status were collected. Multivariable Cox models were generated to evaluate the associations between social deprivation and survival at 12 months in ischemic stroke and intracerebral hemorrhage separately. RESULTS: A total of 819 patients (53.2%) were socially deprived (EPICES score ≥ 30.17). In ischemic stroke, mortality at 12 months was higher in deprived than in non-deprived patients (16% vs. 11%, p = 0.006). In multivariable analyses, there was no association between deprivation and death occurring within the first 90 days following ischemic stroke (adjusted hazard ratio [aHR] 0.81, 95% CI 0.54-1.22, p = 0.32). In contrast, an excess in mortality was observed between 90 days and 12 months in deprived compared with non-deprived patients (aHR 1.97, 95% CI 1.14-3.42, p = 0.016). In patients with intracerebral hemorrhage, mortality at 12 months did not significantly differ according to deprivation status. CONCLUSIONS: Social deprivation was associated with delayed mortality in ischemic stroke patients only and, although the exact underlying mechanisms are still to be identified, our findings suggest that deprived patients in particular may benefit from an optimization of post-stroke care.

Chikungunya, a Risk Factor for Guillain-Barré Syndrome.

In a matched case-control study where 24 cases developed Guillain-Barré syndrome (GBS) during the 2014 chikungunya outbreak in the French West Indies and 72 controls were blood donors during the same period, chikungunya infection was a risk factor for GBS (odds ratio, 8.3; 95% confidence interval, 2.3-29.7; P = .001).

Neurocognitive impacts of arbovirus infections.

Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.

Telerehabilitation for Stroke Survivors: Systematic Review and Meta-Analysis.

BACKGROUND: Telerehabilitation is an emerging technology through which medical rehabilitation care can be provided from a distance. OBJECTIVE: This systematic review and meta-analysis aims to investigate the efficacy of telerehabilitation in poststroke patients. METHODS: Eligible randomized controlled trials (RCTs) were identified by searching MEDLINE, Cochrane Central, and Web of Science databases. Continuous data were extracted for relevant outcomes and analyzed using the RevMan software as the standardized mean difference (SMD) and 95% CI in a fixed-effect meta-analysis model. RESULTS: We included 15 studies (1339 patients) in our systematic review, while only 12 were included in the pooled analysis. The combined effect estimate showed no significant differences between the telerehabilitation and control groups in terms of the Barthel Index (SMD -0.05, 95% CI -0.18 to 0.08), Berg Balance Scale (SMD -0.04, 95% CI -0.34 to 0.26), Fugl-Meyer Upper Extremity (SMD 0.50, 95% CI -0.09 to 1.09), and Stroke Impact Scale (mobility subscale; SMD 0.18, 95% CI -0.13 to 0.48]) scores. Moreover, the majority of included studies showed that both groups were comparable in terms of health-related quality of life (of stroke survivors), Caregiver Strain Index, and patients' satisfaction with care. One study showed that the cost of telerehabilitation was lower than usual care by US $867. CONCLUSIONS: Telerehabilitation can be a suitable alternative to usual rehabilitation care in poststroke patients, especially in remote or underserved areas. Larger studies are needed to evaluate the health-related quality of life and cost-effectiveness with the ongoing improvements in telerehabilitation networks.

Factors influencing prognosis and functional outcome one year after a first-time stroke in a Caribbean population.

OBJECTIVE: To evaluate functional outcome and quality of life 1 year poststroke in a Caribbean population. DESIGN: Prospective study of patients with a first hemispheric stroke admitted consecutively between December 2010 and February 2011. The patients were evaluated (1) in the emergency department, (2) when discharged from the hospital, and (3) 1 year poststroke. SETTING: A university hospital. PARTICIPANTS: Of the 140 consecutive patients with stroke, 78 (42% women, 24.4% hemorrhagic stroke) were included in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Patients were evaluated using the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), FIM, and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: The mean age of the participants was 62.1±17.7 years; 70.5% of patients had hypertension, 29.4% had diabetes, and 23.6% had chronic renal failure. At 1 year poststroke, the mortality rate was 29.4%, and the recurrence rate 2.6%. We evaluated 39 of the 55 survivors (71%). Score evolution (emergency department vs 1y later) is as follows: for the NIHSS, it was 6.2±4.9 versus 3.3±3.9 (z=-3.578; P<.001); and for the mRS score ≤2, it was 54.2% versus 66.7% (χ(2)=14.182; P=.25). The FIM score on discharge from the hospital versus 1 year later was 103.2±28.2 versus 101.7±31.5 (z=-1.008; P=.313). Multivariate analysis showed that aphasia, hemianopia, and incontinence significantly influenced the 1-year FIM score (P<.001). Quality of life, a patient-reported outcome measure of health-related quality of life, was significantly altered concerning vitality, role physical, and role emotional. CONCLUSIONS: One year after a first stroke, despite significant improvement of neurologic impairment, the level of dependency did not change and quality of life was altered. Aphasia, hemianopia, and incontinence significantly influenced functional state.

Initiation of mechanical thrombectomy in an insular setting with helicopter transfer: a 2-year experience from the first, complete, tertiary stroke center in the Caribbean.

BACKGROUND: This is the first cohort study of patients treated with mechanical thrombectomy (MT) for acute ischemic stroke in the French West Indies, with a mothership center and helicopter transfer. OBJECTIVE: To describe the population and to evaluate imaging, clinical, and time metric outcomes, in order to assess the feasibility and adjust the territorial organization. METHODS: In this observational study, we retrospectively analyzed our prospectively collected data of a population of consecutive patients treated with MT for anterior and posterior circulation large vessel occlusions. Primary outcome was 3-month functional independence (modified Rankin Scale score ≤2). Secondary outcomes included aerial and terrestrial times of arrival, in-hospital delays, demographics, imaging and clinical data at onset, discharge, and at 3 months. We compared the results of the mothership and drip-and-ship paradigms. RESULTS: Between January 2020 and December 2021, 223 patients were included (74% mothership, 26% drip-and-ship). Mean National Institutes of Health Stroke Scale (NIHSS) score of the population was 16 before MT, with significant reduction (NIHSS score 6) at discharge (9 mothership, 12 drip-and-ship, P=0.025). There was significant difference in onset-to-operation room times among the two centers (335 min mothership, 500 min drip-and-ship, P=0.004). Successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b-3) was 80.3%. Functional independence at 3 months was 35%, symptomatic intracranial hemorrhage was 11%, and the complication rate was 9.4%, all without statistically significant difference between the two groups. CONCLUSION: The population has distinct risk factors. MT with helicopter transfer is feasible in the French West Indies. Reduction of prehospital and in-hospital times is mandatory; evaluation of the territorial strategy is underway, to avoid over-selection of transferred patients.

The Pesticide Chlordecone Promotes Parkinsonism-like Neurodegeneration with Tau Lesions in Midbrain Cultures and C. elegans Worms.

Chlordecone (CLD) is an organochlorine pesticide (OCP) that is currently banned but still contaminates ecosystems in the French Caribbean. Because OCPs are known to increase the risk of Parkinson's disease (PD), we tested whether chronic low-level intoxication with CLD could reproduce certain key characteristics of Parkinsonism-like neurodegeneration. For that, we used culture systems of mouse midbrain dopamine (DA) neurons and glial cells, together with the nematode C. elegans as an in vivo model organism. We established that CLD kills cultured DA neurons in a concentration- and time-dependent manner while exerting no direct proinflammatory effects on glial cells. DA cell loss was not impacted by the degree of maturation of the culture. The use of fluorogenic probes revealed that CLD neurotoxicity was the consequence of oxidative stress-mediated insults and mitochondrial disturbances. In C. elegans worms, CLD exposure caused a progressive loss of DA neurons associated with locomotor deficits secondary to alterations in food perception. L-DOPA, a molecule used for PD treatment, corrected these deficits. Cholinergic and serotoninergic neuronal cells were also affected by CLD in C. elegans, although to a lesser extent than DA neurons. Noticeably, CLD also promoted the phosphorylation of the aggregation-prone protein tau (but not of α-synuclein) both in midbrain cell cultures and in a transgenic C. elegans strain expressing a human form of tau in neurons. In summary, our data suggest that CLD is more likely to promote atypical forms of Parkinsonism characterized by tau pathology than classical synucleinopathy-associated PD.

Brain dysfunction in gait disorders of Caribbean atypical Parkinsonism and progressive supranuclear palsy patients: A comparative study.

INTRODUCTION: Gait disorders and falls occur early in progressive supranuclear palsy (PSP-RS) and Caribbean atypical parkinsonism (Caribbean AP). However, the link between these signs and brain lesions has never been explored in these patient populations. Here, we investigate and compare the imaging factors that relate to gait and balance disorders in Caribbean AP and PSP-RS patients. METHODS: We assessed gait and balance using clinical scales and gait recordings in 16 Caribbean AP and 15 PSP-RS patients and 17 age-matched controls. We measured the grey and white matter brain volumes on 3 T brain MRI images. We performed a principal component analysis (PCA) including all the data to determine differences and similarities between groups, and explore the relationship between gait disorders and brain volumes. RESULTS: Both Caribbean AP patients and PSP-RS have marked gait and balance disorders with similar severity. In both groups, gait and balance disorders were found to be most strongly related to structural changes in the lateral cerebellum, caudate nucleus, and fronto-parietal areas. In Caribbean AP patients, gait disorders were also related to additional changes in the cortex, including frontal, insular, temporal and cuneus lobes, whereas in PSP-RS patients, additional white matter changes involved the mesencephalon and parahippocampal gyrus. CONCLUSION: Gait and balance disorders in Caribbean AP patients are mainly related to dysfunction of cortical brain areas involved in visuo-sensorimotor processing and self-awareness, whereas these signs mainly result from premotor-brainstem-cerebellar network dysfunction in PSP-RS patients, brain areas involved in initiation and maintenance of locomotor pattern and postural adaptation.

Endemic parkinsonism: clusters, biology and clinical features.

The term 'endemic parkinsonism' refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region; one in the Caribbean islands of Guadeloupe and Martinique; and four in Europe. Some of these disease entities seem to be disappearing over time and therefore are probably triggered by unique environmental factors. By contrast, other types persist because they are exclusively genetically determined. Given the geographical clustering and potential overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism. Knowledge obtained from the study of these disease entities supports the hypothesis that both genetic and environmental factors contribute to the development of neurodegenerative diseases, not only in endemic parkinsonism but also in general. At the same time, this understanding suggests useful directions for further research in this area.

The microbiome-nose-brain axis in health and disease.

Growing evidence implicates the bacterial populations in the nose as an important factor for personal and global health. Here, we provide a brief overview of the nasal microbiome and speculate on its potential roles in olfactory processing and neurodegeneration, with a particular focus on Parkinson's disease (PD).

Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females.

Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation.

Magnetic resonance imaging lesion pattern in Guadeloupean parkinsonism is distinct from progressive supranuclear palsy.

In the Caribbean island of Guadeloupe, patients with atypical parkinsonism develop a progressive supranuclear palsy-like syndrome, named Guadeloupean parkinsonism. Unlike the classical forms of progressive supranuclear palsy, they develop hallucinations and myoclonus. As lesions associated with Guadeloupean parkinsonism are poorly characterized, it is not known to what extent they differ from progressive supranuclear palsy. The aim of the present study was to determine the structural and metabolic profiles of Guadeloupean parkinsonism compared with progressive supranuclear palsy and controls using combined structural and diffusion magnetic resonance imaging and magnetic resonance spectroscopy. We included 9 patients with Guadeloupean parkinsonism, 10 with progressive supranuclear palsy and 9 age-matched controls. Magnetic resonance imaging examination was performed at 1.5 T and included 3D T(1)-weighted and fluid-attenuated inversion recovery images, diffusion tensor imaging and single voxel magnetic resonance spectroscopy in the lenticular nucleus. Images were analysed using voxel-based morphometry, voxel-based diffusion tensor imaging and brainstem region of interest measurements. In patients with Guadeloupean parkinsonism, structural and diffusion changes predominated in the temporal and occipital lobes, the limbic areas (medial temporal, orbitofrontal and cingulate cortices) and the cerebellum. In contrast to patients with progressive supranuclear palsy, structural changes predominated in the midbrain and the basal ganglia and diffusion abnormalities predominated in the frontocentral white matter, the basal ganglia and the brainstem. Compared with controls, the N-acetylaspartate to creatinine ratio was decreased in patients with progressive supranuclear palsy and to a lesser extent in patients with Guadeloupean parkinsonism. The pattern of structural and diffusion abnormalities differed between progressive supranuclear palsy and Guadeloupean parkinsonism. Widespread cortical atrophy was observed in patients with Guadeloupean parkinsonism who presented marked cognitive changes and hallucinations, whereas midbrain lesions were less severe than in progressive supranuclear palsy. Midbrain (progressive supranuclear palsy) or cortical (Guadeloupean parkinsonism) atrophy was a distinctive neuroimaging feature for differential diagnosis.

Treatable Hyperkinetic Movement Disorders Not to Be Missed.

Hyperkinetic movement disorders are characterized by the presence of abnormal involuntary movements, comprising most notably dystonia, chorea, myoclonus, and tremor. Possible causes are numerous, including autoimmune disorders, infections of the central nervous system, metabolic disturbances, genetic diseases, drug-related causes and functional disorders, making the diagnostic process difficult for clinicians. Some diagnoses may be delayed without serious consequences, but diagnosis delays may prove detrimental in treatable disorders, ranging from functional disabilities, as in dopa-responsive dystonia, to death, as in Whipple's disease. In this review, we focus on treatable disorders that may present with prominent hyperkinetic movement disorders.