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Maria Stamelou - One of the best experts on this subject based on the ideXlab platform.
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how to approach a patient with Parkinsonism red flags for Atypical Parkinsonism
International Review of Neurobiology, 2019Co-Authors: Eoin Mulroy, Maria Stamelou, Kailash P BhatiaAbstract:Abstract Parkinsonism is a clinical syndrome defined by bradykinesia plus rigidity or tremor. Though most commonly encountered in the setting of idiopathic Parkinson's disease, a number of neurodegenerative, structural, metabolic and toxic neurological disorders can result in Parkinsonism. Accurately diagnosing the underlying cause of Parkinsonism is of both therapeutic and prognostic relevance, especially as we enter the era of disease-modifying treatment trials for neurodegenerative disorders. Being aware of the wide array of potential causes of Parkinsonism is of paramount importance for clinicians. In this chapter, we present a pragmatic clinical approach to patients with Parkinsonism, specifically focusing on ‘red flags’, which should alert one to consider diagnoses other than idiopathic Parkinson's disease.
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classification of Atypical Parkinsonism per pathology versus phenotype
International Review of Neurobiology, 2019Co-Authors: Gesine Respondek, Maria Stamelou, Gunter U HoglingerAbstract:The umbrella term "Atypical Parkinsonism" refers to a clinical presentation with various causes, emphasizing the clinical commonality of diseases in which Atypical Parkinsonism can present. This term is useful for describing the phenomenology of a movement disorder and to classify patients according to their clinical presentation. In contrast to this classification per phenotype, a classification per pathology is needed when it comes to understanding the pathogenesis and designing and delivering disease-modifying therapeutic interventions. Clinico-pathological correlation studies have revealed enormous clinical heterogeneity and vast clinical overlap in pathologically defined diseases related to Atypical Parkinsonism. Thus, the classification of patients with Atypical Parkinsonism per phenotype has limited validity for predicting the underlying pathology. This chapter will contrast the phenotype-driven classification and the pathology-driven classification of neurodegenerative diseases related to Atypical Parkinsonism and discuss future directions to improve pathology-specific diagnosis.
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Therapeutic Management of the Overlapping Syndromes of Atypical Parkinsonism
CNS Drugs, 2018Co-Authors: Nikolaos Giagkou, Maria StamelouAbstract:Progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy account for approximately 10% of neurodegenerative Parkinsonism. Considerable clinical overlap exists between these disorders that extends to features considered characteristic of each disease. Clinical diagnostic criteria have attempted to increase the accuracy of clinical diagnosis as accurate diagnosis is necessary to inform prognosis and to facilitate the recognition of disease-modifying treatments. Currently no such treatment exists. Nevertheless, many clinical trials aiming to change the natural history of these diseases are ongoing. The spread and accumulation of abnormal proteins are among the pathophysiological mechanisms targeted. For the time being, however, only symptomatic treatment is available. Levodopa is used to treat Parkinsonism, but patients usually show a poor or transient response. Amantadine is also used in practice for the same indication. Botulinum toxin can alleviate focal dystonic manifestations. Addressing non-motor manifestations is limited by the potential of available drugs to impact on other aspects of the disease. Most of the new symptomatic formulations under study are focused on orthostatic hypotension in multiple system atrophy. Exercise, occupational, physical, and speech therapy and psychotherapy should always accompany pharmacological approaches.
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Atypical Atypical Parkinsonism critical appraisal of a cohort
Parkinsonism & Related Disorders, 2017Co-Authors: Stephanie T Hirschbichler, Maria Stamelou, Roberto Erro, Christos Ganos, Amit Batla, Bettina Balint, Kailash P BhatiaAbstract:Abstract Background Atypical parkinsonian conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and Dementia with Lewy bodies (DLB) comprise 10–15% of parkinsonian syndromes. Misdiagnosis with Parkinson disease (PD) and within the entities is common, given the absence of reliable biomarkers. However a correct diagnosis is not only important in clinical practice, but also crucial for any trial attempting to identify biomarkers or new treatments. Methods Consecutive patients, who were referred to our tertiary center with a diagnosis of a particular AP were included and the medical records were reviewed retrospectively. We applied each set of current diagnostic research criteria to the respective cohort to see which features fit in and if there are any additional Atypical features “outside” the classic definition. Results Sixty-nine patients were recruited between January 2013 and May 2015 clinically presenting with one of the following phenotypes: 14 MSA, 24 PSP, 19 CBS and 12 DLB. Up to 49% showed additional “Atypical” features and approximately 10% eventually received an alternative diagnosis, in half of whom this being based on genetic testing. Conclusions In a subset of our patients, despite the final diagnosis of an AP being maintained, there were additional “Atypical” features. It remains to be seen if these reflect the clinical heterogeneity of APs, or should prompt a search for an alternative diagnosis. The search for biomarkers is more likely to be successful in homogenous groups of “typical” patients, hence the importance of recognizing “Atypical” features.
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nonmotor features in Atypical Parkinsonism
International Review of Neurobiology, 2017Co-Authors: Kailash P Bhatia, Maria StamelouAbstract:Atypical Parkinsonism (AP) comprises mainly multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which are distinct pathological entities, presenting with a wide phenotypic spectrum. The classic syndromes are now called MSA-Parkinsonism (MSA-P), MSA-cerebellar type (MSA-C), Richardson's syndrome, and corticobasal syndrome. Nonmotor features in AP have been recognized almost since the initial description of these disorders; however, research has been limited. Autonomic dysfunction is the most prominent nonmotor feature of MSA, but also gastrointestinal symptoms, sleep dysfunction, and pain, can be a feature. In PSP and CBD, the most prominent nonmotor symptoms comprise those deriving from the cognitive/neuropsychiatric domain. Apart from assisting the clinician in the differential diagnosis with Parkinson's disease, nonmotor features in AP have a big impact on quality of life and prognosis of AP and their treatment poses a major challenge for clinicians.
Klaus Seppi - One of the best experts on this subject based on the ideXlab platform.
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axial motor clues to identify Atypical Parkinsonism a multicentre european cohort study
Parkinsonism & Related Disorders, 2018Co-Authors: Carlijn D J M Borm, Klaus Seppi, Karen Ostergaard, Florian Krismer, Werner Poewe, Gregor K Wenning, Maria Teresa Pellecchia, Paolo Barone, E L Johnsen, Tanya GurevichAbstract:Abstract Objective Differentiating Parkinson's disease (PD) from Atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it remains unknown which PIGD test – or combination of tests – can best distinguish PD from APD. We evaluated the discriminative value of several widely-used PIGD tests, and aimed to develop a short PIGD evaluation that can discriminate parkinsonian disorders. Methods In this multicentre cohort study patients were recruited by 11 European MSA Study sites. Patients were diagnosed using standardized criteria. Postural instability and gait disability was evaluated using interviews and several clinical tests. Results Nineteen PD, 21 MSA-p and 25 PSP-RS patients were recruited. PIGD was more common in APD compared to PD. There was no significant difference in axial symptoms between PSP-RS and MSA-p, except for self-reported falls (more frequent in PSP-RS patients). The test with the greatest discriminative power to distinguish APD from PD was the ability to perform tandem gait (AUC 0.83; 95% CI 71–94; p Conclusions Our study suggests that simple “bedside” PIGD tests – particularly the combination of tandem gait performance, TUG and retropulsion test – can discriminate APD from PD.
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structural imaging in Atypical Parkinsonism
International Review of Neurobiology, 2018Co-Authors: Beatrice Heim, Florian Krismer, Klaus SeppiAbstract:Abstract Qualitative and quantitative structural magnetic resonance imaging offer objective measures of the underlying neurodegeneration in Atypical Parkinsonism. Regional changes in tissue volume, signal changes and increased deposition of iron as assessed with different structural MRI techniques are surrogate markers of underlying neurodegeneration and may reflect cell loss, microglial proliferation and astroglial activation. Structural MRI has been explored as a tool to enhance diagnostic accuracy in differentiating Atypical parkinsonian disorders (APDs). Moreover, the longitudinal assessment of serial structural MRI-derived parameters offers the opportunity for robust inferences regarding the progression of APDs. This review summarizes recent research findings as (1) a diagnostic tool for APDs as well as (2) as a tool to assess longitudinal changes of serial MRI-derived parameters in the different APDs.
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diagnostic potential of automated subcortical volume segmentation in Atypical Parkinsonism
Neurology, 2016Co-Authors: Christoph Scherfler, Werner Poewe, Gregor K Wenning, Georg Gobel, Christoph Muller, Michael Nocker, Michael Schocke, Klaus SeppiAbstract:Objective: To determine whether automated and observer-independent volumetric MRI analysis is able to discriminate among patients with Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in early to moderately advanced stages of disease. Methods: T1-weighted volumetric MRI from patients with clinically probable PD (n = 40), MSA (n = 40), and PSP (n = 30) and a mean disease duration of 2.8 ± 1.7 y were examined using automated volume measures of 22 subcortical regions. The clinical follow-up period was 2.5 ± 1.2 years. The data were split into a training (n = 72) and a test set (n = 38). The training set was used to build a C4.5 decision tree model in order to classify patients as MSA, PSP, or PD. The classification algorithm was examined by the test set using the final clinical diagnosis at last follow-up as diagnostic gold standard. Results: The midbrain and putaminal volume as well as the cerebellar gray matter compartment were identified as the most significant brain regions to construct a prediction model. The diagnostic accuracy for PD vs MSA or PSP was 97.4%. In contrast, diagnostic accuracy based on validated clinical consensus criteria at the time of MRI acquisition was 62.9%. Conclusions: Volume segmentation of subcortical brain areas differentiates PD from MSA and PSP and improves diagnostic accuracy in patients presenting with early to moderately advanced stage Parkinsonism. Classification of evidence: This study provides Class III evidence that automated MRI analysis accurately discriminates among early-stage PD, MSA, and PSP.
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Update on diffusion MRI in Parkinson's disease and Atypical Parkinsonism.
Journal of the neurological sciences, 2013Co-Authors: Frederick J A Meijer, Bastiaan R. Bloem, Philipp Mahlknecht, Klaus Seppi, Bozena GorajAbstract:Differentiating Parkinson's disease (PD) from other types of neurodegenerative Atypical Parkinsonism (AP) can be challenging, especially in early disease stages. Routine brain magnetic resonance imaging (MRI) can show atrophy or signal changes in several parts of the brain with fairly high specificity for particular forms of AP, but the overall diagnostic value of routine brain MRI is limited. In recent years, various advanced MRI sequences have become available, including diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). Here, we review available literature on the value of diffusion MRI for identifying and quantifying different patterns of neurodegeneration in PD and AP, in relation to what is known of underlying histopathologic changes and clinical presentation of these diseases. Next, we evaluate the value of diffusion MRI to differentiate between PD and AP and the potential value of serial diffusion MRI to monitor disease progression. We conclude that diffusion MRI may quantify patterns of neurodegeneration which could be of additional value in clinical use. Future prospective clinical cohort studies are warranted to assess the added diagnostic value of diffusion MRI.
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freezing of gait in postmortem confirmed Atypical Parkinsonism
Movement Disorders, 2002Co-Authors: Jorg Muller, Klaus Seppi, Nadia Stefanova, Werner Poewe, Irene Litvan, Gregor K WenningAbstract:The frequency and pathophysiology of freezing of gait (FoG) in Atypical Parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed Atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.
Kailash P Bhatia - One of the best experts on this subject based on the ideXlab platform.
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how to approach a patient with Parkinsonism red flags for Atypical Parkinsonism
International Review of Neurobiology, 2019Co-Authors: Eoin Mulroy, Maria Stamelou, Kailash P BhatiaAbstract:Abstract Parkinsonism is a clinical syndrome defined by bradykinesia plus rigidity or tremor. Though most commonly encountered in the setting of idiopathic Parkinson's disease, a number of neurodegenerative, structural, metabolic and toxic neurological disorders can result in Parkinsonism. Accurately diagnosing the underlying cause of Parkinsonism is of both therapeutic and prognostic relevance, especially as we enter the era of disease-modifying treatment trials for neurodegenerative disorders. Being aware of the wide array of potential causes of Parkinsonism is of paramount importance for clinicians. In this chapter, we present a pragmatic clinical approach to patients with Parkinsonism, specifically focusing on ‘red flags’, which should alert one to consider diagnoses other than idiopathic Parkinson's disease.
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Atypical Atypical Parkinsonism critical appraisal of a cohort
Parkinsonism & Related Disorders, 2017Co-Authors: Stephanie T Hirschbichler, Maria Stamelou, Roberto Erro, Christos Ganos, Amit Batla, Bettina Balint, Kailash P BhatiaAbstract:Abstract Background Atypical parkinsonian conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and Dementia with Lewy bodies (DLB) comprise 10–15% of parkinsonian syndromes. Misdiagnosis with Parkinson disease (PD) and within the entities is common, given the absence of reliable biomarkers. However a correct diagnosis is not only important in clinical practice, but also crucial for any trial attempting to identify biomarkers or new treatments. Methods Consecutive patients, who were referred to our tertiary center with a diagnosis of a particular AP were included and the medical records were reviewed retrospectively. We applied each set of current diagnostic research criteria to the respective cohort to see which features fit in and if there are any additional Atypical features “outside” the classic definition. Results Sixty-nine patients were recruited between January 2013 and May 2015 clinically presenting with one of the following phenotypes: 14 MSA, 24 PSP, 19 CBS and 12 DLB. Up to 49% showed additional “Atypical” features and approximately 10% eventually received an alternative diagnosis, in half of whom this being based on genetic testing. Conclusions In a subset of our patients, despite the final diagnosis of an AP being maintained, there were additional “Atypical” features. It remains to be seen if these reflect the clinical heterogeneity of APs, or should prompt a search for an alternative diagnosis. The search for biomarkers is more likely to be successful in homogenous groups of “typical” patients, hence the importance of recognizing “Atypical” features.
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nonmotor features in Atypical Parkinsonism
International Review of Neurobiology, 2017Co-Authors: Kailash P Bhatia, Maria StamelouAbstract:Atypical Parkinsonism (AP) comprises mainly multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which are distinct pathological entities, presenting with a wide phenotypic spectrum. The classic syndromes are now called MSA-Parkinsonism (MSA-P), MSA-cerebellar type (MSA-C), Richardson's syndrome, and corticobasal syndrome. Nonmotor features in AP have been recognized almost since the initial description of these disorders; however, research has been limited. Autonomic dysfunction is the most prominent nonmotor feature of MSA, but also gastrointestinal symptoms, sleep dysfunction, and pain, can be a feature. In PSP and CBD, the most prominent nonmotor symptoms comprise those deriving from the cognitive/neuropsychiatric domain. Apart from assisting the clinician in the differential diagnosis with Parkinson's disease, nonmotor features in AP have a big impact on quality of life and prognosis of AP and their treatment poses a major challenge for clinicians.
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Atypical Parkinsonism - new advances.
Current Opinion in Neurology, 2016Co-Authors: Maria Stamelou, Kailash P BhatiaAbstract:PURPOSE OF REVIEW This update discusses novel aspects on genetics, pathophysiology and therapeutic approaches for Atypical Parkinsonism (progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy) published in the last 2 years. RECENT FINDINGS In terms of genetics, in progressive supranuclear palsy and corticobasal degeneration new risk loci have been identified but also their possible association to disease pathogenesis. In multiple system atrophy, there is still a debate as to whether COQ2 variants are associated with disease, at least in non-Asian population, whereas at the same time evidence of coenzyme Q10 deficiency in serum and brains of MSA patients has been reported. In terms of pathogenesis, the 'prion' hypothesis has prevailed in the last years in the literature, and the first clinical studies based on such disease mechanisms are already in phase I. Despite all these discoveries, clinical diagnosis still remains poor, and phenotypic variability is reported much higher than previously thought. A plethora of studies testing possible neuroprotective agents are currently ongoing. SUMMARY The knowledge on all aspects of Atypical Parkinsonism has increased tremendously in the last 2 years, leading the field closer to the understanding of the pathophysiology of these diseases, and to the discovery of a neuroprotective treatment.
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Atypical Parkinsonism diagnosis and treatment
Neurologic Clinics, 2015Co-Authors: Maria Stamelou, Kailash P BhatiaAbstract:Atypical Parkinsonism comprises typically progressive supranuclear palsy, corticobasal degeneration, and mutilple system atrophy, which are distinct pathologic entities; despite ongoing research, their cause and pathophysiology are still unknown, and there are no biomarkers or effective treatments available. The expanding phenotypic spectrum of these disorders as well as the expanding pathologic spectrum of their classic phenotypes makes the early differential diagnosis challenging for the clinician. Here, clinical features and investigations that may help to diagnose these conditions and the existing limited treatment options are discussed.
Bastiaan R. Bloem - One of the best experts on this subject based on the ideXlab platform.
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nigrosome 1 on susceptibility weighted imaging to differentiate parkinson s disease from Atypical Parkinsonism an in vivo and ex vivo pilot study
Polish Journal of Radiology, 2016Co-Authors: Frederick J A Meijer, Bastiaan R. Bloem, Marcel M Verbeek, Rianne A J Esselink, Stefan C A Steens, Anouke Van Rumund, Annemarie Van Cappellen Van Walsum, Benno Kusters, Bozena GorajAbstract:BACKGROUND: Previous case-control studies have suggested that the absence of a swallow-tail appearance in the substantia nigra on high-resolution SWI, representing nigrosome-1, has high accuracy to identify Parkinson's disease (PD). The first goal of our study was to evaluate nigrosome-1 ex vivo using optimized high-resolution susceptibility sensitive MRI. Our second goal was to evaluate its diagnostic value in vivo using a clinical 3T SWI sequence to differentiate between PD and Atypical Parkinsonism (AP) in a cohort of patients with early-stage Parkinsonism. MATERIAL/METHODS: Case-control pilot study to evaluate nigrosome-1 ex vivo (2 PD, 2 controls), using high-resolution susceptibility sensitive sequences at 11.7 T MRI. Next, evaluation of nigrosome-1 in vivo using a clinical 3 T SWI sequence in a prospective cohort of 60 patients with early-stage Parkinsonism (39 PD, 21 AP). Moreover, 12 control subjects were scanned. The bilateral substantia nigra was evaluated by two neuroradiologists for the presence, absence or indecisive presence of nigrosome-1. The discriminative power was evaluated by Receiver-Operating Characteristic. RESULTS: We identified nigrosome-1 in ex vivo control subjects. Nigrosome-1 was not identified in the ex vivo PD cases. In our prospective clinical cohort study, the AUC for the swallow-tail sign to discriminate between PD and AP was 0.56 (0.41-0.71) for reader 1 and 0.68 (0.55-0.82) for reader 2. CONCLUSIONS: The diagnostic accuracy of the swallow-tail sign was marginal to discriminate between PD and AP using our clinical 3 T SWI sequence.
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Diagnostic accuracy of Parkinson's disease and Atypical Parkinsonism in nursing homes
Parkinsonism & Related Disorders, 2014Co-Authors: N.j. Weerkamp, Sytse U. Zuidema, Raymond T.c.m. Koopmans, Gerrit Tissingh, Marten Munneke, Patrick J P Poels, Bastiaan R. BloemAbstract:INTRODUCTION: Management of Parkinson's disease (PD) and Atypical Parkinsonism in nursing homes depends on a timely and accurate diagnosis. However, little is known about the diagnostic accuracy of these parkinsonian syndromes in nursing homes. We examined this issue in a large group of Dutch nursing home residents. METHODS: Twelve large nursing home organizations in the Netherlands accounting for 100 nursing homes with a total population of 5480 residents participated. Residents with PD or Atypical Parkinsonism were identified according to their nursing home medical chart diagnosis. Additionally, local pharmacists provided a list of all residents using antiparkinson medication. We compared the admission diagnosis to a clinical diagnosis made in the study, based upon interview and detailed neurological examination by movement disorders experts. Diagnoses were based on accepted clinical criteria for PD and Atypical Parkinsonism. RESULTS: In the total population of 5480 residents, 258 had previously been diagnosed with a form of Parkinsonism according to their medical record. In 53 of these residents (20.5%) we changed or rejected the diagnosis. Specifically, we found no Parkinsonism in 22 of these 53 residents (8.5% of all patients with suspected Parkinsonism). In the remaining 31 residents (12%), we established a new diagnosis within the parkinsonian spectrum. CONCLUSIONS: In a large population of Dutch nursing home residents, 20% of diagnoses within the parkinsonian spectrum were inaccurate. Almost 9% of residents had inadvertently received a diagnosis of Parkinsonism. Better recognition of Parkinsonism in nursing homes is important, because of the consequences for management and prognosis.
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medio lateral balance impairment differentiates between parkinson s disease and Atypical Parkinsonism
Journal of Parkinson's disease, 2014Co-Authors: Jorik Nonnekes, Wilson F Abdo, Marjolein B Aerts, Bastiaan R. BloemAbstract:In early disease stages, it can be difficult to differentiate clinically between Parkinson's disease and the various forms of Atypical Parkinsonism, like multiple system atrophy or progressive supranuclear palsy. Balance impairment in the medio-lateral plane (i.e. sideways) is often seen in patients with a form of Atypical Parkinsonism, but not in patients with Parkinson's disease. This is reflected by the distance between the feet during gait, which is typically normal (or even narrow) in Parkinson's disease, but widened in Atypical Parkinsonism. Estimating this stance width depends on subjective judgement, and is difficult to quantify in clinical practice. Here, we emphasize that this medio-lateral balance impairment can also be revealed using two simple tests: (1) inability to perform tandem gait (taking one or more side steps being abnormal); and (2) self-report by patients who have lost the ability to ride a bicycle. Both tests have a good diagnostic yield in differentiating between Parkinson's disease and Atypical Parkinsonism, even early in the course of the disease.
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Update on diffusion MRI in Parkinson's disease and Atypical Parkinsonism.
Journal of the neurological sciences, 2013Co-Authors: Frederick J A Meijer, Bastiaan R. Bloem, Philipp Mahlknecht, Klaus Seppi, Bozena GorajAbstract:Differentiating Parkinson's disease (PD) from other types of neurodegenerative Atypical Parkinsonism (AP) can be challenging, especially in early disease stages. Routine brain magnetic resonance imaging (MRI) can show atrophy or signal changes in several parts of the brain with fairly high specificity for particular forms of AP, but the overall diagnostic value of routine brain MRI is limited. In recent years, various advanced MRI sequences have become available, including diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). Here, we review available literature on the value of diffusion MRI for identifying and quantifying different patterns of neurodegeneration in PD and AP, in relation to what is known of underlying histopathologic changes and clinical presentation of these diseases. Next, we evaluate the value of diffusion MRI to differentiate between PD and AP and the potential value of serial diffusion MRI to monitor disease progression. We conclude that diffusion MRI may quantify patterns of neurodegeneration which could be of additional value in clinical use. Future prospective clinical cohort studies are warranted to assess the added diagnostic value of diffusion MRI.
Annie Lannuzel - One of the best experts on this subject based on the ideXlab platform.
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further evidence for a distinctive Atypical degenerative Parkinsonism in the caribbean a new cluster in the french west indian island of martinique
Journal of the Neurological Sciences, 2018Co-Authors: Annie Lannuzel, Regine Edragas, Angela Lackmy, Benoit Tressieres, Veronique Pelonde, Mireille Edimonana Kaptue, Sylvie Mecharles, Alexis Demas, Billy FrancoisAbstract:Abstract Background A high prevalence of an Atypical levodopa-resistant Parkinsonism has been reported in the Caribbean island of Guadeloupe. These seminal observations have not been replicated or extended to neighbouring populations who share genetic and environmental characteristics. Methods To further characterise this Atypical Parkinsonism we prospectively investigated 305 consecutive patients with neurodegenerative Parkinsonism in a community-based population from Guadeloupe and Martinique, a neighbouring French Caribbean island where the population has similar environmental and genetic backgrounds. The aims of this study were to confirm the frequency of Atypical Parkinsonism within this cohort and to precisely define its clinical phenotype. Results A high frequency (66%) of Atypical Parkinsonism was identified in both Guadeloupe and Martinique. The clinical phenotype consisted of a levodopa-resistant Parkinsonism with postural instability (72%), early dementia (58%), dysautonomia (58%), rapid-eye-movement sleep behavioural disorder (53%), hallucinations (43%), and supranuclear gaze palsy (29%). A low educational level was identified as a major risk factor for developing Atypical Parkinsonism (p Conclusion Our findings support the existence of a distinctive Atypical Parkinsonism – Caribbean Parkinsonism – within the French Caribbean Islands. This could either correspond to a single entity or reflect a propensity for developing more widespread and rapidly progressive lesions in Caribbean patients with Parkinsonism. In both cases, genetic susceptibility and/or environmental exposure may be involved.
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the psp associated mapt h1 subhaplotype in guadeloupean Atypical Parkinsonism
Movement Disorders, 2008Co-Authors: Agnes Camuzat, Merle Ruberg, Marc Romana, Alexandra Durr, J Feingold, Alexis Brice, Annie LannuzelAbstract:The aim of this study was to determine whether the H1 subhaplotype in MAPT associated with progressive supranuclear palsy (PSP) in Caucasians confers risk for PSP-like Atypical Parkinsonism in Guadeloupe, a tauopathy. Guadeloupean controls and patients with Atypical and idiopathic Parkinsonism and ethnically and age-matched controls were genotyped for H1 and H2 alleles, then for the H1 subhaplotype associated with PSP in Caucasians, using previously described haplotype-tagging single nucleotide polymorphisms (Ht-SNPs) in linkage disequilibrium at the MAPT locus. Most Guadeloupean controls and patients were homozygous for the H1 allele; only 5% were heterozygous for the H2 allele, consistent with the European contribution to the racial admixture in Guadeloupe, but equivalent to the frequency found in Caucasian PSP patients. The frequencies of the Ht-SNPs used to determine the PSP-associated H1 subhaplotype in both Guadeloupean controls and parkinsonians were similar, indicating that the H1 subhaplotype associated with PSP in Caucasians was not a risk factor for PSP-like Atypical Parkinsonism in Guadeloupe. Interestingly, they were also similar to the frequencies in Caucasian PSP patients. The major H1 subhaplotype in Guadeloupe, determined by analysis of linkage desequibrium, differed from the major Caucasian subhaplotype, but corresponded to minor alleles previously described. © 2008 Movement Disorder Society
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Atypical Parkinsonism in guadeloupe a common risk factor for two closely related phenotypes
Brain, 2007Co-Authors: Annie Lannuzel, Gunter U Hoglinger, Etienne C Hirsch, Sofie Verhaeghe, L Gire, S Belson, M Escobarkhondiker, P Poullain, Wolfgang H Oertel, Bruno DuboisAbstract:In Guadeloupe, there is an abnormally high frequency of Atypical Parkinsonism. Only one-third of the patients that develop parkinsonian symptoms were reported to present the classical features of idiopathic Parkinson disease and one-third a syndrome resembling progressive supranuclear palsy (PSP). The others were unclassifiable, according to established criteria. We carried out a cross-sectional study of 160 parkinsonian patients to: (i) define more precisely the clinical phenotypes of the PSP-like syndrome and the Parkinsonism that was considered unclassifiable in comparison with previously known disorders; (ii) define the neuropsychological and brain imaging features of these patients; (iii) evaluate to what extent a candidate aetiological factor, the mitochondrial complex I inhibitor annonacin contained in the fruit and leaves of the tropical plant Annona muricata (soursop) plays a role in the neurological syndrome. Neuropsychological tests and MRI were used to classify the patients into those with Parkinson’s disease (31%), Guadeloupean PSP-like syndrome (32%), Guadeloupean Parkinsonism^dementia complex (PDC, 31%) and other Parkinsonism-related disorders (6%). Patients with a PSP-like syndrome developed levodopa-resistant Parkinsonism, associated with early postural instability and supranuclear oculomotor dysfunction. They differed, however, from classical PSP patients by the frequency of tremor (450%), dysautonomia (50%) and the occurrence of hallucinations (59%). PDC patients had levodopa-resistant Parkinsonism associated with frontosubcortical dementia, 52% of these patients had hallucinations, but, importantly, none had oculomotor dysfunction. The pattern of neuropsychological deficits was similar in both subgroups. Cerebral atrophy was seen in the majority of the PSP-like and PDC patients, with enlargement of the third ventricle and marked T2-hypointensity in the basal ganglia, particularly the substantia nigra. Consumption of soursop was significantly greater in both PSP-like and PDC patients than in controls and Parkinson’s disease patients. In conclusion, Atypical Guadeloupean Parkinsonism comprises two forms of Parkinsonism and dementia that differ clinically by the presence of oculomotor signs, but have similar cognitive profiles and neuroimaging features, suggesting that they may constitute a single disease entity, and both were similarly exposed to annonaceous neurotoxins, notably annonacin.
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is Atypical Parkinsonism in the caribbean caused by the consumption of annonacae
Journal of Neural Transmission-supplement, 2006Co-Authors: Annie Lannuzel, Pierre Champy, Gunter U Hoglinger, Patrick P Michel, Etienne C Hirsch, Merle RubergAbstract:An abnormally frequent Atypical levodopa-unresponsive, akinetic-rigid syndrome with some similarity to PSP was identified in the Caribbean island Guadeloupe, and was associated with the consumption of plants of the Annonacea family, especially Annona muricata (corossol, soursop) suggesting a possible toxic etiology. Annonaceae contain two groups of potential toxins, alkaloids and acetogenins. Both alkaloids and annonacin, the most abundant acetogenin, were toxic in vitro to dopaminergic and other neurons. However we have focused our work on annonacin for two reasons: (1) annonacin was toxic in nanomolar concentrations, whereas micromolar concentrations of the alkaloids were needed, (2) acetogenins are potent mitochondrial poisons, like other Parkinsonism-inducing compounds. We have also shown that high concentrations of annonacin are present in the fruit or aqueous extracts of the leaves of A. muricata, can cross the blood brain barrier since it was detected in brain parenchyma of rats treated chronically with the molecule, and induced neurodegeneration of basal ganglia in these animals, similar to that observed in Atypical Parkinsonism. These studies reinforce the concept that consumption of Annonaceae may contribute to the pathogenesis of Atypical Parkinsonism in Guadeloupe.
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quantification of acetogenins in annona muricata linked to Atypical Parkinsonism in guadeloupe
Movement Disorders, 2005Co-Authors: Pierre Champy, Christophe Gleye, Olivier Laprévote, Djibril Fall, Alice Melot, Gunter U Hoglinger, Merle Ruberg, Annie Lannuzel, Alain LaurensAbstract:Atypical Parkinsonism in Guadeloupe has been as- sociated with the consumption of fruit and infusions or decoc- tions prepared from leaves of Annona muricata L. (Annon- aceae), which contains annonaceous acetogenins, lipophilic inhibitors of complex I of the mitochondrial respiratory chain. We have determined the concentrations of annonacin, the major acetogenin in A. muricata, in extracts of fruit and leaves by matrix-assisted laser desorption-ionization mass spectrom- etry. An average fruit is estimated to contain about 15 mg of annonacin, a can of commercial nectar 36 mg, and a cup of infusion or decoction 140 g. As an indication of its potential toxicity, an adult who consumes one fruit or can of nectar a day is estimated to ingest over 1 year the amount of annonacin that induced brain lesions in rats receiving purified annonacin by intravenous infusion. © 2005 Movement Disorder Society
