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1.
Clin Auton Res ; 34(2): 253-268, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38630378

RESUMO

PURPOSE: To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort. METHODS: The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis. RESULTS: The literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004). CONCLUSION: The available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.


Assuntos
Atrofia de Múltiplos Sistemas , Caracteres Sexuais , Humanos , Atrofia de Múltiplos Sistemas/fisiopatologia , Atrofia de Múltiplos Sistemas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Estudos de Coortes
2.
Clin Auton Res ; 32(2): 103-114, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35149937

RESUMO

PURPOSE: The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy. METHODS: A prospective study including 19 Parkinson's disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests. RESULTS: Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson's disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson's disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson's disease patients (p < 0.001). CONCLUSIONS: The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson's disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson's disease patients.


Assuntos
Iodo , Atrofia de Múltiplos Sistemas , Doença de Parkinson , 3-Iodobenzilguanidina , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Estudos Prospectivos
3.
Mov Disord ; 35(12): 2333-2338, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32881058

RESUMO

BACKGROUND: Multiple system atrophy (MSA) and Parkinson's disease (PD) patients develop respiratory and cardiovascular disturbances including obstructive sleep apnea, orthostatic hypotension, and nocturnal stridor. We hypothesized that, associated with these respiratory and cardiovascular disturbances, hypoxic events may occur in MSA and PD brains that may play a role in disease progression. The objective of this study was to evaluate the presence of hypoxia in nonneurological controls and PD and MSA patients. METHODS: Molecular levels of hypoxia markers were measured in postmortem brain tissue from controls and PD and MSA cases. RESULTS: MSA brain showed signs of chronic hypoxia characterized by the significant accumulation of the hypoxic marker HIF2α as compared to PD patients and controls. We detected no differences between MSA subtypes. Signs of hypoxia were also observed in PD patients with a clinical presentation similar to the MSA cases. CONCLUSIONS: The results obtained from this study suggest a new alternative pathway associated with α-synucleinopathies that may contribute to the pathogenesis of these disorders. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Hipotensão Ortostática , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Sinucleinopatias , Humanos , Hipóxia , Doença de Parkinson/complicações
4.
J Neural Transm (Vienna) ; 125(2): 273-274, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29185076

RESUMO

Unfortunately, Author has now noticed two mistakes in Fig. 1. Author has written "peripher" instead of "peripheral" and "Secundary" instead of "Secondary".

6.
J Neural Transm (Vienna) ; 124(12): 1567-1605, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29058089

RESUMO

Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced hypotension are common features of cardiovascular autonomic failure. Despite the serious impact on patient's quality of life, evidence-based guidelines for non-pharmacological and pharmacological management are lacking at present. Here, we provide a systematic review of the literature on therapeutic options for neurogenic orthostatic hypotension and related symptoms with evidence-based recommendations according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Patient's education and non-pharmacological measures remain essential, with strong recommendation for use of abdominal binders. Based on quality of evidence and safety issues, midodrine and droxidopa reach a strong recommendation level for pharmacological treatment of neurogenic orthostatic hypotension. In selected cases, a range of alternative agents can be considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation strength is weak and quality of evidence is low (atomoxetine, octreotide) or very low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids, ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine, methylphenidate and desmopressin). In case of severe postprandial hypotension, acarbose and octreotide are recommended (strong recommendation, moderate level of evidence). Alternatively, voglibose or caffeine, for which a weak recommendation is available, may be useful.


Assuntos
Medicina Baseada em Evidências , Hipotensão Ortostática/terapia , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino
7.
Mov Disord Clin Pract ; 11(7): 855-860, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38715209

RESUMO

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) reduces antiparkinsonian medications in Parkinson's disease (PD) compared with the preoperative state. Longitudinal and comparative studies on this effect are lacking. OBJECTIVE: To compare longitudinal trajectories of antiparkinsonian medication in STN-DBS treated patients to non-surgically treated control patients. METHODS: We collected retrospective information on antiparkinsonian medication from PD patients that underwent subthalamic DBS between 1999 and 2010 and control PD patients similar in age at onset and baseline, sex-distribution, and comorbidities. RESULTS: In 74 DBS patients levodopa-equivalent daily dose (LEDD) were reduced by 33.9-56.0% in relation to the preoperative baseline over the 14-year observational period. In 61 control patients LEDDs increased over approximately 10 years, causing a significant divergence between groups. The largest difference amongst single drug-classes was observed for dopamine agonists. CONCLUSION: In PD patients, chronic STN-DBS was associated with a lower LEDD compared with control patients over 14 years.


Assuntos
Antiparkinsonianos , Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/tratamento farmacológico , Estimulação Encefálica Profunda/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/administração & dosagem , Idoso , Estudos Retrospectivos , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Estudos Longitudinais , Resultado do Tratamento
8.
J Clin Sleep Med ; 19(1): 63-71, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36004744

RESUMO

STUDY OBJECTIVES: Sleep disorders, daytime sleepiness, and autonomic dysfunction are commonly reported among patients with multiple system atrophy and Parkinson disease (PD). We aimed to assess sleep and autonomic function in these patients to evaluate the relationships between sleep disorders, excessive daytime sleepiness, and autonomic function. METHODS: Twenty patients with multiple system atrophy (n = 7) and PD (n = 13) underwent clinical assessment including questionnaires for autonomic function and sleep. Cardiovascular autonomic function tests and 2-night video-polysomnography were followed by administration of the Multiple Sleep Latency Test. Rapid eye movement sleep without atonia was quantified in the chin, flexor digitorum superficialis, tibial anterior, and sternocleidomastoid muscles. RESULTS: Rapid eye movement sleep behavior disorder was associated with orthostatic hypotension (P = .017) and constipation (P = .019) in PD. Patients with orthostatic hypotension had higher rapid eye movement sleep without atonia indices than those without orthostatic hypotension (P < .001). The Sleep Innsbruck Barcelona rapid eye movement sleep without atonia index ("any" chin and/or flexor digitorum superficialis) correlated with systolic/diastolic blood pressure fall upon tilt-table examination in patients with multiple system atrophy (P < .05) and with gastrointestinal (P = .010), urinary (P = .022), and total Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction scores (P = .006) in all patients. Patients with a pathological deep breathing ratio showed higher Sleep Innsbruck Barcelona indices (P = .031). Objective daytime sleepiness was exclusively present in PD (P = .034) and correlated with levodopa-equivalent dosage (P = .031). CONCLUSIONS: The relationship of autonomic dysfunction with rapid eye movement sleep without atonia in PD and multiple system atrophy is accounted for by shared brainstem neuropathology and likely identifies patients in a more advanced stage of disease. Excessive daytime sleepiness is found exclusively in PD and may be secondary to levodopa treatment and not related to α-synuclein disease. CITATION: Eckhardt C, Fanciulli A, Högl B, et al. Analysis of sleep, daytime sleepiness, and autonomic function and multiple system atrophy and Parkinson disease: a prospective study. J Clin Sleep Med. 2023;19(1):63-71.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Hipotensão Ortostática , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Doença de Parkinson/complicações , Atrofia de Múltiplos Sistemas/complicações , Estudos Prospectivos , Levodopa/uso terapêutico , Hipotensão Ortostática/complicações , Hipotensão Ortostática/diagnóstico , Sono , Distúrbios do Sono por Sonolência Excessiva/complicações , Transtorno do Comportamento do Sono REM/diagnóstico
9.
Mov Disord Clin Pract ; 8(7): 1052-1060, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34631941

RESUMO

BACKGROUND: Urological dysfunction in patients with multiple system atrophy (MSA) is one of the main manifestations of autonomic failure. Urodynamic examination is clinically relevant since underlying pathophysiology of lower urinary tract (LUT) dysfunction can be variable. OBJECTIVE: Evaluation of the pathophysiology of urological symptoms and exploration of differences in urodynamic patterns of LUT dysfunction between MSA-P and MSA-C. METHODS: Retrospective study of patients with possible and probable MSA who were referred for urodynamic studies between 2004 and 2019. Demographic data, medical history, physical examination and urodynamic studies assessing storage and voiding dysfunction were obtained. RESULTS: Seventy-four patients were included in this study (MSA-P 64.9% n = 48; median age 62.5 (IQR 56.8-70) years). Detrusor overactivity during filling phase was noted in 58.1% (n = 43) of the patients. In the voiding phase, detrusor sphincter dyssynergia and detrusor underactivity were observed in 24.6% (n = 17) and in 62.1% (n = 41) of the patients, respectively. A postmicturition residual volume of over 100 ml was present in 71.4% (n = 50) of the patients. Comparison of MSA subtypes showed weaker detrusor contractility in MSA-P compared to MSA-C [pdetQmax 26.2 vs. 34.4 cmH20, P = 0.04]. In 56.2% (n = 41) of patients pathophysiology of LUT dysfunction was deemed to be neurogenic and consistent with the diagnosis of MSA. In 35.6% (n = 26) urodynamic pattern suggested other urological co-morbidities. CONCLUSION: Urodynamic evaluation is an important tool to analyze the pattern of LUT dysfunction in MSA. Impaired detrusor contractility was seen more in MSA-P which needs to be investigated in further studies.

10.
Ann Clin Transl Neurol ; 7(2): 219-228, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32031752

RESUMO

OBJECTIVE: Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between-group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition. METHODS: This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work-up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD-plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS-D). RESULTS: The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P < 0.05) in a screening of executive functions (FAB) and in phonemic verbal fluency. Depression and anxiety scores were elevated in 28% and 22% of MSA patients, respectively. Cognitive profile, depression, and anxiety levels were comparable between patients with and without OH. INTERPRETATION: Cognitive deficits are relatively frequent in MSA and primarily affect executive functions and verbal memory. Future comparative studies including Parkinson dementia, Lewy body disease, and MSA cases with and without OH are required to elucidate disease-specific cognitive profiles in these synucleinopathies and to examine the influence of cardiovascular autonomic dysfunction on cognitive function in MSA.


Assuntos
Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Hipotensão Ortostática/fisiopatologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Idoso , Ansiedade/fisiopatologia , Disfunção Cognitiva/etiologia , Depressão/fisiopatologia , Feminino , Humanos , Hipotensão Ortostática/etiologia , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/complicações , Testes Neuropsicológicos , Estudos Retrospectivos
11.
Mov Disord Clin Pract ; 7(7): 782-787, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33033735

RESUMO

BACKGROUND: The long-term impact of deep brain stimulation (DBS) on Parkinson's disease (PD) is difficult to assess and has not yet been rigorously evaluated in comparison to its natural history. OBJECTIVE: Comparison of key disability milestones (recurrent falls, psychosis, dementia, and institutionalization) and death in patients with PD with versus without DBS. METHODS: We collected retrospective information from clinical notes of patients with PD at our center that were implanted with subthalamic DBS >8 years ago (1999-2010) and a control group of PD patients without DBS similar in age at onset, age at baseline, sex distribution, and number of comorbidities at baseline (extracted from a registry study performed in 2004). Cox regression models were used to calculate hazard ratios, adjusted for potential baseline confounding variables (age, sex, disease duration, disease severity, and number of comorbidities). RESULTS: A total of 74 DBS-treated and 61 control patients with PD were included. For a median observational period of 14 years, patients treated with DBS were at lower risk of experiencing recurrent falls (hazard ratio = 0.57; 95% confidence interval, 0.37-0.90; P = 0.015) and psychosis (hazard ratio = 0.26; 95% confidence interval, 0.12-0.59; P = 0.001) compared with control patients. There was no significant difference in risk for dementia, institutionalization, or death. Disease progression as assessed by Hoehn and Yahr scores was not slower in DBS-treated patients. CONCLUSIONS: Treatment with chronic subthalamic DBS was associated with lower risk for recurrent falls and psychotic symptoms, effects that may be mediated through improved motor symptom control and reduction in dopaminergic therapies, respectively. There was no evidence for DBS effects on underlying disease progression.

12.
J Alzheimers Dis ; 61(4): 1253-1273, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29376857

RESUMO

Iron is essential for cellular development and maintenance of multiple physiological processes in the central nervous system. The disturbance of its homeostasis leads to abnormal iron deposition in the brain and causes neurotoxicity via generation of free radicals and oxidative stress. Iron toxicity has been established in the pathogenesis of Parkinson's disease; however, its contribution to multiple system atrophy (MSA) remains elusive. MSA is characterized by cytoplasmic inclusions of misfolded α-synuclein (α-SYN) in oligodendrocytes referred to as glial cytoplasmic inclusions (GCIs). Remarkably, the oligodendrocytes possess high amounts of iron, which together with GCI pathology make a contribution toward MSA pathogenesis likely. Consistent with this observation, the GCI density is associated with neurodegeneration in central autonomic networks as well as olivopontocerebellar and striatonigral pathways. Iron converts native α-SYN into a ß-sheet conformation and promotes its aggregation either directly or via increasing levels of oxidative stress. Interestingly, α-SYN possesses ferrireductase activity and α-SYN expression underlies iron mediated translational control via RNA stem loop structures. Despite a correlation between progressive putaminal atrophy and iron accumulation as well as clinical decline, it remains unclear whether pathologic iron accumulation in MSA is a secondary event in the cascade of neuronal degeneration rather than a primary cause. This review summarizes the current knowledge of iron in MSA and gives evidence for perturbed iron homeostasis as a potential pathogenic factor in MSA-associated neurodegeneration.


Assuntos
Encéfalo/patologia , Ferro/fisiologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Humanos , Corpos de Inclusão/fisiologia , Imageamento por Ressonância Magnética , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Oligodendroglia/fisiologia , Transtornos Parkinsonianos/diagnóstico por imagem , alfa-Sinucleína/fisiologia
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