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1.
Jinhua Zheng Xinglong Yang Yalan Chen Quanzhen Zhao Sijia Tian Hongyan Huang Yanming Xu 《Clinical autonomic research》2017,27(2):103-106
Purpose
To compare the order of presentation of bladder and motor symptoms between multiple system atrophy phenotypes.Methods
Medical records were retrospectively reviewed in 144 patients.Results
Bladder symptoms occurred either before or within 12 months after onset of motor symptoms in significantly more patients with the cerebellar phenotype than the parkinsonian phenotype (80 vs. 53%, p = 0.003); similar results were observed for urinary incontinence (79 vs. 45%, p = 0.001).Conclusions
Urinary dysfunction is more likely to appear either before or shortly after motor symptoms in the cerebellar phenotype than in the parkinsonian phenotype.2.
Jin-Sung Park Ryan L. Davis Carolyn M. Sue 《Current neurology and neuroscience reports》2018,18(5):21
Purpose of Review
Parkinson’s disease (PD) is a complex neurodegenerative disorder, the aetiology of which is still largely unknown. Overwhelming evidence indicates that mitochondrial dysfunction is a central factor in PD pathophysiology. Here we review recent developments around mitochondrial dysfunction in familial and sporadic PD, with a brief overview of emerging therapies targeting mitochondrial dysfunction.Recent Findings
Increasing evidence supports the critical role for mitochondrial dysfunction in the development of sporadic PD, while the involvement of familial PD-related genes in the regulation of mitochondrial biology has been expanded by the discovery of new mitochondria-associated disease loci and the identification of their novel functions.Summary
Recent research has expanded knowledge on the mechanistic details underlying mitochondrial dysfunction in PD, with the discovery of new therapeutic targets providing invaluable insights into the essential role of mitochondria in PD pathogenesis and unique opportunities for drug development.3.
Purpose of Review
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Sleep dysfunction is one of the most common non-motor manifestations of PD that has gained significant interest over the past two decades due to its impact on the daily lives of PD patients, poorly understood mechanisms, and limited treatment options. In this review, we discuss the most common sleep disorders in PD and present recent investigations that have broadened our understanding of the epidemiology, clinical manifestations, diagnosis, and treatment of disturbed sleep and alertness in PD.Resent Findings
The etiology of impaired sleep-wake cycles in PD is multifactorial. Sleep dysfunction in PD encompasses insomnia, REM sleep behavior disorder, sleep-disordered breathing, restless legs syndrome, and circadian dysregulation. Despite the high prevalence of sleep dysfunction in PD, evidence supporting the efficacy of treatment strategies is limited.Summary
We are at the opportune time to advance our understanding of sleep dysfunction in PD, which will hopefully lead to mechanisms-driven interventions for better sleep and allow us to approach sleep as a modifiable therapeutic target for other non-motor and motor manifestations in PD.4.
Risa Isonaka Patti Sullivan Yunden Jinsmaa Abraham Corrales David S. Goldstein 《Clinical autonomic research》2018,28(2):223-230
Objective
Lewy body forms of primary chronic autonomic failure (CAF) such as incidental Lewy body disease (ILBD), Parkinson’s disease (PD), and pure autonomic failure evolving into dementia with Lewy bodies (PAF+DLB) feature cardiac sympathetic denervation, whereas multiple system atrophy (MSA) in most cases does not. What links Lewy bodies with cardiac sympathetic denervation in CAF? In familial PD, abnormalities of the alpha-synuclein (AS) gene cause CAF and cardiac sympathetic denervation; and in sporadic PD, brainstem Lewy bodies contain AS co-localized with tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Cytotoxicity from AS deposition within sympathetic neurons might explain noradrenergic denervation in Lewy body forms of CAF. We used immunofluorescence microscopy (IM) to explore this possibility in sympathetic ganglia obtained at autopsy from CAF patients.Methods
Immunoreactive AS and TH were imaged in sympathetic ganglion tissue from 6 control subjects (2 with ILBD), 5 PD patients (1 with concurrent PSP), and 3 patients with CAF (2 PAF + DLB, 1 MSA).Results
MSA involved normal ganglionic TH and no AS deposition. In ILBD TH was variably decreased, and TH and AS were co-localized in Lewy bodies. In PD TH was substantially decreased, and TH and AS were co-localized in Lewy bodies. In PAF + DLB TH was virtually absent, but AS was present in Lewy bodies. The PD + PSP patient had AS co-localized with tau but not TH.Conclusions
Sympathetic denervation and intraneuronal AS deposition are correlated across CAF syndromes, consistent with a pathogenic contribution of synucleinopathy to cardiac noradrenergic deficiency in Lewy body diseases.5.
Ezidin G. Kaddumi 《Clinical autonomic research》2016,26(1):33-39
Purpose
Many studies have demonstrated the convergence of vagal inputs into brainstem centers with inputs from the urinary bladder and colon, as well as the convergence of vagal inputs into other centers controlling the urinary bladder and colon reflexes. However, the effect of the vagal inputs on the interaction between the urinary bladder and other pelvic organs has not been studied. In this study, the effect of bilateral cervical vagotomy on the distal colon to urinary bladder reflex was examined.Methods
Changes to cystometry parameters in response to increased distal colon distensions (1, 2, and 3 ml) were tested in urethane-anesthetized male rats with or without bilateral cervical vagotomy.Results
In animals with intact vagus nerves, 1 and 2 ml distal colon distentions had no significant effects on micturition frequency; however, 3 ml distal colon distention significantly decreased the frequency of micturition cycles. Also, 3 ml distal colon distention inhibited micturition cycles in 37.5 % of these animals. On the other hand, following cervical vagotomy, 1 ml distal colon distention was enough to significantly decrease the frequency of micturition cycles and to inhibit the cycles in 75 % of the animals.Conclusion
These results demonstrate the presence of supraspinal inhibitory regulation, via the vagus nerve, over the distal colon to urinary bladder inhibitory reflex.6.
Enrica Olivola Livia Brusa Camilla Rocchi Orazio Schillaci Claudio Liguori Rocco Cerroni Mariangela Pierantozzi Agostino Chiaravalloti Alessandro Stefani Fabrizio Stocchi 《Neurological sciences》2018,39(12):2169-2174
Background
Despite its negative impact on quality of life, fatigue in Parkinson’s disease (PD) remains an under-recognized issue and the underlying pathology is undetermined.Objective
To contribute at understanding the pathogenesis of fatigue in a naturalistic cohort of cognitively intact PD patients.Methods
In a Caucasian population of PD patients (n?=?27), we evaluated to what extent fatigue (quantified as PFS-16 score) is associated with PD duration and with autonomic dysfunction, studied by both MIBG scintigraphy and autonomic nervous system testing. The latter included the head-up tilt test, Valsalva maneuver, deep breathing, and handgrip tests.Results
PFS-16 score correlated with disease duration (R?=?0.57, p?=?0.002). Fatigue showed a clear correlation with deep breathing test (R?=???0.53, p?=?0.004) but not with the MIBG H/M ratios.Conclusions
Our data are consistent with a multifactorial pathogenesis of fatigue and with effects of dopamine depletion in PD-related fatigue; on the other hand, our findings do not support a role for sympathetic denervation in PD-related fatigue.7.
Purpose of Review
Multiple sclerosis (MS) is the most frequent neuroinflammatory disease of the central nervous system and is commonly associated with lower urinary tract (LUT) dysfunction. As a consequence, health-related quality of life is often impaired and the upper urinary tract might be at risk for damage. The aim of this review is to give an overview of current treatment options for LUT dysfunction in patients with MS.Recent Findings
The treatment is tailored to the type of dysfunction—storage or voiding dysfunction—beginning with conservative treatment options and ending with invasive therapies and surgery. Additionally, alternative options, e.g., different intravesical therapies or cannabinoids, have been evaluated in recent years with promising results.Summary
Current available therapies offer different possible treatments for LUT dysfunction in patients with MS. They address either voiding or storage dysfunction and therefore ameliorate LUT symptoms improve quality of life and protect the upper urinary tract.8.
Alessandra Fanciulli Georg Göbel Jean Pierre Ndayisaba Roberta Granata Susanne Duerr Stefano Strano Carlo Colosimo Werner Poewe Francesco E. Pontieri Gregor K. Wenning 《Clinical autonomic research》2016,26(2):97-105
Objective
Supine hypertension (SH) is a feature of cardiovascular autonomic failure that often accompanies orthostatic hypotension and may represent a negative prognostic factor in parkinsonian syndromes. Here we investigated the frequency rate as well as the clinical and tilt test correlates of SH in Parkinson’s disease (PD) and multiple system atrophy (MSA).Methods
197 PD (33 demented) and 78 MSA (24 MSA-Cerebellar, 54 MSA-Parkinsonian) patients who had undergone a tilt test examination were retrospectively included. Clinical-demographic characteristics were collected from clinical records at the time of the tilt test examination.Results
SH (>140 mmHg systolic, >90 mmHg diastolic) occurred in 34 % of PD patients (n = 66, mild in 71 % of patients, moderate in 27 %, severe in 2 %) and 37 % of MSA ones (n = 29, mild in 55 % of patients, moderate in 17 %, severe in 28 %). No difference was observed in SH frequency between demented versus gender-, age- and disease duration-matched non-demented PD patients, or between patients with the parkinsonian (MSA-P) versus the cerebellar (MSA-C) variant of MSA. In PD, SH was associated with presence of cardiovascular comorbidities (p = 0.002) and greater systolic (p = 0.007) and diastolic (p = 0.002) orthostatic blood pressure fall. Orthostatic hypotension (p = 0.002), and to a lesser degree, lower daily dopaminergic intake (p = 0.01) and use of anti-hypertensive medications (p = 0.04) were associated with SH in MSA.Interpretation
One-third of PD and MSA patients suffer from mild to severe SH, independently of age, disease duration or stage. In PD, cardiovascular comorbidities significantly contribute to the development of SH, while in MSA, SH appears to reflect cardiovascular autonomic failure.9.
Objective
To review existing evidence regarding interactions between the autonomic nervous system and the immune system functions in multiple sclerosis.Methods
We reviewed the literature regarding new insights linking autonomic dysfunction to immune deregulation in multiple sclerosis, with particular focus on the specific influence of sympathetic and parasympathetic dysfunction on inflammatory and neurodegenerative processes.Results
Autonomic dysfunction is common in multiple sclerosis, representing a significant cause of disability. Several connections between pathologic immune pathways and the autonomic nervous system function were found.Conclusions
Autonomic dysfunction may enhance inflammatory and neurodegenerative pathways that are of major importance in multiple sclerosis. Autonomic dysfunction can present with highly variable manifestations. Sympathetic and parasympathetic dysfunction displays different patterns in multiple sclerosis, with specific impact on inflammation and neurodegeneration.10.
Francisco Javier Carod-Artal 《Clinical autonomic research》2018,28(1):67-81
Objectives
To review infectious diseases that may cause autonomic dysfunction.Methods
Review of published papers indexed in medline/embase.Results
Autonomic dysfunction has been reported in retrovirus (human immunodeficiency virus (HIV), human T-lymphotropic virus), herpes viruses, flavivirus, enterovirus 71 and lyssavirus infections. Autonomic dysfunction is relatively common in HIV-infected patients and heart rate variability is reduced even in early stages of infection. Orthostatic hypotension, urinary dysfunction and hypohidrosis have been described in tropical spastic paraparesis patients. Varicella zoster reactivation from autonomic ganglia may be involved in visceral disease and chronic intestinal pseudo-obstruction. Autonomic and peripheral nervous system dysfunction may happen in acute tick-borne encephalitis virus infections. Hydrophobia, hypersalivation, dyspnea, photophobia, and piloerection are frequently observed in human rabies. Autonomic dysfunction and vagal denervation is common in Chagas disease. Neuronal depopulation occurs mainly in chagasic heart disease and myenteric plexus, and megacolon, megaesophagus and cardiomyopathy are common complications in the chronic stage of Chagas disease. Parasympathetic autonomic dysfunction precedes left ventricle systolic dysfunction in Chagas disease. A high prevalence of subclinical autonomic neuropathy in leprosy patients has been reported, and autonomic nerve dysfunction may be an early manifestation of the disease. Autonomic dysfunction features in leprosy include anhidrosis, impaired sweating function, localised alopecia ,and reduced heart rate variability. Urinary retention and intestinal pseudo-obstruction have been described in Lyme disease. Diphtheritic polyneuropathy, tetanus and botulism are examples of bacterial infections releasing toxins that affect the autonomic nervous system.Conclusions
Autonomic dysfunction may be responsible for additional morbidity in some infectious diseases.11.
Yhojan Rodríguez Manuel Rojas Carolina Ramírez-Santana Yeny Acosta-Ampudia Diana M. Monsalve Juan-Manuel Anaya 《Clinical autonomic research》2018,28(2):211-214
Purpose
To determine if autonomic symptoms are associated with previous Zika virus infection.Methods
Case–control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31).Results
Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001).Conclusion
Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.12.
E. Zirek Burcu Ersoz Huseyinsinoglu Z. Tufekcioglu B. Bilgic H. Hanagasi 《Neurological sciences》2018,39(12):2151-2157
Background
There is evidence that cognitive load has a negative effect on the gait of patients with Parkinson’s disease (PD). However, it is not clear which type of cognitive activities are more likely to affect dual-task abilities in this patient group.Aims
To compare the cognitive dual-task abilities in patients with PD and control subjects and to analyze the effect of different cognitive activities on the walking ability of patients with PD.Methods
The Hoehn and Yahr scale, the Freezing of Gait Questionnaire (FOGQ), Montreal Cognitive Assessment (MoCA), and the Functional Reach Test were used to include and exclude the patients. The Timed Up and Go (TUG) test was applied under single and dual-task conditions.Results
The completion time of TUG was found to be increased in the PD group compared with the healthy controls under single- and dual-task conditions (p?<?0.05). The completion time of TUG was significantly increased in dual-task conditions with complex attention activity (serial subtractions test) compared with other dual-task conditions in patients with PD (p?<?0.001).Discussion
The gait performance of both healthy subjects and patients with PD was impaired with cognitive activity during walking, and patients with PD showed more impairment under different cognitive dual tasks. Among the other cognitive tasks, the ‘serial sevens’ test, a measure of complex attention, significantly increased the completion time of TUG.Conclusions
While assessing the dual-task ability of patients with early-stage PD, tasks that increase the demand for complex attention seem to be more sensitive to showing impaired dual-task ability.13.
SuoYu Zhu TianHong Zhang ChengQing Yang YanYan Wei LiHua Xu JunJie Wang Annabelle Chow XiaoHua Liu KaiDa Jiang ZePing Xiao Hui Zhou JiJun Wang 《Social psychiatry and psychiatric epidemiology》2018,53(1):99-106
Objective
This study aimed to examine the overlaps between the Diagnostic and Statistical Manual-5 (DSM-5) Personality Disorders (PDs) in a high-risk clinical population and to explore a transitional model for implementing DSM-5 PDs.Method
A sample population of 982 outpatients with at least one diagnosed PD was selected from 3,075 outpatients of the Shanghai Mental Health Center. The diagnostic process comprised of a personality diagnostic questionnaire and a structured clinical interview.Results
685 (22.3%) patients were diagnosed with at least one of six PDs (antisocial, avoidant, borderline, narcissistic, obsessive–compulsive, and schizotypal) under the alternative DSM-5 model for personality disorders proposed in Section III of the DSM-5. Nearly 20.3% of the subjects with PD met criteria for at least two PDs (of the 685 PD patients/6 PD model). Cluster and principal component analyses suggest a transitional model for the 7 specific PD categories (among the 722 PD patients, the overlapping rate was 24.1%) will be more appropriate for PD diagnosis in China.Conclusions
Using the simplified PD categories in the alternative DSM-5 model for personality disorders will reduce the overlaps in PD diagnoses in Chinese psychiatric practice, and should be preferred over the DSM-5 PD diagnostic system.14.
Background
Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited.Objectives
The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer’s disease (AD), Parkinson’s disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA).Methods
Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n?=?131), PD (n?=?63), MCI (n?=?46), and HOA (n?=?62), controlling for age and sex.Results
All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA.Conclusions
Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.15.
Mike Arnhold Yanina Dening Michaël Chopin Esteban Arévalo Mathias Schwarz Heinz Reichmann Gabriele Gille Richard H. W. Funk Francisco Pan-Montojo 《Clinical autonomic research》2016,26(3):211-222
Introduction
Involvement of the peripheral nervous system (PNS) is relatively common in Parkinson’s disease (PD) patients. PNS alterations appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients. In previous studies, we have shown that environmental toxins can trigger the disease by acting on the enteric nervous system.Material and methods
Here, we analyzed the effect of mitochondrial Complex I inhibition on sympathetic neuritis in vivo and sympathetic neurons in vitro. Combining in vivo imaging and protein expression profiling.Results
we found that rotenone, a widely used mitochondrial Complex I inhibitor decreases the density of sympathetic neurites innervating the gut in vivo, while in vitro, it induces the redistribution of intracellular alpha-synuclein and neurite degeneration. Interestingly, sympathetic neurons are much more resistant to rotenone exposure than mesencephalic dopaminergic neurons.Conclusion
Altogether, these results suggest that enteric sympathetic denervation could be an initial pre-motor alteration in PD progression that could be used as an early biomarker of the disease.16.
Anne Schienle Axel Wolf Peter Valentin Tomazic Rottraut Ille 《Chemosensory perception》2018,11(2):72-76
Introduction
Olfactory dysfunction can have a negative impact on emotional well-being. The aim of the present study was to examine associations between olfactory deficits and two affective personality characteristics (trait anxiety/trait depression).Methods
A questionnaire study was conducted with a total of 116 participants (33 classified as anosmic, 40 as hyposmic, and 39 as normosmic). All participants gave self-reports on two facets of trait depression (dysthymia, euthymia) and trait anxiety (arousal, worrying). Due to the fact that in all three groups, trait depression and anxiety were substantially correlated, analyses of covariance were conducted.Results
After controlling for trait depression, anosmic and hyposmic patients showed lower trait arousal compared to normosmic controls (partial η 2?=?.05). After controlling for trait anxiety, patients scored higher on dysthymia (partial η 2?=?.06).Conclusions
This study underlines the importance of statistically isolating specific associations between each of these affective personality characteristics and olfactory dysfunction.Implications
The present findings suggest that olfactory dysfunction can have opposite effects on facets of trait depression and trait anxiety.17.
Objective
The variability of the severity and regional distribution of pathological process in basal ganglia (BG) and brainstem–cerebellar systems results in clinical heterogeneity and represents the motor subtype of multiple system atrophy (MSA). This study aimed to quantify spatial patterns of multimodal MRI abnormalities in BG and stem-CB regions and define structural MRI findings that correlate with clinical characteristics.Methods
We simultaneously measured R2*, mean diffusivity (MD), and volume in the subcortical structures (BG, thalamus, brainstem–cerebellar regions) of 39 probable MSA and 22 control subjects. Principal component analysis (PCA) and structural equation modeling (SEM) were performed to show a model consisting of multiple inter-dependencies.Results
Structural MRI alterations were found to be significantly interrelated within BG as well as brainstem–cerebellar regions in MSA patients. PCA extracted four factors: three factors reflected alterations in R2*, MD and volume of the BG region including the caudate nucleus, putamen, and pallidum, and the remaining one factor represented degenerative changes in MD and volume of stem-CB region. In SEM, a latent variable reflecting brainstem–cerebellar degeneration did not show a significant correlation with the other latent variables associated with BG degeneration. Putaminal MD values and a PCA-driven factor reflecting MD values in the BG showed a significant correlation with UPDRS and UMSARS scores.Conclusion
Multimodal structural MRI abnormalities in MSA appear to be segregated into BG and stem-CB-related factors that can be associated with the clinical phenotype and motor severity.18.
Purpose
The initial symptoms of multiple system atrophy (MSA) and, in particular, early autonomic symptoms, have received less attention than motor symptoms. Whereas pathognomonic motor signs are essential to diagnostic specificity, early symptoms important to recognition of a neurodegenerative disorder may be less apparent or diagnostically ambiguous. This observational study sought to identify the very earliest symptoms in the natural history of MSA.Methods
Detailed clinical histories focusing on early symptoms were obtained from 30 subjects recently diagnosed with MSA. Historical data were correlated with neurological examinations and laboratory autonomic testing.Results
Subjects’ mean age was 63.9 years. Ten were classified as having MSA-P and 20 MSA-C. The evaluations occurred 2.9 ± 0.4 months after diagnosis. The first symptom of MSA was autonomic in 22 (73%) and motor in 3 (10%) subjects (p < 0.0001). The most frequent first symptom was erectile failure, which occurred in all men beginning 4.2 ± 2.6 years prior to diagnosis. After erectile failure, postural lightheadness or fatigue following exercise, urinary urgency or hesitancy, and violent dream enactment behavior consistent with REM behavioral sleep disorder were the most frequent initial symptoms. Neither the order of symptom progression, which was highly variable, nor autonomic severity scores differentiated between MSA-P and MSA-C.Conclusions
The first symptoms of MSA are frequently autonomic and may predate recognition of motor manifestations. Orthostatic hypotension and, in men, erectile failure are among the first symptoms that, when evaluated in the context of associated clinical findings, may facilitate accurate and earlier diagnosis.19.
Tuba Özcan Erdal Benli Feriha Özer Esra Yancar Demir Yasemin Kaya Ali Ayyıldız 《Clinical autonomic research》2016,26(3):205-209