Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

Cersósimo, María G.; Benarroch, Eduardo E.

doi:10.1016/j.jns.2011.09.030

Cited by 116 publications

(80 citation statements)

References 124 publications

(237 reference statements)

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“…This symptom has been attributed to a sympathetic denervation of the heart or vasculature. [5][6][7][8][9] In some PD and dementia with Lewy bodies patients, Lewy pathology is present in the peripheral vagal nerve and ganglia. 10,11 These axons originate in the DMV.…”

Section: Introductionmentioning

confidence: 99%

“…11 Djaldetti and colleagues have reported a marked denervation of all autonomic neurites in skin, 13 work supported by analyses of skin biopsies from PD patients. 5,14 Lewy pathology and dopaminergic neuron loss also has been found in the enteric nervous system of many PD patients, particularly the lower gastrointestinal tract, which might be responsible for decreased gastric motility and constipation. 15,16 The inevitability of enteric nervous system pathology in PD has been challenged, however.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18][19] These studies show that enteric nervous system Lewy pathology is a frequent, but not necessary concomitant of PD. Conversely, although gastrointestinal dysfunction is frequently found in PD patients, 5 it is also common among aged individuals without any sign of PD. 20 Making matters worse, enteric nervous system neurons are very heterogeneous and attempts to identify the phenotype of those exhibiting Lewy pathology have not reached a consensus.…”

Section: Introductionmentioning

confidence: 99%

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The pathology roadmap in Parkinson disease

Surmeier¹,

Sulzer

2013

Prion

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The pathology roadmap in Parkinson disease

Surmeier¹,

Sulzer

2013

Prion

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“…Non-motor signs: prevalence, respective level of functional disability and potential role as premotor signs of Parkinson's disease 15,16,17,18,19,35,43,44,45,47,48,49,51,52,53,60 . healthy elderly individuals, those with proven olfactory deficit had a higher risk of developing symptomatic PD clinical and when they remained asymptomatic, these individuals presented LB in the SNc on post-mortem examination.…”

Section: Olfactory Deficitmentioning

confidence: 99%

“…Thus, from the pathophysiological point of view, constipation may reflect not only this peripheral involvement but also central mechanisms that cause pelvic floor dysfunction. Some of these individuals with peripheral autonomic disorder still present LB in the central nervous system and others have other pre-motor signs such as RBD, striatal abnormalities in functional tests or even pre-diagnostic PD as described above, in another words, the presence of a subtle cardinal sign that did not fill formal criteria for PD 47,48 .…”

Section: Constipationmentioning

confidence: 99%

Non-motor signs in Parkinson’s disease: a review

Munhoz

Moro

Silveira‐Moriyama

et al. 2015

Arq. Neuro-Psiquiatr.

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The traditional pathological description of PD as a pre-synaptic degenerative process affecting dopaminergic neurons in the substantia nigra pars compacta (SNc) of the midbrain with formation of Lewy bodies (LB) has changed dramatically in the last decade since functional and neuropathological studies showed the occurrence of extensive extranigral involvement 1 . Among these investigations, the seminal study of Braak et al. 2 suggested that the degenerative process in the PD starts in the caudal regions of the brainstem and the olfactory bulb, progressing in the caudal-rostral direction. The involvement of the SNc occurs, according to this hypothesis, on the third of a six-stage process that begins in the dorsal motor nuclei of the glossopharyngeal and vagus nerves and the olfactory bulb. Although it demonstrates the occurrence of this peculiar pathological distribution, the study fails to make the clinical correlation between any of these changes and motor or non-motor manifestations. On the other hand, even considering this caveat, it was one of the studies that formed the basis and motivated the dissemination of the concept of the existence of non-motor signs (NMS), especially dysautonomia, olfaction and sleep disorders, as part of the disease, sometimes even preceding the classic motor symptoms of PD.The motor aspects of PD typically have a slow progression and direct correlation with the presence of neuronal degeneration in the SNc, but they do not represent the actual beginning of the degenerative process. This process is, in fact, in full progression, despite been apparently silent when one seeks only for motor signs 3 . EXTRANIGRAL DEGENERATIONThe notion of PD as a multisystemic disease, not restricted to the nigrostriatal tract is not new, however the cited ABSTRACTDuring the past decade the view of Parkinson's disease (PD) as a motor disorder has changed significantly and currently it is recognized as a multisystem process with diverse non-motor signs (NMS). In addition to been extremely common, these NMS play a major role in undermining functionality and quality of life. On the other hand, NMS are under recognized by physicians and neglected by patients. Here, we review the most common NMS in PD, including cognitive, psychiatric, sleep, metabolic, and sensory disturbances, discuss the current knowledge from biological, epidemiological, clinical, and prognostic standpoints, highlighting the need for early recognition and management.Keywords: Parkinson's disease, non-motor signs, dementia, hyposmia, psychosis. RESUMONo decorrer da última década, a visão da doença de Parkinson (DP) como um distúrbio de movimento puro mudou significativamente, sendo atualmente reconhecida como um processo multisistêmico com diversos sinais não motores (SNM). Além de serem extremamente comuns, estes SNM têm um impacto muito significativo na limitacão funcional e da qualidade de vida na DP. Por outro lado, os SNM são mal reconhecidos pelos clínicos e negligenciados pelos pacientes. Nessa revisão os SNM mais comuns na DP fo...

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Cardioselective peripheral noradrenergic deficiency in Lewy body synucleinopathies

Lamotte

Holmes

Sullivan

et al. 2020

Ann Clin Transl Neurol

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Objective: Lewy body (LB) synucleinopathies such as Parkinson's disease (PD) entail profound cardiac norepinephrine deficiency. The status of sympathetic noradrenergic innervation at other extracranial sites has been unclear. Although in vivo neuroimaging studies have indicated a cardioselective noradrenergic lesion, no previous study has surveyed peripheral organs for norepinephrine contents in LB diseases. We reviewed 18 F-dopamine (18 F-DA) positron emission tomographic images and postmortem neurochemical data across several body organs of controls and patients with the LB synucleinopathies PD and pure autonomic failure (PAF) and the non-LB synucleinopathy multiple system atrophy (MSA). Methods: 18 F-DA-derived radioactivity in the heart, liver, spleen, pancreas, stomach, kidneys, thyroid, and submandibular glands were analyzed from 145 patients with LB synucleinopathies (112 PD, 33 PAF), 74 controls, and 85 MSA patients. In largely separate cohorts, postmortem tissue norepinephrine data were reviewed for heart, liver, spleen, pancreas, kidney, thyroid, submandibular gland, and sympathetic ganglion tissue from 38 PD, 2 PAF, and 5 MSA patients and 35 controls. Results: Interventricular septal 18 F-DA-derived radioactivity was decreased in the LB synucleinopathy group compared to the control and MSA groups (P < 0.0001 each). The LB and non-LB groups did not differ in liver, spleen, pancreas, stomach, or kidney 18 F-DA-derived radioactivity. The LB synucleinopathy group had markedly decreased apical myocardial norepinephrine, but normal tissue norepinephrine in other organs. The MSA group had normal tissue norepinephrine in all examined organs. Interpretation: By in vivo sympathetic neuroimaging and postmortem neurochemistry peripheral noradrenergic deficiency in LB synucleinopathies is cardioselective. MSA does not involve peripheral noradrenergic deficiency.

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Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

Cited by 116 publications

References 124 publications

The pathology roadmap in Parkinson disease

The pathology roadmap in Parkinson disease

Non-motor signs in Parkinson’s disease: a review

Cardioselective peripheral noradrenergic deficiency in Lewy body synucleinopathies

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