Peripheral Autonomic Nervous System Research Articles

Effects of ischaemic conditioning on tissue oxygen saturation and heart rate variability: an observational study.

ObjectiveIschaemic conditioning (IC) has organ-protective effects, but its clinical results have been inconsistent. Tissue oxygen saturation (StO2) and heart rate variability (HRV) reflect peripheral microcirculation and autonomic nervous system activity, but their changes during IC have not been well documented. We assessed StO2 and HRV during IC in patients undergoing cardiac surgery and healthy volunteers.MethodsTen patients undergoing cardiac surgery and 10 healthy male volunteers underwent remote IC (four 5-minute cycles of ischaemia/reperfusion) applied to the upper arm. Changes in StO2 at the thenar eminence and HRV according to the R-R intervals were recorded during IC.ResultsThe lowest StO2 during ischaemia significantly decreased in patients and significantly increased in volunteers. Among the HRV parameters, the low-frequency domain, which corresponds to sympathetic activity, significantly increased after IC in volunteers but not in patients. Other variables were similar between the groups.ConclusionsThese results suggest that the minimum tissue oxygen content is depleted during ischaemia in patients and preserved in healthy volunteers. Sympathetic nervous activity seems to increase after IC in healthy volunteers but remains unaffected in patients. Thus, IC may act differently between patients undergoing cardiac surgery and healthy subjects.

Autoimmune autonomic neuropathies and ganglionopathies: epidemiology, pathophysiology, and therapeutic advances.

Autonomic disorders can be the result of autoimmunity. The classic, well-characterized example is autoimmune autonomic ganglionopathy (AAG), in which antibodies against the ganglionic nicotinic acetylcholine receptor impair autonomic transmission, causing autonomic failure, which responds to immunotherapy. However, a number of other autoimmune disorders cause autonomic failure through a variety of mechanisms. In this article, we review autoimmune disorders causing impairment of the peripheral autonomic nervous system (ganglia and nerves), including AAG, other autoimmune autonomic neuropathies, paraneoplastic autonomic neuropathies, and neuromuscular and rheumatologic diseases with autonomic symptomatology. Awareness of primary autoimmune autonomic disorders and the autonomic manifestations of other autoimmune diseases promotes timely diagnosis and appropriate management, including supportive care for unpleasant or dangerous autonomic dysfunction, a search for underlying malignancy when indicated, and the use of immunotherapy when appropriate. A better understanding of the underlying pathophysiology aids in the judicious use and selection of immunotherapy.

Scorpion venom increases acetylcholine release by prolonging the duration of somatic nerve action potentials

Scorpionism is frequently accompanied by a massive release of catecholamines and acetylcholine from peripheral nerves caused by neurotoxic peptides present in these venoms, which have high specificity and affinity for ion channels. Tityus bahiensis is the second most medically important scorpion species in Brazil but, despite this, its venom remains scarcely studied, especially with regard to its pharmacology on the peripheral (somatic and autonomic) nervous system. Here, we evaluated the activity of T. bahiensis venom on somatic neurotransmission using myographic (chick and mouse neuromuscular preparations), electrophysiological (MEPP, EPP, resting membrane potentials, perineural waveforms, compound action potentials) and calcium imaging (on DRG neurons and muscle fibres) techniques. Our results show that the major toxic effects of T. bahiensis venom on neuromuscular function are presynaptically driven by the increase in evoked and spontaneous neurotransmitter release. Low venom concentrations prolong the axonal action potential, leading to a longer depolarization of the nerve terminals that enhances neurotransmitter release and facilitates nerve-evoked muscle contraction. The venom also stimulates the spontaneous release of neurotransmitters, probably through partial neuronal depolarization that allows calcium influx. Higher venom concentrations block the generation of action potentials and resulting muscle twitches. These effects of the venom were reversed by low concentrations of TTX, indicating voltage-gated sodium channels as the primary target of the venom toxins. These results suggest that the major neuromuscular toxicity of T. bahiensis venom is probably mediated mainly by α- and β-toxins interacting with presynaptic TTX-sensitive ion channels on both axons and nerve terminals.

The relationship between heart rate and functional connectivity of brain regions involved in autonomic control

The peripheral autonomic nervous system (ANS) adjusts the heart rate (HR) to intrinsic and extrinsic demands. It is controlled by a group of functionally connected brain regions assembling the so-called central autonomic network (CAN). More specifically, forebrain cortical regions, limbic and brainstem structures within the CAN have been identified as important components of circuits involved in HR regulation. The present study aimed to investigate whether functional connectivity (FC) between these regions varies in subjects with different heart rates. Thus, 84 healthy subjects were separated according to their HR in slow, medium and fast. We observed a direct association between HR and FC in CAN regions, where stronger FC was related to slower HR. This relationship, however, is non-linear, follows an exponential course and is not restricted to CAN areas only. The network-based analysis (NBS) using time series from 262 independent anatomical ROIs revealed significantly increased functional connectivity in subjects with slow HR compared to subjects with fast HR mainly in regions being part of the salience network, but also of the default-mode network. We additionally simulated the effect of aliasing on the functional connectivity using several TRs and heart rates to exclude the possibility that FC differences might be due to different aliasing effects in the data. The result of the simulation indicated that aliasing cannot explain our findings.Thus, present results imply a functionally meaningful coupling between FC and HR that need to be accounted for in future studies. Moreover, given the established link between HR and emotional, cognitive and social processes, present findings may also be considered to explain individual differences in brain activation or connectivity when using corresponding paradigms in the MR scanner to investigate such processes.

Effects on Cardiac and Peripheral Autonomic Nervous System by Posture Respiration Feedback Control Architecture

Effects on Cardiac and Peripheral Autonomic Nervous System by Posture Respiration Feedback Control Architecture

'Point of no return' in diabetic neuropathies: a dangerous delusion

Polyneuropathy in patients with diabetes mellitus is manifested by a lesion of peripheral sensory, motor and autonomic nervous system. Different severity of damage of sensory, motor and autonomic fibers in typical and atypical forms of diabetic polyneuropathy, requires a differentiated approach to therapy, but not the rejection of its implementation. In an interdisciplinary consensus, consultations are held with physicians from different regions of the Russian Federation, and modern methods of diagnosing and assessing the severity of diabetic polyneuropathies, which determine the algorithm for treating patients, are discussed.

Chapter 27 - Pure autonomic failure

In this chapter, we describe the history, presentation, diagnosis and treatment of pure autonomic failure (PAF). The pathology underlying this condition is thought to involve the deposition of alpha synuclein in the autonomic ganglia leading to diminished norepinephrine release and progressive autonomic dysfunction. We focus on various neurophysiological tests that may be used to evaluate the function of the peripheral autonomic nervous system including quantitative sudomotor axon reflex testing, thermoregulatory sweat testing, and others. These may help evaluate and diagnose various disorders of autonomic failure and neurogenic orthostatic hypotension including multiple system atrophy and Parkinson's disease dysautonomia. Management of PAF, including the therapeutic role of recent advances in pharmacologic treatment, is discussed.

Anti-cholinergics mecamylamine and scopolamine alleviate motion sickness-induced gastrointestinal symptoms through both peripheral and central actions

Enhanced cholinergic activity contributes to the production of complex autonomic manifestations of motion sickness (MS). However, whether anti-cholinergics exert their anti-MS effects through central or peripheral actions remained unclarified. In the present study, we investigated the effects of mecamylamine (MEC) and scopolamine (SCOP) on rotation-induced gastrointestinal symptoms (conditioned gaping and defecation), locomotion disturbances (hypoactivity and impaired balance performance), hypothermia as well as Fos expression in vestibulo-autonomic regions in rats. We also observed the effects of hexamethonium (HEX) and methyl scopolamine (MSCP) on those MS behavioral responses. The efficacy of all these drugs on rotation-induced emesis and other MS symptoms in cats was also examined. We found that intragastric administration of MEC and SCOP inhibited rotation-induced gaping and defecation in rats, but only MEC showed a dose-dependent manner. MEC aggravated rotation-induced balance disorder and failed to attenuate rotation-induced hypothermia as the SCOP did. MEC was more effective for inhibiting Fos expression in the caudal vestibular nucleus and nucleus of solitary tract than SCOP. Intraperitoneal injection of HEX and MSCP also significantly alleviated rotation-induced gastrointestinal symptoms, and showed benefit to balance performance in rats. In cats, MEC, SCOP and HEX had prophylactic effects against rotation-induced emesis and salivation, and deceased non-retching/vomiting symptoms, but MSCP only attenuated emesis. It suggested that MEC and SCOP might alleviate gastrointestinal symptoms of MS via inhibiting peripheral autonomic nervous system and central vestibulo-autonomic pathways. The nicotinic acetylcholine receptor inhibitors like MEC might be new candidates against gastrointestinal symptoms induced by MS or other vestibular disorders.

What is the Evidence That Parkinson's Disease is a Prion Disorder, Which Originates in the Gut?

Parkinson’s disease (PD) is a neurodegenerative disorder resulting from degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). PD is characterized by motor dysfunctions as well as gastrointestinal symptoms and mental impairment. The pathological hallmark of PD is an accumulation of misfolded α-synuclein aggregates within the brain. The etiology of PD and related synucleinopathy is poorly understood, but recently, the hypothesis that α-synuclein pathology spreads in a prion-like fashion originating in the gut has gained much scientific attention. A crucial clue was the appearance of constipation before the onset of motor symptoms, gut dysbiosis and synucleinopathy in PD patients. Another line of evidence, demonstrating accumulation of α-synuclein within the peripheral autonomic nervous system (PANS), including the enteric nervous system (ENS), and the dorsal motor nucleus of the vagus (DMV) support the concept that α-synuclein can spread from the ENS to the brain by the vagus nerve. The decreased risk of PD following truncal vagotomy supports this. The convincing evidence of the prion-like behavior of α-synuclein came from postmortem observations that pathological α-synuclein inclusions appeared in healthy grafted neurons. In this review, we summarize the available data from human subjects’ research and animal experiments, which seem to be the most suggestive for explaining the hypotheses.

Imaging the Autonomic Nervous System in Parkinson's Disease.

Patients with Parkinson's disease (PD) often display gastrointestinal and genitourinary autonomic symptoms years or even decades prior to diagnosis. These symptoms are thought to be caused in part by pathological α-synuclein inclusions in the peripheral autonomic and enteric nervous systems. It has been proposed that the initial α-synuclein aggregation may in some PD patients originate in peripheral nerve terminals and then spread centripetally to the spinal cord and brainstem. In vivo imaging methods can directly quantify the degeneration of the autonomic nervous system as well as the functional consequences such as perturbed motility. Here, we review the methodological principles of these imaging techniques and the major findings in patients with PD and atypical parkinsonism. Loss of sympathetic and parasympathetic nerve terminals in PD can be visualized using radiotracer imaging, including 123I-MIBG scintigraphy, and 18F-dopamine and 11C-donepezil PET. Recently, ultrasonographical studies disclosed reduced diameter of the vagal nerves in PD patients. Radiological and radioisotope techniques have demonstrated dysmotility and prolonged transit time throughout all subdivisions of the gastrointestinal tract in PD. The prevalence of objective dysfunction as measured with these imaging methods is often considerably higher compared to the prevalence of subjective symptoms experienced by the patients. Degeneration of the autonomic nervous system may play a key role in the pathogenesis of PD. In vivo imaging techniques provide powerful and noninvasive tools to quantify the degree and extent of this degeneration and its functional consequences.

Colonic neuropathology is not associated with autonomic dysfunction in Parkinson's disease

IntroductionDysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonic alpha-synuclein histopathology is associated with dysautonomia in PD. MethodsA total of 43 PD patients participated in this study. For each patient, two biopsies were taken in the sigmoid colon and analyzed by immunohistochemistry with antibodies against phosphorylated alpha-synuclein and PGP 9.5. All patients had a complete neuropsychological and neurological assessment along with a comprehensive evaluation of dysautonomia with questionnaires (SCOPA-Aut, NMS-Quest, Rome III constipation criteria and dry eye symptoms) and functional tests (pupillometry, Saxon and Schirmer's tests, heart rate variability, orthostatic blood pressure measure and sympathetic skin response). ResultsColonic PASH was observed in 20/43 PD patients. No differences were observed in autonomic symptoms and testing between patients with and without PASH. ConclusionsAlthough frequent in PD, autonomic dysfunction is not related to colonic PASH. In addition to the existing literature, our findings further suggest that each dysautonomic symptom in PD might not be associated with a more severe or diffuse PASH not only in the central nervous system but also in the peripheral autonomic nervous systems.

Autonomic Dysfunction and Skin Biopsy in Dementia with Lewy Bodies

Neuropathological hallmarks of Lewy body disease including Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy bodies in not only the central nervous system but also the peripheral autonomic nervous system. α-synuclein is a presynaptic protein, and is a major constituent of Lewy bodies. The peripheral autonomic nervous system innervates various organs such as the gastrointestinal tract, the heart, the bladder, and the skin. Severe autonomic dysfunction is one of the supportive clinical features of DLB, and reduced cardiac MIBG uptake is an indicative biomarkers of DLB according to the revised criteria for the clinical diagnosis of DLB in 2017. Recently, it was reported that α-synuclein deposits in various biopsied tissue samples, particularly in the skin, can act as a possible biomarker to diagnose PD. Above approach was conducted by using skin biopsies from patients with DLB. Phosphorylated α-synuclein deposits in the skin were found in all patients with DLB, but not in patients with non-synucleinopathy dementia or controls, suggesting that phosphorylated α-synuclein can potentially act as a diagnostic biomarker in DLB.

Peripheral and central autonomic nervous system: does the sympathetic or parasympathetic nervous system bear the brunt of the pathology during the course of sporadic PD?

It is a well-established fact that the sympathetic, parasympathetic and enteric nervous systems are affected at early stages in Parkinson's disease (PD). However, it is not yet clarified whether the earliest pathological events preferentially occur in any of these three divisions of the autonomic nervous system (ANS). Significant involvement of the peripheral autonomic nervous system of the heart and gastrointestinal tract has been documented in PD. Accumulating evidence suggests that the PD pathology spreads centripetally from the peripheral to central nervous system through autonomic nerve fibers, implicating the ANS as a major culprit in PD pathogenesis and a potential target for therapy. This study begins with a brief overview of the structures of the central and peripheral autonomic nervous system and then outlines the major clinicopathological manifestations of cardiovascular and gastrointestinal disturbances in PD.

In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study

Accumulating evidence suggests that α-synuclein aggregates-a defining pathology of Parkinson's disease-display cell-to-cell transmission. α-synuclein aggregation is hypothesised to start in autonomic nerve terminals years before the appearance of motor symptoms, and subsequently spread via autonomic nerves to the spinal cord and brainstem. To assess this hypothesis, we investigated sympathetic, parasympathetic, noradrenergic, and dopaminergic innervation in patients with idiopathic rapid eye movement (REM) sleep behaviour disorder, a prodromal phenotype of Parkinson's disease. In this prospective, case-control study, we recruited patients with idiopathic REM sleep behaviour disorder, confirmed by polysomnography, without clinical signs of parkinsonism or dementia, via advertisement and through sleep clinics in Denmark. We used 11C-donepezil PET and CT to assess cholinergic (parasympathetic) gut innervation, 123I-metaiodobenzylguanidine (MIBG) scintigraphy to measure cardiac sympathetic innervation, neuromelanin-sensitive MRI to measure integrity of pigmented neurons of the locus coeruleus, 11C-methylreboxetine (MeNER) PET to assess noradrenergic nerve terminals originating in the locus coeruleus, and 18F-dihydroxyphenylalanine (DOPA) PET to assess nigrostriatal dopamine storage capacity. For each imaging modality, we compared patients with idiopathic REM sleep behaviour disorder with previously published reference data of controls without neurological disorders or cognitive impairment and with symptomatic patients with Parkinson's disease. We assessed imaging data using one-way ANOVA corrected for multiple comparisons. Between June 3, 2016, and Dec 19, 2017, we recruited 22 consecutive patients with idiopathic REM sleep behaviour disorder to the study. Compared with controls, patients with idiopathic REM sleep behaviour disorder had decreased colonic 11C-donepezil uptake (-0·322, 95% CI -0·112 to -0·531; p=0·0020), 123I-MIBG heart:mediastinum ratio (-0·508, -0·353 to -0·664; p<0·0001), neuromelanin-sensitive MRI locus coeruleus:pons ratio (-0·059, -0·019 to -0·099; p=0·0028), and putaminal 18F-DOPA uptake (Ki; -0·0023, -0·0009 to -0·0037; p=0·0013). No between-group differences were detected between idiopathic REM sleep behaviour disorder and Parkinson's disease groups with respect to 11C-donepezil (p=0·39), 123I-MIBG (p>0·99), neuromelanin-sensitive MRI (p=0·96), and 11C-MeNER (p=0·56). By contrast, 15 (71%) of 21 patients with idiopathic REM sleep behaviour disorder had 18F-DOPA Ki values within normal limits, whereas all patients with Parkinson's disease had significantly decreased 18F-DOPA Ki values when compared with patients with idiopathic REM sleep behaviour disorder (p<0·0001). Patients with idiopathic REM sleep behaviour disorder had fully developed pathology in the peripheral autonomic nervous system and the locus coeruleus, equal to that in diagnosed Parkinson's disease. These patients also showed noradrenergic thalamic denervation, but most had normal putaminal dopaminergic storage capacity. This caudorostral gradient of dysfunction supports the hypothesis that α-synuclein pathology in Parkinson's disease initially targets peripheral autonomic nerves and then spreads rostrally to the brainstem. Lundbeck Foundation, Jascha Foundation, and the Swiss National Foundation.

2298 Central autonomic network dysfunction implicated in alcohol-related intimate partner violence

OBJECTIVES/SPECIFIC AIMS: Most incidents of partner violence occur when one or both partners have been drinking, however, the mechanism through which this association exists is unclear. The neural circuits that support self-regulation of emotion and social behavior, as well as autonomic influences on the heart, are co-localized in the brain and represent an integrated bidirectional regulatory system. These physiological regulatory processes are mediated by a neural substrate known as the central autonomic network which includes the peripheral autonomic nervous system. The central autonomic network modulates biobehavioral resources in emotion by flexibly responding to physiological arousal in response to changing situational demands, and serves a fundamental role in emotion regulation and goal-directed motor behavior, and this circuit can be indexed with heart rate variability (HRV). METHODS/STUDY POPULATION: In total, 17 distressed violent (DV) partners (11 females, 6 males) were matched to a sample of distressed nonviolent (DNV) partners (7 female, 6 males) were matched on age, sex, and relationship satisfaction and participated in a placebo-controlled alcohol administration study with an emotion-regulation task during which electroencephalography, HRV, and galvanic skin response (GSR) measures were collected. In the alcohol condition, participants were administered a mixture of 100 proof vodka and cranberry juice calculated to raise their blood alcohol concentration to 0.08%. In the placebo condition, participants consumed a volume of juice equivalent to that consumed in the alcohol condition, but without alcohol. Alcohol and placebo conditions were counter-balanced across participants as were the presentation the blocks of evocative and neutral partner stimuli and emotion-regulation condition (watch vs. do not react). RESULTS/ANTICIPATED RESULTS: Results show that DV partners show greater cortical arousal than DNV partners on measures event-related spectral perturbations, which are mean log event-loced deviations from baseline-mean power at each frequency of the electroencephalography power spectra, when intoxicated and viewing evocative partner stimuli in the “do not react” emotion regulation condition. Results also show a statistically significant 2 (alcohol vs. placebo)×2 (watch vs. do not react)×2 (DV partners vs. DNV partners) interaction of the respiratory sinus arrhythmia measure of HRV when viewing evocative partner behavior (F=7.102, p=0.019, partial η2=0.353). Findings indicate that DV partners have lower HRV than DNV partners across conditions, but particularly when acutely intoxicated and trying not to react to their partners’ evocative behavior. Similarly, results also show a statistically significantly 2 (alcohol vs. placebo)×2 (watch vs. do not react)×2 (DV partners vs. DNV partners) interaction on GSR (F=71.452, p=0.000, partial η2=0.749). GSR findings indicate that DV partners also have lower GSR when acutely intoxicated and trying not to react to their partners’ evocative behavior. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that increases in intimate partner violence under acute alcohol intoxication may be the result of dysfunction of the central autonomic network, especially when DV partners are trying to suppress a behavioral response to their partners’ evocative behavior in conflict. The neurophysiological patterns evidenced by DV partners is consistent with a state of vigilance to threat, and reduced ability inhibit prepotent, but inappropriate responses. They also suggest that HRV may be an important target for intervention with partner with a history of intimate partner violence. One method may be heart rate variability biofeedback which has been shown to increase parasympathetic nervous system functioning, autonomic stability, and emotion regulation.

STP Position Paper: Recommended Best Practices for Sampling, Processing, and Analysis of the Peripheral Nervous System (Nerves and Somatic and Autonomic Ganglia) during Nonclinical Toxicity Studies.

Peripheral nervous system (PNS) toxicity is surveyed inconsistently in nonclinical general toxicity studies. These Society of Toxicologic Pathology "best practice" recommendations are designed to ensure consistent, efficient, and effective sampling, processing, and evaluation of PNS tissues for four different situations encountered during nonclinical general toxicity (screening) and dedicated neurotoxicity studies. For toxicity studies where neurotoxicity is unknown or not anticipated (situation 1), PNS evaluation may be limited to one sensorimotor spinal nerve. If somatic PNS neurotoxicity is suspected (situation 2), analysis minimally should include three spinal nerves, multiple dorsal root ganglia, and a trigeminal ganglion. If autonomic PNS neuropathy is suspected (situation 3), parasympathetic and sympathetic ganglia should be assessed. For dedicated neurotoxicity studies where a neurotoxic effect is expected (situation 4), PNS sampling follows the strategy for situations 2 and/or 3, as dictated by functional or other compound/target-specific data. For all situations, bilateral sampling with unilateral processing is acceptable. For situations 1-3, PNS is processed conventionally (immersion in buffered formalin, paraffin embedding, and hematoxylin and eosin staining). For situation 4 (and situations 2 and 3 if resources and timing permit), perfusion fixation with methanol-free fixative is recommended. Where PNS neurotoxicity is suspected or likely, at least one (situations 2 and 3) or two (situation 4) nerve cross sections should be postfixed with glutaraldehyde and osmium before hard plastic resin embedding; soft plastic embedding is not a suitable substitute for hard plastic. Special methods may be used if warranted to further characterize PNS findings. Initial PNS analysis should be informed, not masked ("blinded"). Institutions may adapt these recommendations to fit their specific programmatic requirements but may need to explain in project documentation the rationale for their chosen PNS sampling, processing, and evaluation strategy.

Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.

Heterogeneous pattern of autonomic dysfunction in Parkinson's disease.

Dysautonomic symptoms are frequent non-motor complaints in patients with Parkinson's disease. Numerous neuropathological studies have shown that Lewy bodies and neurites, the pathological hallmarks of Parkinson's disease, are widely distributed throughout the peripheral autonomic nervous systems and across end organs. However, few investigations integrally explored the symptoms and physiology of dysautonomia in Parkinson's disease. We, therefore, performed a comprehensive evaluation of the autonomic function in a prospective group of 45 patients with idiopathic Parkinson's disease. Autonomic components (pupillomotor, tear, salivary, cardiovascular, digestive, urinary, sexual, sudomotor functions and skin sensitivity) were evaluated using questionnaires and functional tests. Skin biopsy was performed for intraepidermal nerve fibre density quantification. In addition, all patients underwent polysomnography and a complete neuropsychological and neurological assessment. The analysis association of autonomic components showed that dysautonomic signs and symptoms were heterogeneously distributed among patients. Skin denervation as assessed by intraepidermal nerve fibre density quantification was only associated with quantitative thermal sensory testing (OR=12.0, p=0.02), constipation (OR=5.5, p=0.01) and ocular dryness symptoms (OR=8.29, p=0.04). Cognitive alteration was associated with cardiovascular symptoms (OR=4.33, p=0.03) and dysfunction (OR=5.83, p=0.02) as well as with constipation (OR=5.38, p=0.02). Axial motor impairment and rapid eye movement (REM) sleep behaviour disorder were not related to any of the autonomic complaint or dysfunction. Our results show that autonomic functions are affected in a heterogeneous pattern in Parkinson's disease, thereby suggesting that the progression of autonomic dysfunction follows an erratic rather than a stepwise progression.

Lack of pathogenic potential of peripheral \u03b1-synuclein aggregates from Parkinson\u2019s disease patients

In Parkinson’s disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism. Supporting a pathogenic role for α-synuclein aggregates we have previously shown that LB purified from postmortem PD brains promote α-synuclein pathology and dopaminergic neurodegeneration when intracerebrally inoculated into wild-type mice. However, the pathogenic capacity of PD-derived peripheral α-synuclein aggregates remains unknown. Here we addressed this question using purified LB-type α-synuclein aggregates from postmortem PD stellate ganglia (SG), a paravertebral sympathetic ganglion that exhibits consistent and conspicuous Lewy pathology in all PD patients. In contrast to our previous findings using nigral LB extracts, intracerebral inoculation of SG-derived LB into mice did not trigger long-term nigrostriatal neurodegeneration nor α-synuclein pathology. The differential pathogenic capacities of central- and peripheral-derived α-synuclein aggregates appear independent of the absolute amount and basic biochemical properties of α-synuclein within these aggregates and may rely instead on differences in α-synuclein conformation and/or yet unrecognized brain region-specific intrinsic factors. Our results argue against a putative pathogenic capacity of peripheral α-synuclein aggregates to promote α-synuclein pathology in the brain, propagate between neuronal networks or induce neurodegeneration.

Diagnostic Paradox behind Facial Nerve Schwannoma

Background: Schwannomas are benign and slow growing tumors that arise from the Schwann cells which ensheath the axons of peripheral nerve, cranial nerve and autonomic nervous system. A schwannoma of facial nerve may originate from extra or intra cranial segments of the nerve. Most of the facial nerve schwannomas originate from intra-tympanic region. In decreasing order of their frequency, schwannomas were found along the tympanic, mastoid (vertical), labrynthine and meatal segments of the facial nerve. It is an extremely rare entity as malignant degeneration of schwannomas is not frequent. A high level of clinical suspicion with detailed neuro-otological and radiological studies play important role in preoperative diagnosis of schwannomas. Case presentation: We reported a case of 35-year-old male with progressive right sided facial asymmetry, sudden onset hearing loss and non-pulsatile tinnitus in right ear. The patient’s presentation and diagnostic examinations helped us to reach a provisional diagnosis though final diagnosis was done on the basis of histopathological examination of the excised tumor which was suggestive of facial nerve schwannoma. Conclusion: The rare and inconsistent clinical presentation and radiological pattern of facial schwannoma often leads to a delayed and indefinite diagnosis. The critical step in management of diverse lesion is diagnosis for the management of facial schwannoma. This report is about a challenging case of facial nerve schwannoma in intra-tympanic region which was diagnosed and managed in our institution.