Sympathetic and parasympathetic pupillary dysfunction in familial dysautonomia

Dütsch, Matthias; Hilz, Max J.; Rauhut, U; Solomon, Joel; Neundörfer, B.; Axelrod, Felicia B.

doi:10.1016/s0022-510x(01)00686-4

Cited by 26 publications

(25 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, the previously reported pupil findings were made in the absence of objective measurements or controlled stimulus presentation, so specific comparison with our pupillometry results cannot be made. Published reports of pupillary abnormalities in children with familial dysautonomia, another disorder of respiratory and autonomic regulation, also demonstrate a decrease in both SNS and PSNS response, but direct comparison is limited due to variation in testing protocol (19).…”

Section: Discussionmentioning

confidence: 99%

“…Pupillometry offers noninvasive, rapid, and objective measurements of pupillary function; these measurements serve as an ideal instrument to quantify ophthalmologic-specific ANSD. Pupillometry has been successfully used to evaluate ANSD in autonomic neuropathies (14)(15)(16), pediatric enuresis (17), heart failure (18), and familial dysautonomia (19) and has the potential for use in other pediatric disorders of respiratory and autonomic dysregulation. Although multiple factors can influence pupil diameter and response, with standardized conditions and intact afferent pathways, pupillometry allows for insight into efferent ANS pathways (14).…”

Section: Ongenital Central Hypoventilation Syndrome (Cchs) Ismentioning

confidence: 99%

See 1 more Smart Citation

Pupillometry in congenital central hypoventilation syndrome (CCHS): quantitative evidence of autonomic nervous system dysregulation

et al. 2012

View full text Add to dashboard Cite

INTRODUCTION: congenital central hypoventilation syndrome (cchs) is characterized by alveolar hypoventilation, autonomic nervous system (aNs) dysregulation (aNsD), and mutations in the paired-like homeobox 2B (PHOX2B) gene. aNsD in cchs affects multiple systems and includes ophthalmologic abnormalities. We hypothesized that quantitative pupil measures, obtained using pupillometry, would vary between cases with cchs and controls and within those with cchs by PHOX2B genotype. RESULTS: Measures known to be illustrative of sympathetic and parasympathetic response (prestimulus, maximum pupil diameter, percentage of pupil constriction after light stimulus, and average constriction and dilation velocities) were significantly reduced in those with cchs as compared with controls (all P < 0.05). DISCUSSION: These reductions are indicative of both sympathetic and parasympathetic deficits in cchs, which is in keeping with the role of PHOX2B in aNs development. an inverse linear relationship was apparent in pupil diameter and velocity measurements among the cases with cchs with the most common heterozygous PHOX2B polyalanine expansion repeat mutations, suggesting a graded phenotype/genotype dose response based on polyalanine repeat length. These results confirm our central hypotheses while offering the first objective measures of pupillary dysfunction and ophthalmologicspecific aNsD in cchs. METHODS: a total of 316 monocular measurements were taken under dark-adapted conditions with a fixed light stimulus from 22 PHOX2B mutation-confirmed cases with cchs and 68 healthy controls. C ongenital central hypoventilation syndrome (CCHS) ischaracterized by central alveolar hypoventilation with autonomic nervous system dysregulation (ANSD) and is diagnosed in the absence of primary pulmonary, cardiac, or neuromuscular disease or a brainstem lesion that can account for the full phenotype (1). Discovery of the CCHS disease-defining gene, pairedlike homeobox 2B (PHOX2B) (2-4), and appreciation of its role in both embryologic development and regulatory function of the autonomic nervous system (ANS) (5-7), has broadened the understanding of the CCHS phenotype. The majority of individuals with CCHS are heterozygous for PHOX2B polyalanine repeat expansion mutations (PARMs), with a range of 24-33 alanine bases on the affected allele (20 repeats is normal; normal genotype is 20/20). Missense, nonsense, frameshift, and stop codon mutations in the PHOX2B gene, referred to as nonpolyalanine repeat expansion mutations (NPARMs), account for the remaining mutations in CCHS. Quantitative assessment of the respiratory control and ANSD features of CCHS by PHOX2B genotype has identified a graded genotype-phenotype relationship between mutation repeat length and ventilatory requirements (3,4), Hirschsprung disease (8,9), neural crest tumors (8,9), and cardiac sinus pauses (10).Detailed understanding of the ANSD features in CCHS requires targeted investigation with objective measures of all organ systems served by the ANS. Ophthalmologic abnormalities th...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ongenital Central Hypoventilation Syndrome (Cchs) Ismentioning

confidence: 99%

Pupillometry in congenital central hypoventilation syndrome (CCHS): quantitative evidence of autonomic nervous system dysregulation

et al. 2012

View full text Add to dashboard Cite

show abstract

“…14,47,90,91 In order to obtain an impression about the autonomic system, the pupil diameter and its response to stimuli can be measured. 49,52,54,56,69,70 A method of automated pupillometry was used in this study to capture pupil responsiveness. Pupillometry has been previously used to measure the pupil and has been shown to be an easy, valid, and reliable method of assessing the nervous system without the presence of much examiner bias.…”

Section: Discussionmentioning

confidence: 99%

“…49,52,54,56,69,70 Fully automated pupillometry devices have been used previously in a number of studies investigating autonomic nervous system activity. 53,56,[71][72][73][74][75][76] The human eye has difficulties detecting differences of the pupil that are smaller than 1.0 mm.…”

Section: Automated Measuresmentioning

confidence: 99%

Immediate effects of a thoracic spine thrust manipulation on the autonomic nervous system: a randomized clinical trial

Sillevis¹,

Cleland²,

Hellman³

et al. 2010

Journal of Manual & Manipulative Therapy

View full text Add to dashboard Cite

Thoracic spine manipulation has been shown to be effective for the management of neck pain. The purpose of this study was to investigate the immediate effect of a T3-T4 spinal thrust manipulation on autonomic nervous system activity in subjects with chronic cervical pain. An additional aim was to determine if the manipulation resulted in an immediate pain relief in patients with chronic neck pain when compared to a placebo intervention. One hundred subjects with chronic neck pain were randomly assigned to receive either a thoracic thrust manipulation or a placebo intervention. The Friedman's test was used to evaluate the change in pupil diameter within both groups. The Wilcoxen signed-ranks test was used to explore pupil changes over time and to make paired comparisons of the pupil change between the groups. The MannWhitney U test was used to compare the change in pain perception for the chronic cervical pain group subjects receiving either the thrust manipulation or the placebo intervention. The results demonstrated that manipulation did not result in a change in sympathetic activity. Additionally, there was no significant difference in the subject's pain perception (P50.961) when comparing the effects of the thrust manipulation to the placebo intervention within this group of subjects with chronic neck pain. The clinical impression of this study is that manipulation of the thoracic spine may not be effective in immediately reducing pain in patients with chronic neck pain.

show abstract

“…Given the rich autonomic innervation to the iris, measurements of pupillary response to light offer the potential of an objective assessment of autonomic nervous system activity as have been shown by previous studies (Bitsios et al, 1996, Dütsch et al, 2002Bradley et al, 2008). …”

Section: Modulation Of Pupil Responses By the Autonomic Nervous Systemmentioning

confidence: 99%

The Influence of the Autonomic Nervous System on the Human Choroid

Sander¹

View full text Add to dashboard Cite

v AbstractThe impact of myopia is greater than just its optical consequences and in severe cases it can lead to a loss of vision. It is a highly prevalent eye disorder, with about one third of the population worldwide affected by this refractive error. Despite extensive research, the pathogenesis of myopia is still only partially understood. An improved knowledge of mechanisms underlying myopia is critical to developing new therapies to prevent myopia or to slow its progression.Although there is no fully effective and satisfactory myopia control treatment available, growing evidence has suggested that the choroid has a passive or active role in the regulation of eye growth and refractive error development. Numerous human and animal studies have shown that the retina can be moved forward or backward towards the image plane through changes in choroidal thickness, and these changes are likely to be associated in the longer term with eye growth and the development of refractive errors. As the choroid receives a rich innervation from the autonomic nervous system, many previous animal studies have utilized pharmacological agents and neurotoxins to elucidate the possible role of muscarinic signaling in the regulation of choroidal thickness, but only a few studies have investigated this issue in humans. An improved understanding of the mechanisms that control choroidal thickness may be important in developing new therapies for combating the development and progression of myopia.The research described in the thesis aimed to investigate the role of the autonomic nervous system in the control of choroidal thickness, axial length and the morphology In a series of experiments, we have confirmed that in humans under normal visual conditions, the parasympathetic nervous system is involved in the short-term regulation of subfoveal and parafoveal choroidal thickness, axial length and the morphology of the anterior sclera. The muscarinic blocker homatropine caused a significant subfoveal and parafoveal choroidal thickening, shortening of axial length, an enlargement of Schlemm's canal area and an increase in thickness of the conjunctival/episcleral complex. On the other hand, no notable changes in ocular parameters, except a decrease in the thickness of the conjunctival/episcleral tissues were found after instillation of the sympathomimetic drug phenylephrine.In an attempt to further improve our understanding of the myopigenic mechanisms influencing the thickness of the choroid in humans, we investigated the short-term influence of mixed interventions (positive and negative lens-imposed defocus / 2% homatropine) on choroidal thickness and axial length in emmetropic and myopic subjects. Homatropine prevented choroidal thinning in response to hyperopic defocus.This finding is consistent with the anti-myopia effects of muscarinic blockers and supports the potential importance of hyperopic defocus in the development of human myopia. By contrast, co-administration of homatropine with myopic defocus did not enhance the thicken...

show abstract

Sympathetic and parasympathetic pupillary dysfunction in familial dysautonomia

Cited by 26 publications

References 26 publications

Pupillometry in congenital central hypoventilation syndrome (CCHS): quantitative evidence of autonomic nervous system dysregulation

Pupillometry in congenital central hypoventilation syndrome (CCHS): quantitative evidence of autonomic nervous system dysregulation

Immediate effects of a thoracic spine thrust manipulation on the autonomic nervous system: a randomized clinical trial

The Influence of the Autonomic Nervous System on the Human Choroid

Contact Info

Product

Resources

About