Quantitative studies of dorsal root ganglia and neuropathologic observations on spinal cords in familial dysautonomia

Pearson, John; Pytel, B; Grover‐Johnson, Nicola; Axelrod, Felicia B.; Dancis, Joseph

doi:10.1016/0022-510x(78)90103-x

Cited by 136 publications

(94 citation statements)

References 15 publications

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“…Neuropathological findings of the disease include brainstem, pontine, medullary, and spinal atrophy with neuronal depletion in dorsal root (sensory) and sympathetic ganglia, as well as reduced numbers of small myelinated and nonmyelinated (sensory) axons of peripheral nerves (8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Mendoza‐Santiesteban

Palma

Hedges

et al. 2017

Journal of Neuropathology &Amp; Experimental Neurology

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Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition.

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Section: Introductionmentioning

confidence: 99%

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Mendoza‐Santiesteban

Palma

Hedges

et al. 2017

Journal of Neuropathology &Amp; Experimental Neurology

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“…Interestingly, the patients also had postural hypotension and did not complain of pain when their feet were immersed in ice-cold water. Neuropathology studies in samples from patients with FD showed reduced number of primary sensory neurons in dorsal root ganglia 4 and fiber loss in spinothalamic and spinocerebellar tracts as well as in posterior columns of the spinal cord. 5 These findings provided an explanation for the impaired pain and temperature perception as well as the characteristic decreased/absent myotatic reflexes and gait ataxia.…”

Section: Discussionmentioning

confidence: 99%

Afferent baroreflex failure in familial dysautonomia

Kaufmann

Axelrod²,

Kaufmann³

2010

Neurology

106

102

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“…34 However, absence of REM sleep may also be due to brain pathology described in FD patients. [11][12][13][14][15][16][17] The scarce autopsies of FD patients showed spongiform degeneration of the reticular formation, particularly in the medulla, pons, and mesencephalon, but also pathology in other brain regions including the cerebellum or frontal and parietal lobes.…”

Section: Central Pathology May Compromise Onset Of Rem Sleep In Fd Pamentioning

confidence: 99%

“…5 While obstructive apneas can be treated with continuous positive airway pressure (CPAP), this treatment is less successful in central sleep apneas. 9,10 In FD patients, the pathology with central and peripheral autonomic dysfunction, 2,4,[11][12][13][14][15][16][17][18][19] kyphoscoliosis, 20 and craniofacial abnormalities 21 may give rise to both central and obstructive sleep apneas.…”

Section: Introductionmentioning

confidence: 99%

Obstructive Sleep-Disordered Breathing Is More Common than Central in Mild Familial Dysautonomia

Hilz

Moeller

Buechner

et al. 2016

Journal of Clinical Sleep Medicine

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Study Objectives:In familial dysautonomia (FD) patients, sleep-disordered breathing (SDB) might contribute to their high risk of sleep-related sudden death. Prevalence of central versus obstructive sleep apneas is controversial but may be therapeutically relevant. We, therefore, assessed sleep structure and SDB in FD-patients with no history of SDB. Methods: 11 mildly affected FD-patients (28 ± 11 years) without clinically overt SDB and 13 controls (28 ± 10 years) underwent polysomnographic recording during one night. We assessed sleep stages, obstructive and central apneas (≥ 90% air flow reduction) and hypopneas (> 30% decrease in airflow with ≥ 4% oxygen-desaturation), and determined obstructive (oAI) and central (cAI) apnea indices and the hypopnea index (HI) as count of respective apneas/hypopneas divided by sleep time. We obtained the apnea-hypopnea index (AHI4%) from the total of apneas and hypopneas divided by sleep time. We determined differences between FD-patients and controls using the U-test and within-group differences between oAIs, cAIs, and HIs using the Friedman test and Wilcoxon test. Results: Sleep structure was similar in FD-patients and controls. AHI4% and HI were significantly higher in patients than controls. In patients, HIs were higher than oAIs and oAIs were higher than cAIs. In controls, there was no difference between HIs, oAIs, and cAIs. Only patients had apneas and hypopneas during slow wave sleep. Conclusions: In our FD-patients, obstructive apneas were more common than central apneas. These findings may be related to FD-specific pathophysiology. The potential ramifications of SDB in FD-patients suggest the utility of polysomnography to unveil SDB and initiate treatment. Commentary: A commentary on this article appears in this issue on page 1583. Keywords: familial dysautonomia, hereditary sensory and autonomic neuropathy type III, obstructive sleep apnea, sleep-disordered breathing Citation: Hilz MJ, Moeller S, Buechner S, Czarkowska H, Ayappa I, Axelrod FB, Rapoport DM. Obstructive sleep-disordered breathing is more common than central in mild familial dysautonomia.

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Quantitative studies of dorsal root ganglia and neuropathologic observations on spinal cords in familial dysautonomia

Cited by 136 publications

References 15 publications

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Afferent baroreflex failure in familial dysautonomia

Obstructive Sleep-Disordered Breathing Is More Common than Central in Mild Familial Dysautonomia

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