Deficient Vascular Innervation in Familial Dysautonomia, an Explanation for Vasomotor Instability

Grover‐Johnson, Nicola; Pearson, John

doi:10.1111/j.1365-2990.1976.tb00498.x

Cited by 52 publications

(29 citation statements)

References 29 publications

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“…Orthostatic changes are consistent with an attenuated sympathetic response; supine plasma levels of norepinephrine (NE) are normal or elevated but fail to increase appropriately upon standing (10,12). Supine episodic hypertension may reflect denervation hypersensitivity; in the context of reduced sympathetic innervation of peripheral blood vessels, there is exaggerated vasoconstriction in response to small increases in NE (13,14).…”

Section: Discussionmentioning

confidence: 99%

Renal Transplantation in Familial Dysautonomia

Rekhtman¹,

Bomback²,

Nash³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: Chronic kidney disease (CKD) is an increasingly recognized complication of familial dysautonomia (FD), a neurodevelopmental disorder with protean systemic manifestations that are the result of sensory and autonomic dysfunction. Progressive renal dysfunction occurs due to chronic volume depletion and cardiovascular lability with supine hypertension and orthostatic hypotension. By age 25, nearly one-half of all patients with FD will have reached stage 3 CKD. Furthermore, dialysis for ESRD in FD patients is associated with multiple complications and poor outcomes.Design, settings, participants, & measurements: We report two patients with FD who developed ESRD at ages 27 and 16, respectively, and underwent renal transplantation. Transplant was performed after 3 months on intermittent hemodialysis (HD) in the first case and after 1 month on twice-weekly continuous veno-venous hemodialysis (CVVHD) in the second case.Results: Both patients tolerated surgery well and have maintained good graft function at 20 and 24 months posttransplantation, respectively. Symptomatic and functional improvements have included lower supine BP and increased sensitivity to antihypertensive agents.Conclusions: As general supportive care improves the lifespan of FD patients, issues related to the management of ESRD will become more important. Renal transplantation provides a viable alternative to dialysis for FD patients with ESRD.

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Section: Discussionmentioning

confidence: 99%

Renal Transplantation in Familial Dysautonomia

Rekhtman¹,

Bomback²,

Nash³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…A second, probably more important consequence of the myogenic quasi-rigidity of the vascular bed is a more efficient modulation by the neurogenic and neurohumoral (or metabolic) mechanisms that assure autoregulation in response to rapid BP fluctuations [6]. It is conceivable that stiffening of the resistance vessels with consecutive increase of the myogenic vessel rigidity furthers the effects of a reduced but remnant central sympathetic output or release of neurohumoral factors [1,3,6,[29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…While the ability to dilate correlates with the myogenic vessel rigidity, the rapid vasoconstriction is not primarily mediated by myogenic mechanisms, but depends more on neural and neurohumoral or metabolic components of cerebral autoregulation [5][6][7][8]. We assume that the reduced capacity to constrict resistance vessels is due to the sympathetic deficiency in FD patients [1,3,[29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Valsalva maneuver suggests increased rigidity of cerebral resistance vessels in familial dysautonomia

Hilz

Axelrod

Steingrueber

et al. 2002

Clinical Autonomic Research

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In familial dysautonomia (FD), cerebral autoregulation (CA) must adjust cerebral blood flow to extreme and rapid fluctuations in systemic blood pressure. Compromised CA during systemic blood pressure (BP) fluctuations might contribute to central autonomic dysfunction in FD. To evaluate CA during rapid BP changes, we monitored heart rate (HR), radial artery BP and middle cerebral artery blood flow velocity (CBFV), using transcranial Doppler sonography, in eight FD patients and twelve age-matched controls in supine position at baseline and during a Valsalva maneuver (VM, 40 mmHg expiratory pressure for 15 seconds). The best of four VM recordings was analyzed. We calculated two autoregulation parameters. CA(II) reflects BP related autoregulatory CBFV increase in late phase II of VM. CA(II) = [(CBFV(II late)-CBFV(II early))/CBFV(II early)]/[(BP(II late)-BP(II early))/BP(II early)]. CA(IV) reflects BP and HR related autoregulatory CBFV increase in phase IV of VM. CA(IV) = (CBFV(IV)/CBFV(I))/(BP(IV)/BP(I))/(HR(IV)/HR(I)). Baseline systemic BP, but not CBFV, was higher in the patients than the controls. During VM, both groups had similar CBFV and BP values, but CAIV and especially CA(II) were significantly lower in the patients than the controls. We have documented that FD patients maintain stable CBFV during rapid BP fluctuations associated with early and late phase II and phase IV of VM suggesting that small intracerebral vessels of FD patients are less responsive to rapid systemic blood pressure fluctuations. To compensate for decreased sympathetic vascular innervation, we propose that FD patients may alter the myogenic component of CA by vessel wall thickening resulting in increased rigidity of intracerebral resistance vessels. The resulting vasoconstriction would allow maintenance of normal baseline CBFV in spite of chronic recumbent hypertension.

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“…In FD patients, there is a depletion of neurons in the spinal cord intermedio-lateral gray columns. The size of sympathetic ganglia and the number of neurons as well as peripheral sympathetic nerve terminals are reduced [5,9,60].…”

Section: Sympathetic Skin Response In Familial Dysautonomia Patientsmentioning

confidence: 99%

Sympathetic skin response following thermal, electrical, acoustic, and inspiratory gasp stimulation in familial dysautonomia patients and healthy persons

Hilz

Azelrod

Schweibold

et al. 1999

Clinical Autonomic Research

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To determine whether sympathetic skin response (SSR) testing evaluates afferent small or efferent sympathetic nerve fiber dysfunction, we studied SSR in patients with familial dysautonomia (FD) in whom both afferent small and efferent sympathetic fibers are largely reduced. We analyzed whether the response pattern to a combination of stimuli specific for large or small fiber activation allows differentiation between afferent and efferent small fiber dysfunction. In 52 volunteers and 13 FD patients, SSR was studied at palms and soles after warm, cold and heat as well as electrical, acoustic, and inspiratory gasp stimulation. In addition, thermal thresholds were assessed at four body sites using a Thermotest device (Somedic; Stockholm, Sweden). In volunteers, any stimulus induced reproducible SSRs. Only cold failed to evoke SSR in two volunteers. In all FD patients, electrical SSR was present, but amplitudes were reduced. Five patients had no acoustic SSR, four had no inspiratory SSR. Thermal SSR was absent in 10 patients with abnormal thermal perception and present in one patient with preserved thermal sensation. In two patients, thermal SSR was present only when skin areas with preserved temperature perception were stimulated. In patients with FD, preserved electrical SSR demonstrated the overall integrity of the SSR reflex but amplitude reduction suggested impaired sudomotor activation. SSR responses were dependent on the perception of the stimulus. In the presence of preserved electrical SSR, absent thermal SSR reflects afferent small fiber dysfunction. A combination of SSR stimulus types allows differentiation between afferent small or efferent sympathetic nerve fiber dysfunction.

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Deficient Vascular Innervation in Familial Dysautonomia, an Explanation for Vasomotor Instability

Cited by 52 publications

References 29 publications

Renal Transplantation in Familial Dysautonomia

Renal Transplantation in Familial Dysautonomia

Valsalva maneuver suggests increased rigidity of cerebral resistance vessels in familial dysautonomia

Sympathetic skin response following thermal, electrical, acoustic, and inspiratory gasp stimulation in familial dysautonomia patients and healthy persons

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