Clin Auton Res (2011) 21:5556 DOI 10.

1007/s10286-010-0081-7

CASE REPORT

Holmes-Adie syndrome associated with high altitude pulmonary edema and low chemo-responsiveness to hypoxia
Jean-Paul Richalet Murielle Letournel Jeffrey Salama

Received: 31 March 2010 / Accepted: 2 August 2010 / Published online: 16 September 2010 Springer-Verlag 2010

Abstract A 63-year-old patient with Holmes-Adie syndrome presented an altered peripheral chemoreex and suffered from high altitude pulmonary edema, suggesting an alteration of sensitive afferent bers from the peripheral chemoreceptors. Chemo-responsiveness to hypoxia should be explored before any exposure to moderate altitude in Holmes-Adie patients.

A 63-year-old adult was admitted at the Bourg-Saint Maurice hospital in the French Alps for an acute episode of acute mountain sickness with headache, nausea, fatigue and insomnia, and high altitude pulmonary edema (HAPE), with severe dyspnea at rest and fatigue, that occurred on the second day after his arrival to Tignes, a ski resort located at 2,100 m altitude. In Tignes, pulse oximetry showed an arterial oxygen saturation of 71% on ambient air. The thorax X-ray performed at admittance in BourgSaint Maurice (840 m) showed interstitial edema in the basal part of the left lung. His clinical condition rapidly improved, with discharge from the hospital after 1 day.

J.-P. Richalet M. Letournel Service de Physiologie, Explorations Fonctionnelles et Medecine du Sport, AP-HP, Hopital Avicenne, 93009 Bobigny, France J.-P. Richalet (&) ` Laboratoire Reponses Cellulaires et Fonctionnelles a lHypoxie , EA2363, UFR SMBH, Universite Paris 13, 74 rue Marcel Cachin, 93017 Bobigny, France e-mail: richalet@smbh.univ-paris13.fr J. Salama Service de Neurologie, AP-HP, Hopital Avicenne, 93009 Bobigny, France

In the clinical history of the patient, we can notice a systemic hypertension treated by valsartan and hydrochlorothiazide. Further anamnesis evidenced the diagnosis of a Holmes-Adie syndrome evoked in 1992 in front of a tonic pupil and tendon areexia, without any other pathological manifestation. One year later, at Avicenne hospital in Bobigny (France), a neurological exam revealed an abolition of tendon reexes of the superior limbs (except for left tricipital) and inferior limbs, an abolition of pallaesthesia in the right inferior limb, below the knee. Right pupil was tonic and unresponsive to light. No dystrophy of bular nerve was observed, and cubital nerves were normal. The Romberg sign was positive. Neither cerebella dysfunction nor motor decit was observed. An electromyographic evaluation showed an axonal sensitive decit (normal latencies and very low amplitudes of sensitive potentials) without motor decit. These ndings are compatible with a diffuse axonal sensitive polyneuropathy. A hypoxic exercise tolerance test was performed at moderate intensity (50 W) and at the equivalent altitude of 4,800 m [1]. A severe drop in arterial oxygen saturation (ear oximetry) down to 49% was observed during the hypoxic exercise, with an absence of ventilatory response to hypoxia (Fig. 1), suggesting an abolition of peripheral chemosensitivity. To our knowledge, this is the rst report of altered chemoreex in a patient with Holmes-Adie syndrome. Main risk factors involved in the development of HAPE are hypoxia, exercise, pulmonary hypertension, obesity, and low ventilatory response to hypoxia [2]. In the present case, exercise and altitude exposure were moderate, neither cardiac malfunction nor pulmonary hypertension were observed at echocardiography and body mass index was 25.7 kg/m2. The only risk factor was a low chemo-responsiveness that could

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Clin Auton Res (2011) 21:5556

_ Fig. 1 Hypoxic exercise test. Ventilation (VE) and arterial oxygen saturation (SaO2) in a patient with Holmes-Adie syndrome (left) and in a normal control subject (right). Note the profound decrease in SaO2 during exercise in hypoxia in the patient, and the absence of change in ventilation at transition between hypoxic and normoxic

exercise (50 W) in the patient compared to a normal ventilatory response in the control subject (arrows). Hypoxic conditions were obtained by breathing a gas mixture with a FIO2 = 0.115 (equivalent to 4,800 m) (Ref: Richalet et al. [1])

be part of the autonomous nervous system dysfunctions frequently observed in Holmes-Adie syndrome. However, alterations previously observed concerned cardiovascular reexes, chronic cough, thermoregulatory, and sweating processes [35], but to our knowledge, no alteration of chemoreexes has been previously described. A similar alteration in ventilatory sensitivity to hypoxia has been described in patients with familial dysautonomia [6], associated with more severe autonomic dysfunctions, especially in the cardiovascular system, and a high mortality compared to Holmes-Adie syndrome. In conclusion, patients with Holmes-Adie syndrome may present an alteration in their peripheral chemoreex and are probably at risk of HAPE even at moderate altitude. Their chemo-responsiveness to hypoxia should be explored before any exposure to moderate ([2,000 m) altitude.
Conict of interest None.

References
1. Richalet JP, Gimenez-Roqueplo AP, Peyrard S, Venisse A, Marelle L, Burnichon N, Bouzamondo A, Jeunemaitre X, Azizi M, Elghozi JL (2009) A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia? Clin Auton Res 19:335342 2. Maggiorini M (2006) High altitude-induced pulmonary oedema. Cardiovasc Res 72:4150 3. Bacon PJ, Smith SE (1993) Cardiovascular and sweating dysfunction in patients with Holmes-Adie syndrome. J Neurol Neurosurg Psychiatry 56:10961102 4. Martinelli P (2000) Holmes-Adie syndrome. Lancet 356:17601761 5. Ford PA, Barnes PJ, Usmani OS (2007) Holmes-Adie syndrome chronic cough. Lancet 369:342 6. Bernardi L, Hilz M, Stemper B, Passino C, Welsch G, Axelrod FB (2003) Respiratory and cerebrovascular responses to hypoxia and hypercapnia in familial dysautonomia. Am J Respir Crit Care Med 167:141149

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