Clinical Neurology and Neurosurgery 101 (1999) 196 – 198
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Case report

Ondine’s curse in association with diabetes insipidus following
transient vertebrobasilar ischemia
J. Kraus *, J.G. Heckmann, A. Druschky, F. Erbguth, B. Neundörfer
Department of Neurology, Friedrich – Alexander–Uni6ersität Erlangen – Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany
Received 15 December 1998; received in revised form 2 February 1999; accepted 22 March 1999

Abstract
Ischemic lesions of the brainstem can lead to complex neurologic deficits. Failure of the automatic control of ventilation
(Ondine’s curse syndrome) is a possible but rare syndrome following localized brainstem dysfunction. We report on a 49-year-old
man with intermittent bradycardia, cranial nerves’ dysfunctions and a slight right-sided hemiparesis. An acute brainstem ischemia
was diagnosed and treated immediately with high-dose heparin. Cerebral angiography revealed a proximal occlusion of the left
vertebral artery but a normal right vertebral artery and a hyperplastic right posterior inferior cerebellar artery. Cranial Computed
Tomography and MRI scan demonstrated multiple ischemic lesions in the posterior circulation. During a 4-week treatment course
the patient underwent six episodes of acute severe hypoxia and hypercapnia requiring orotracheal intubation twice and manual
ventilation by air mask over a few minutes for four times after a tracheostomy had been performed. Twice a short-term episode
of hypothalamic Diabetes insipidus was observed following hypoventilation. We conclude that both Ondine’s curse syndrome and
diabetes insipidus were due to transient vertebrobasilar ischemia. © 1999 Elsevier Science B.V. All rights reserved.
Keywords: Ondine’s curse syndrome; Stroke; Brainstem infarction; Diabetes insipidus; Respiratory centers

1. Introduction
Ondine’s curse syndrome is described as failure of
automatic control of ventilation when mechanical ventilation disorders are excluded. This rare central alveolar hypoventilation disorder can appear both as
congenital and acquired disease [1,2]. The acquired
form of Ondine’s curse syndrome can be associated
with numerous pathological conditions such as multiple
sclerosis [3], Shy–Drager syndrome [4], infectious diseases like viral [5] and bacterial encephalitis [6], vascular malformation [7] and generalized anoxia-ischemia
[8]. A prominent coincidence has been found between
this syndrome and Hirschsprung’s disease, which is due
to segmental colonic aganglionosis [9,10]. However,
failure of automatic control of ventilation is rarely
reported following brainstem infarction and verte* Corresponding author. Present address: Department of Neurology, Justus – Liebig – Universität Gießen, Am Steg 10, 35385 Gießen,
Germany. Tel.: +49-641-9945400; fax: +49-641-9945449.

brobasilar ischemia in adults [11–13].
In literature Ondine’s curse in association with diabetes insipidus in adults is well known following tuberculosis and Shy–Drager syndrome but none of them
was combined with cerebral infarction [4,14]. We recently cared for a patient suffering from acute brainstem infarction in combination with Ondine’s curse
syndrome and central diabetes insipidus.

2. Case report
The 49-year-old male patient was admitted suffering
from intermittent bradycardia with heart rates down to
35 bpm, acute dysphagia, dysarthria, left-sided facial
sensory deficit and a slight right-sided hemiparesis.
These signs and symptoms led to the diagnosis ‘acute
brainstem ischemia’ and high-dose heparin treatment
was initiated.

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J. Kraus et al. / Clinical Neurology and Neurosurgery 101 (1999) 196–198

Because of his cardiac problems and fluctuating
brainstem symptoms the patient was transferred to the
intensive care unit 2 days later. On admission the
patient was awake, well orientated. The neurological
examination revealed nystagmus to the left and the
right lateral gaze with a vertical component, pupils’
anisocoria (right\ left), left-sided reduced cornea
reflex, facial sensory deficit on the left side, dysphagia
and dysarthria, slight flaccid left-sided hemiparesis,
hemiataxia and hemihypalgesia on the right side.
Cerebral angiography (Fig. 1) as well as Doppler’s
sonography demonstrated a proximal occlusion of the
left vertebral artery. The right vertebral artery was
normally filled and the right posterior inferior cerebellar artery (PICA) was found to be hyperplastic. However, the connection from the right vertebral artery to
the basilar artery was hypoplastic. There was no affection of the basilar artery. Cranial Computed Tomography showed slight hypodense lesions in both thalamus
regions, both occipital lobes and in the left cerebral
pedunculus. MRI scan additionally revealed infarction

197

of the left cerebellum as well as pontine and medullar
ischemic lesions on both sides.
After a temporary stabilization the patient had an
acute respiratory arrest which led to an emergency
orotracheal intubation followed by respirator therapy.
The patient could be extubated without any problems
after 9 days of respirator treatment. Ten hours later,
the sleeping patient suddenly stopped breathing again
and a new orotracheal intubation was necessary following blood gas study with PaO2 of 56.7 mmHg, oxygen
saturation of 83.4% and PaCO2 of 68.5 mmHg. Respirator therapy was necessary for another 2 days. The
subsequent pulmonary test was normal.
A tracheostomy was performed because of the two
attacks and several blood gas tests with hypoxia and
hypercapnia. In the further course of treatment another
four episodes of respiratory arrests requested manual
ventilation by an air mask. In addition, two episodes
with diagnosed central diabetes insipidus were treated
with vasopressin for several days.
Finally, the patient was stabilized after 4 weeks of
intensive care treatment and could be transferred to a
rehabilitation center. The follow-up examination after 6
months revealed discrete dysphagia and dysarthria, leftsided spastic hemiparesis so that the patient was only
ambulatory with assistance. The tracheostomy was
closed because the patient did not have any more
hypoventilation attacks.
3. Discussion

Fig. 1. Cerebral angiography of a 49-year-old patient: proximal
occlusion of the left vertebral artery, normal right vertebral artery
and hyperplastic right PICA; the connection from the right vertebral
artery to the basilar artery is hypoplastic.

In our patient acquired Ondine’s curse syndrome was
diagnosed based on six episodes with isolated respiratory arrest with hypoxia and hypercapnia but without a
mechanical ventilation failure. Ondine’s curse syndrome
is described in many clinical situations like multiple
sclerosis, Shy–Drager syndrome, encephalitis, vascular
malformation, generalized anoxia-ischemia and very
rarely in vertebrobasilar ischemia in adults [3–5,7–
9,11].
For three reasons the described case is unusual:
Firstly, the etiological aspect with ischemia of the
posterior circulation is very rare [11–13]. There are
only a few reports in literature describing brainstem
infarction as the cause of Ondine’s curse syndrome.
The severe vertebrobasilar arteriosclerosis in our patient led to multiple ischemic lesions of the brainstem
and the posterior circulation. Thus, the pathogenetic
concept of Ondine’s curse syndrome is hypoperfusion
of the brainstem and in particular of the respiratory
centers. The course with six isolated apnea attacks
with complete remission with stable ventilation for 6
months is atypical. It can be assumed that complete
occlusion of the left vertebral artery appeared accidentally. The small connection of the hypoplastic
distal vertebral artery on the right side might also be

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J. Kraus et al. / Clinical Neurology and Neurosurgery 101 (1999) 196–198

responsible for hypoperfusion in the more distal part of
the vertebrobasilar system. The consequences were cranial nerve dysfunctions and left-sided hemiparesis as
signs of brainstem infarction and as transient ischemic
attacks (TIA) of the brainstem with symptoms of Ondine’s curse syndrome. When perfusion of the brainstem
was improved by anticoagulant treatment, potential
spontaneous thrombolysis and revascularization including collateralization, the attacks of alveolar hypoventilation disappeared.
Secondly, our patient developed the combination of
Ondine’s curse syndrome with central diabetes insipidus. To our knowledge there is no report in the
literature of a combination of both diseases attributed
to vertebrobasilar ischemia. We consider that transient
diabetes insipidus can be regarded to hypothalamic
TIA as the condition appeared in two short-term
episodes and was completely reversible. Central diabetes insipidus following hypothalamic infarction or
other lesions is well known as thalamus and hypothalamus are supplied by perforant arteries from the posterior cerebral artery [15,16].
Thirdly, it is atypical that both syndromes are completely reversible. It may be speculated that recovery
occurred after increased perfusion of the brainstem by
improved vascularization, collateralization and anticoagulant therapy. Another possible explanation for this
positive course of the disease might be that the function
of affected respiratory centers of the lower brainstem
has been taken over by different structures, a phenomenon known as cerebral plasticity [17,18]. In addition, the positive outcome in our patient might be a
consequence of anatomical variations in the brainstem’s
functional architecture as well as in its vascular supply.
Cerebral angiography revealed a known anatomical
variation of the vertebrobasilar system in our patient
[19]. PICA has been found to be hyperplastic in combination with a hypoplastic or even absent connection
from the vertebral artery to the basilar artery on the
same side.
In conclusion when caring for patients with vertebrobasilar ischemia Ondine’s curse should be considered as a possible clinical condition.
Probably, the bilaterality of the brainstem lesions as
seen in MRI scan might be responsible for the occurrence and severity of Ondine’s curse syndrome in our
patient [8,20,21].
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