BACKGROUND: Harlequin syndrome is a curious phenomenon in which one half of the 
face fails to flush during thermal or emotional stress as a result of damage to 
vasodilator sympathetic fibers. Anecdotal reports suggest that some of these 
patients have abnormal pupils. In this study we set out to systematically 
investigate autonomic pupil disturbances in an unselected cohort of patients 
with harlequin syndrome.
METHODS: A consecutive series of 39 patients with harlequin syndrome who were 
referred to a tertiary autonomic function laboratory underwent slit-lamp 
examinations, testing of deep tendon reflexes, infrared video pupillography and, 
where needed, additional pharmacologic pupillary testing. Results were compared 
with a meta-analysis of all previously reported cases of harlequin syndrome (n = 
39) identified from a literature search.
RESULTS: In 65% of patients, no underlying causative medical disturbance could 
be identified. In 64% of patients, there were abnormal pupils, most commonly 
Horner syndrome, which was always present ipsilateral to the side of the face 
with impaired facial sweating and flushing. The lesion was postganglionic in 9 
of 10 patients tested pharmacologically. Five (13%) patients had tonic pupils, 
most of whom also had tendon areflexia but no other neurologic findings, a 
pattern consistent with Holmes-Adie syndrome. In 2 of these patients, tonic and 
Horner pupils coexisted. Normal pupils were present in 36% of patients. These 
results are similar to those for the 39 previously reported patients with 
harlequin syndrome.
CONCLUSIONS: The frequent coexistence of harlequin and Horner syndromes without 
other neurologic deficits suggests pathologic changes affecting the superior 
cervical ganglion. Because either syndrome may occur alone, damage is apparently 
selective. Among the patients with harlequin syndrome who also have tonic pupils 
and tendon areflexia (Holmes-Adie syndrome), we postulate a ganglionopathy 
affecting not merely the (sympathetic) superior cervical ganglion, but also the 
(parasympathetic) ciliary and dorsal root ganglia. Because we found that more 
than 10% of patients had an undisclosed mass lesion in the chest or neck or a 
generalized autonomic neuropathy, we recommend a targeted evaluation in selected 
patients with harlequin syndrome.