The following is adapted from a case presented in the Journal of
the American Medical Association (JAMA).
JAMA (2019) "Dilated Pupil in a Patient with Hyperhidrosis"
322(3): 264-265. Quotes from the text of the paper
are presented in the yellow blocks; questions are presented in the
blue blocks.
A 39-year-old woman presented to the emergency department after she noticed that her left pupil was dilated when looking in the mirror earlier in the day.
Click on this link to the article and look at the right-hand side of the figure to see how the patient's eyes appeared.
What general type of neuron affects contraction of smooth
muscle in the iris to control pupil diameter?
What specific type of neuron causes dilation of the
pupil?
What specific type of neuron causes constriction of the
pupil?
She had a medical history of hypertension and palmar and axillary hyperhidrosis. She denied double vision, ptosis, headache, and weakness. On examination, she appeared well and her blood pressure was 128/78 mm Hg; heart rate, 76/min; and respiratory rate, 13/min. Visual acuity was 20/20 in both eyes, there was no ptosis, and extraocular movements were full. Pupillary examination revealed anisocoria...
Anisocoria is the term used to describe unequal pupil size. Anisocoria may be a sign of a serious neurological condition and so requires careful evaluation.
One possibility is injury to cranial nerves carrying the autonomic axons that control the size of the pupil. For instance, the occulomotor nerve (cranial nerve III) contains the parasympathetic preganglionic axons that control the pupil, but it also has axons of somatic motor neurons that innervate skeletal muscles responsible for eye movements and retraction of the eyelid. So an injury that disrupts the function of axons in the occulomotor nerve would cause abnormal control of eye movement and drooping of the eyelid, which is called ptosis. This patient had no double vision, normal control of eye movement ("extraocular movements were full") and no ptosis, indicating there was no problem with the occulomotor nerve.
...Anisocoria was more pronounced in bright lighting conditions. The right pupil measured 6 mm in the dark and 3 mm in the light, whereas the left pupil measured 9 mm in the dark and 8 mm in the light. The left pupil was poorly reactive to light and to a near target.
Examining the size of the pupils in both low light and bright light is a test that determines which pupil is the abnormal one. This test relies on pupillary light reflex. In this reflex, light detected in the eye activates the parasympathetic output to both pupils, causing them to constrict. In dim light, the sympathetic output to the eyes is activated, and the pupils will dilate. In this case, the left eye remained dilated in bright light, indicating that this was the abnormal pupil.
Evaluation of the pupillary response to light is a very important and useful neurological examination. An abnormal response can occur due to a problem in detecting light (the afferent pathway), the autonomic (efferent) output to the iris muscles, or in the midbrain nuclei where interneurons involved in the response are located.
The key to the correct diagnosis in this case is the presence of an isolated dilated pupil in a well-appearing patient with an otherwise normal neurologic examination...A detailed review of the patient’s medications was performed and it was discovered that she was using glycopyrronium bromide (glycopyrrolate), an anticholinergic medication.
Recall that this patient has a history of palmar and axillary hyperhidrosis. "Hyperhidrosis" means excessive sweating; "palmar" means from the palms and "axillary" means from the armpits. Hyperhidrosis may be treated with antiperspirants that block sweat ducts, but in more serious cases it can be treated with drugs that are receptor antagonists that block autonomic activation of the sweat glands, such as the glycopyrronium bromide that this patient was using. The patient probably inadvertently touched her left eye or nearby tissues after handling the drug, causing the problem with the left pupil.
The drug is blocking receptors on which type of muscle in the
iris, circular or radial?
Glycopyrronium bromide is an anticholinergic drug. What specific receptor type does this drug block?
The patient was informed that the dilated pupil was likely a result of the glycopyrronium bromide used for her hyperhidrosis. She temporarily discontinued the medication and her pupil returned to normal size after 5 days, confirming the diagnosis. At a follow-up appointment 2 weeks later, her pupils were both normal-sized and symmetric, and she continued to have no ptosis or extraocular dysmotility.
You may be thinking to yourself that sweating
is something that gets turned on during the fight-or-flight
response, in other words, by the sympathetic nervous
system. That is correct; and hyperhidrosis is thought to
occur due to excessive sympathetic activation of the sweat
glands. However, the drug this patient was using blocked
cholinergic neurotransmission, whereas sympathetic neurons
usually release the neurotransmitter norepinephrine. It
turns out that innervation of the sweat glands is an example
of an exception to the rule: in this case, the sympathetic
postganglionic neurons release acetylcholine instead of
norepinephrine, and the receptors on the sweat glands are
muscarinic receptors.
If you are interested in looking at the original paper, here is the citation:
Micieli, R, and Micieli, J.A. (2019) "Dilated Pupil in a
Patient with Hyperhidrosis" JAMA 322(3): 264-5 link
to article
Here is a link to an ad for Qbrexa, a product for treating hyperhidrosis that gained FDA approval in 2018.
I also found it interesting to look at patient reviews of the drug at this site.