Adie syndrome, or Holmes-Adie syndrome, is a rare neurological disorder affecting the pupil of the eye. In most patients, the pupil is larger than normal (dilated) and slow to react in response to direct light. Absent or poor tendon reflexes are also associated with this disorder. The syndrome is caused by damage to the postganglionic fibers of the parasympathetic innervation of the eye, usually by a viral or bacterial infection that causes inflammation, and affects the pupil of the eye and the autonomic nervous system. It can occur due to other conditions such as trauma, surgery, lack of blood flow (ischemia), or infection. In rare cases, localized disturbance of sweat secretion is associated with Adie syndrome (Ross syndrome). Adie syndrome involves usually nonprogressive and limited damage to the autonomic nervous system, which is the portion of the nervous system that controls or regulates certain involuntary body functions including the reaction of the pupils to stimuli.
The term Adie syndrome is used when both abnormalities of the pupil and loss of deep tendon reflexes are present. However, these findings may not develop at the same time. When only abnormalities affecting the pupil are present, the disorder may be referred to as Adie’s pupil, Adie’s tonic pupil, or, most commonly, tonic pupil. When a person’s pupils are of unequal size, the term anisocoria may be used.
Causes
In most instances, the exact cause of Adie syndrome is unknown (idiopathic). It is believed that most cases result from inflammation or damage to the ciliary ganglion, a cluster of nerve cells found in the eye socket (orbit) just behind the eyes, or damage to the post-ganglionic nerves. The ciliary ganglion is part of the parasympathetic nervous system, which is itself part of the autonomic nervous system. The parasympathetic nervous system relaxes the body and inhibits or slows down high energy functions.
The ciliary ganglion supplies nerves (innervates) to the eye. These nerves carry signals that help to control the pupil’s response to stimuli such as growing smaller or larger in response to light, dark or other stimuli. These nerves communicate with the iris sphincter muscle, the muscle that controls how much light enters the pupil (causing the pupil to either contract or grow larger). However, most of the cells of the ciliary ganglion (97%) serve as accommodation and supply the ciliary muscle which adjusts the crystalline lens of the eye to near vision.
In Adie syndrome, both these nerve cells are damaged. Because there are so many nerve cells serving accommodation usually a sufficient amount survives. Therefore, accommodation difficulties are not obvious or less obvious. Eventually, the damaged nerves may regenerate, but some do so improperly (aberrant regeneration). Because the nerve cells serving the pupillary sphincter are very few it is unlikely that many of them regenerate and restore the pupillary light reflex. However, cells that supply the ciliary muscle may regenerate and innervate not only the ciliary muscle but also the pupillary sphincter muscle (aberrant regeneration). This explains why the near response in a tonic pupil is present but slow. It is being elicited by nerve cells that were designed for accommodation, a slower movement than pupillary constriction. In most instances, damage to the ciliary ganglion or the postganglionic nerves is believed to be caused by a viral infection. There is evidence that also autoimmune processes may play a role. Tumors, trauma, and inflammation (especially syphilis) have also been linked to Adie syndrome. The syndrome has also occurred as a complication of surgery to the area of the eye socket. It is also seen in giant cell arteritis, a severe vasculitis of the elderly. There are rare cases where a tonic pupil has occurred as a paraneoplastic disorder, but so far only in patients where the malignant disease already was known.
The loss of deep tendon reflexes is believed to be caused by damage to the dorsal root ganglions, a cluster of nerve cells in the root of spinal nerves.
Diagnosis
A diagnosis of Adie syndrome can be made by a thorough clinical evaluation and a detailed patient history. A complete eye examination by an ophthalmologist is recommended. An eye doctor may use water-downed (diluted) pilocarpine to test the pupil’s reaction. Pilocarpine, given in the form of eye drops, is a drug that causes the pupils to grow smaller (constrict). In individuals with Adie syndrome, the affected pupil, which does not constrict in response to light, will constrict in response to dilute pilocarpine (0.05 – 0.1%) to which a normal pupil would not constrict. If the pupil dilation is caused by contact with scopolamine or atropine, the pupil will not constrict even to higher concentrations (0.5 – 1%) which causes normal pupils to constrict vigorously.
Adie syndrome presents with at least one mydriatic pupil with poor or absent pupillary light reaction, tonic pupillary near response with light-near dissociation, decreased or loss of deep tendon reflexes, and abnormalities of sweating in Ross syndrome.[rx] The Achilles tendon reflex is most commonly affected. Patients may complain of difficulty in reading and photophobia. Other signs may include increased manifest hyperopia, anisometropia, segmental palsy of the sphincter, cholinergic supersensitivity of the denervated muscles, and cardiovascular abnormalities such as orthostatic hypotension.[rx][rx] Adie syndrome may also be associated with chronic coughing.[rx][rx]
In some patients with tonic pupils, constriction is observed when the conjunctiva is touched or irritated e.g. when grating onions.
An eye doctor may also compare the size of the affected eye versus the unaffected eye in darkness and light as well as evaluate the response of the pupil when focusing on an object close at hand.
An eye doctor may use a slit-lamp, a device that allows an eye doctor examines the eyes under high magnification, to detect segmental paralysis and a flattened border of the pupil so that the pupil appears irregularly shaped. In some instances, worm-like (vermiform) movements of the iris can be seen under slit-lamp examination. In most cases, the pupil seems slightly ‘ovally’ distorted.
Pharmacologic Testing
Adie’s syndrome is a clinical diagnosis. Low-concentration pilocarpine (one-eighth to one-tenth percent) test may be useful to demonstrate the cholinergic denervation supersensitivity (80% prevalent) in the tonic pupil.[rx][rx] After the administration of the dilute pilocarpine, a more miotic response will be seen in the affected eye compared with the normal fellow eye since these low concentrations are usually ineffective in normal pupils. Some pupils in third nerve palsy, however, also respond to 0.1% pilocarpine, and therefore, the diagnosis of an Adie pupil should not be based on pharmacologic testing of pupils alone.[rx]
Sweat Testing
Other tests that can be used to exclude Ross or harlequin syndromes include the starch iodine test and the spoon test which help in the detection of anhidrosis.[rx][rx]
Etiologic Evaluation
Conditions that could mimic or cause Adie syndrome include systemic dysautonomia, syphilis, diabetes, chronic alcoholism, encephalitis, multiple sclerosis, and peripheral nerve disease (for example, Charcot-Marie-Tooth), rare midbrain tumors, herpes zoster, and neurosarcoidosis should be ruled out. However, the specific workup for each patient will depend on the associated manifestations. Computed tomography and magnetic resonance imaging scans may be useful in the diagnostic testing of focal hypoactive reflexes.
Treatment
In most instances, treatment will not be necessary. Glasses may be prescribed to correct blurred vision; sunglasses can help individuals with sensitivity to light. Therapy using dilute pilocarpine may improve poor depth perception and relieve glare in some patients. The loss of deep tendon reflexes is permanent.
The usual treatment of a standardized Adie syndrome is to prescribe reading glasses to correct for impairment of the eye(s). Pilocarpine and physostigmine drops may be administered as a treatment as well as a diagnostic measure. Thoracic sympathectomy is the definitive treatment of diaphoresis if the condition is not treatable by drug therapy.[rx]
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