Adie Syndrome

Adie syndrome, also known as the Holmes-Adie syndrome, is a neurological disorder of unknown etiology comprising unilateral or bilateral tonically dilated pupils with light-near dissociation and tendon areflexia. This activity outlines the evaluation and management of Adie syndrome and highlights the role of the interprofessional team in treating patients with this condition.

Objectives:

• Review the potential etiologies of Adie syndrome that should be ruled out when Adie syndrome is present.
• Describe the pathophysiology of Adie syndrome.
• Outline the evaluation of Adie syndrome.
• Summarize the importance of collaboration and communication amongst interprofessional team members to enhance care coordination for patients with Adie syndrome.

Synonyms of Adie Syndrome

• Adie's Pupil
• Adie's Syndrome
• Adie's Tonic Pupil
• Holmes-Adie Syndrome
• tonic pupil syndrome

General Discussion

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. In most individuals, the cause is unknown (idiopathic), but Adie syndrome can occur as 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 a usually non progressive 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.

Signs & Symptoms

Typically, Adie syndrome may result in a change in the dilation of one of the pupils.

In general, the pupils get smaller or larger in response to changes in light. These changes happen very quickly to help humans see in different light conditions. If a person has Adie syndrome, the affected pupil does not do this correctly. The pupil may stay dilated, meaning that it is open wider than necessary in the presence of light.

The eye may be less responsive, even when doctors shine a bright light near the eye to test for a reaction.

The affected eye may not necessarily cause symptoms. However, some people may experience impaired vision. The vision may be blurry, for instance, or the person may have trouble with depth perception.

In other cases, symptoms such as light sensitivity or the presence of “light glares” within the field of vision may also occur.

The symptoms of Adie syndrome tend to affect just one of the eyes. However, they may eventually begin to affect both eyes.

In addition to symptoms in the eye, a person with Adie syndrome will also have sluggish or absent deep tendon reflexes. Deep tendon reflexes are automatic, involuntary responses of the muscles in response to stimuli. Examples include reflexes in the knee and Achilles tendon.

Some people may experience additional symptoms, including headaches, pain in the face, and mood swings.

In some cases, a person may experience changes in sweating, which can be either excessive or reduced. While the combinationTrusted Source of decreased sweating, absent reflexes, and poor pupil responses is technically known as Ross’s syndrome, some doctors may diagnose this as a variant of Adie syndrome.

The symptoms of Adie syndrome are typically not severe or debilitating, but the condition can disrupt daily life and usually requires treatment. Anyone experiencing these symptoms should see a doctor or ophthalmologist for a diagnosis.

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 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 survive. 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. Tumor, 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 were 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.

Affected Populations

Adie syndrome affects females more often than males by a ratio by some estimates of 2.6:1 for cases where the cause is unknown. Young adults usually between the ages of 25 to 45 are most commonly affected. The prevalence of Adie’s pupil (not the full syndrome) is approximately 2 people per 1,000 in the general population. The exact incidence or prevalence of Adie syndrome itself is unknown.

Related Disorders

Symptoms of the following disorders can be similar to those of Adie syndrome. Comparisons may be useful for a differential diagnosis:

Ross syndrome is a variant of Adie syndrome in which affected individuals experience an impaired ability to sweat normally (anhidrosis) in association with Adie pupil and loss of deep tendon reflexes. The inability to sweat properly may result in the body attempting to compensate, resulting in certain areas of the body sweating excessively. Affected individuals may experience heat intolerance due to the sweating abnormalities. More than 40 cases of Ross syndrome have been reported in the medical literature. The exact underlying cause of this disorder is unknown.

Argyll Robertson pupil is a condition in which the pupils are small and constrict poorly to light, but do react to accommodation. Argyll Robertson pupil is most commonly associated with syphilis, but may simply be a long-standing bilateral tonic pupil.

Many other conditions can cause the characteristic eye symptoms of Adie syndrome including paralysis of the third facial nerve (third nerve palsy), Guillain-Barre syndrome, Miller-Fisher syndrome, Charcot-Marie-Tooth disease, Parry-Romberg syndrome, diabetes, chronic alcoholism, botulism, sarcoidosis, multiple sclerosis, and multiple system atrophy.

Aside from diseases, many other factors can cause pupil dilation. Certain drugs can cause the pupil to dilate. For example, transdermal scopolamine is a drug for motion sickness which comes in the form of a patch. If a patient accidentally gets the product in his or her eye (e.g., not washing the hands when finished with the kit) this may cause a dilated pupil. Another common cause is contact to plants containing scopolamine such as angels trumpet or jimson weed. Other drugs can cause dilated pupils or a delay in the response of eye muscles to light and darkness.

In lesions of the dorsal midbrain a pupil disorder is seen that can be confused with a tonic pupil: Both pupils are slightly dilated, do not or very slowly react to light but to near focusing. However, the near response is in this case prompt and fast, not tonic. Even the re-dilation after near fixation is promptly and fast. Additionally, those patients are not able to perform a fast and correct upward movement of their eyes.

Diagnosis

An ophthalmologist can help diagnose the symptoms of Adie syndrome. However, correctly diagnosing rare diseases, such as Adie syndrome, can take time.

A diagnosis of Adie syndrome generally involves evaluating the person’s medical history and genetics. Doctors will use a physical exam to look for the typical symptoms of Adie syndrome, such as slow reflex responses or symptoms in the eye.

In some cases, doctors may recommend genetic testing to look for known associated traits.

Treatment

The type of treatment is likely to depend on the symptoms that a person with Adie syndrome is experiencing.

Doctors may recommend eye drops containing a medication such as pilocarpine (Salagen), which can help constrict a pupil that has become overly dilated. This constriction may help with symptoms such as light glare and depth perception.

Other people may need to use prescription glasses or get a change in their prescription to help adjust their vision and compensate for any vision loss.

Those with excessive sweating may need a procedure called a thoracic sympathectomy to treat the issue if they do not respond to medication.

Other symptoms, such as absent or slow reflexes, may be permanent.

Complications

Few complications arise from Adie syndrome outside of the symptoms themselves.

Research suggests that 80% Trusted Sourceof cases are unilateral, meaning that they only affect one eye. Therefore, only about 20%Trusted Source of cases involve both eyes to some degree. The involvement may also progress, meaning that it may start in one eye and slowly start to affect the other eye, as well.

The eyesight of a person with Adie syndrome may change, and many people will have to wear corrective lenses to compensate for changes in vision.

Outlook

The symptoms of Adie syndrome can be bothersome and disrupt daily life, but they are typically manageable.

Aside from diagnosing and treating any possible underlying conditions, the outlook for people with Adie syndrome is generally good.

The syndrome is not progressive and does not pose any major threat. It is not life threatening and does not typically cause disability.

Some symptoms may be progressive. For instance, the loss of tendon reflexes tends to progress, and this is permanent.

While the pupil of the affected eye is generally larger when the person is younger, the affected pupil may shrink as the person ages. Older people with Adie syndrome may have a much smaller pupil in their affected eye.

Summary

Adie syndrome is a rare neurological condition that causes symptoms in the eyes and the autonomic nervous system. The affected eye may be more dilated or open than normal, and it will be very slow to respond to light.

The person may also have very sluggish or absent deep tendon reflexes.

Although the symptoms of Adie syndrome can be annoying, they are typically manageable. Eye drops and eyeglasses can help manage symptoms in the eye. Other symptoms, such as the loss of deep tendon reflexes, are often permanent.

Anyone experiencing noticeable symptoms of the condition, such as one pupil that is larger than the other or changes in vision, should see a doctor for a diagnosis.