Adie Syndrome


Article Author:
Manbeer Sarao


Article Editor:
Sandeep Sharma


Editors In Chief:
Evelyn Metz
Julie Sewell
Aditya Arya


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
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Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/16/2019 10:29:16 PM

Introduction

Adie syndrome is also called the Holmes-Adie Syndrome (HAS). It is named after William John Adie, the British neurologist of Australian descent, and Sir Gordon Morgan Holmes, an Irish neurologist. They reported it in 1931. Earlier in 1881, Hughlings Jackson had described mydriasis with pupillary paralysis. In 1914, Oloff had shown that tonic pupils could be caused by factors other than syphilis.

Adie syndrome is a rare neurological disorder of unknown etiology comprising unilateral or bilateral tonically dilated pupils with near light dissociation and tendon areflexia. The symptoms result from autonomic disturbances, affecting vasomotor and sudomotor functions. It has a female preponderance with absent or reduced deep tendon reflexes. The patient tends to have progressive miosis, to bilaterality (4% each year) and progressive loss of deep tendon reflexes.[1]

Etiology

Adie syndrome is mostly idiopathic and may rarely be caused by local disorders within the orbit affecting the ciliary ganglion including infection (syphilis, varicella, human parvovirus (B19) infection, Lyme disease),[2][3] ischemia (lymphomatoid granulomatosis, migraine, giant cell arteritis),[4][5] autoimmune disorders (Sjogren syndrome, polyarteritis nodosa, sarcoidosis, amyloidosis, Guillain-Barre syndrome, Vogt-Koyanagi-Harada disease),[6][7] cardiovascular disorders (carotid dissection),[8][9] local or general anesthesia,[10] orbital or choroidal tumor,[11] orbital surgery or laser therapy,[12] orbital floor fracture,[13] paraneoplastic (Lambert-Eaton myasthenic syndrome, congenital neuroblastoma with Hirschsprung disease and central hypoventilation syndrome, anti-Hu antibodies).[14][15]

Epidemiology

The incidence of Adie syndrome is approximately 4.7/100,000 population/year with a prevalence of two cases/1000 population (approximately). Young adults usually between the ages of 25 to 45 (mean age of 32 years) are most commonly affected. There is a female predominance (2.6:1). Sporadic Adie syndrome is commonly reported with rare reports of familial association.[16] It is unilateral in 80% of the cases. The exact incidence and prevalence rates have not been reported.

Pathophysiology

Pupillary symptoms of Holmes-Adie syndrome result from infections causing inflammation and damage to the parasympathetic neurons in the ciliary body and iris which travel along with the oculomotor nerve to synapse at the ciliary ganglion. As a result of damage to the dorsal root ganglion of the spinal cord, many patients experience the problems with autonomic control of the body. Reinnervation and upregulation of the postsynaptic receptors after damage to the ciliary ganglion results in a condition called denervation supersensitivity. The number of axons devoted to the ciliary body is much larger as compared to the ones for the pupil. Most often due to aberrant reinnervation after an injury or insult, the fibers which were previously devoted to the ciliary body get diverted to the pupil (aberrant regeneration).[17] A tonic reaction with light-near dissociation of the pupils is caused by activation of the near response after aberrant regeneration. The quantity (the number of nerve cells) and the quality (reduced myelin sheath in the gray and white matter) of neurons in the thoracic and lumbar ganglia of the posterior root and the medial region of the spinal cord decreases in patients with Adie syndrome.

History and Physical

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 (Ross variant). The Achilles tendon reflex is most commonly affected. Other signs may include difficulty reading due to hyperopia (accommodative paresis), segmental palsy of the sphincter, photophobia, cholinergic supersensitivity of the denervated muscles, and cardiovascular abnormalities (orthostatic hypotension).

Evaluation

Examination

The Adie pupil has a hallmark strong and tonic response of the near reaction with a slow and sustained relaxation due to iris sphincter hypersensitivity to muscarinic receptor agonists (e.g., pilocarpine). Over time, the tonic pupil, which is usually larger than the uninvolved fellow eye, tends to become smaller (the "little old Adie" pupil). The little old Adie pupils can be diagnosed by the poor light reaction and the tonic near response. Approximately 20% of Adie pupils are bilateral with a 4% incidence of bilateral involvement per year. Anisocoria greater than 1 mm and the presence of sector palsy on slit-lamp examination help to differentiate Adie from mydriasis due to a general neuropathy.

Pharmacologic Testing

Adie's syndrome is a clinical diagnosis. Low-Dose pilocarpine (one-eighth to one-tenth percent) test may be useful to demonstrate the cholinergic denervation supersensitivity (80% prevalent) in the tonic pupil.[18][19] After the administration of the dilute pilocarpine, a more miotic response will be seen compared with the fellow eye.

Etiologic Evaluation

Systemic dysautonomia, syphilis, diabetes, chronic alcoholism, encephalitis, multiple sclerosis, peripheral nerve disease (for example, Charcot-Marie-Tooth), rare midbrain tumors, herpes zoster, and neurosarcoidosis need to be ruled out. CT and MRI scans may be useful in the diagnostic testing of focal hypoactive reflexes.

Treatment / Management

Most patients with an idiopathic Adie syndrome do not require any treatment. Patients with an underlying systemic cause should have treatment directed at their other autonomic neuropathies. The treatment for impairment of the eyes (due to accommodative paresis) is to prescribe reading glasses. Topical low-dose pilocarpine or physostigmine drops may be administered as a treatment as well as a diagnostic measure. For those failing conservative management with drug therapy, thoracic sympathectomy is the treatment of choice for diaphoresis.[20]

Differential Diagnosis

Systemic autonomic neuropathies like Ross and Harlequin syndromes can also affect the ciliary ganglion and produce the tonic pupil.[21] Ross syndrome is characterized by a triad of a tonic pupil, hyporeflexia, and segmental anhidrosis.[22][23] Harlequin syndrome is a rare disorder of sympathetic nervous system characterized by the unilateral decreased or absence of flushing and sweating, particularly in the face, neck, arm, and chest in response to heat, exercise, or emotional factors. Some patients (13% in one series) also have a tonic pupil, although a Horner syndrome is more common and may coexist with a tonic pupil.

Prognosis

Adie syndrome does not have a progressive course. It is not a life-threatening condition and does not cause disabilities. It is not associated with any mortality rate. The loss of deep tendon reflexes is permanent and may progress over time. Most patients require reassurance after confirmation of the diagnosis. There have been rare associations of angle-closure glaucoma with Adie pupil.[24][25] The accommodative paresis gets better spontaneously over time. The pupil light reaction becomes weaker over time with an increasing light-near dissociation, and the pupil becomes smaller with time ("little old Adie").

Enhancing Healthcare Team Outcomes

Care coordination by an interprofessional team of neurologists and ophthalmologists is needed for earlier detection and improvement in the care of the patient. The involvement of infectious disease and rheumatology specialists early on in the management of patients with tonic pupils can lead to a significant reduction in the time to diagnosis while ruling out other causes. Cardiovascular involvement in some patients requires the assistance of a cardiology team.


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Adie Syndrome - Questions

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Which of the following is not a feature of Adie pupil?



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Damage to which of the following can result in Adie pupil?



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Which is a common clinical sign of Adie syndrome?



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Which of the following statements about Adie syndrome is false?



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Which of the following supports the diagnosis of a dilated pupil from Holmes-Adie syndrome as opposed to pharmacologic mydriasis?



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A young woman is noted to have anisocoria. The enlarged pupil reacts slowly to light and accommodates slowly. Deep tendon reflexes also are absent along with diaphoresis. What is the most likely diagnosis?



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A 40-year-old patient presents with lack of response to light in the right eye and a right pupil that is tonically dilated but can respond to accommodation. What is the term for this?



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Adie Syndrome - References

References

Thompson HS, Adie's syndrome: some new observations. Transactions of the American Ophthalmological Society. 1977     [PubMed]
Leavitt JA,Wayman LL,Hodge DO,Brubaker RF, Pupillary response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil. American journal of ophthalmology. 2002 Mar     [PubMed]
Sakai T,Shikishima K,Mizobuchi T,Yoshida M,Kitahara K, Bilateral tonic pupils associated with neurosyphilis. Japanese journal of ophthalmology. 2003 Jul-Aug     [PubMed]
Bennett JL,Pelak VA,Mourelatos Z,Bird S,Galetta SL, Acute sensorimotor polyneuropathy with tonic pupils and an abduction deficit: an unusual presentation of polyarteritis nodosa. Survey of ophthalmology. 1999 Jan-Feb     [PubMed]
Foroozan R,Buono LM,Savino PJ,Sergott RC, Tonic pupils from giant cell arteritis. The British journal of ophthalmology. 2003 Apr     [PubMed]
Foster RE,Kosmorsky GS,Sweeney PJ,Masaryk TJ, Horner's syndrome secondary to spontaneous carotid dissection with normal angiographic findings. Archives of ophthalmology (Chicago, Ill. : 1960). 1991 Nov     [PubMed]
Goldstein SM,Liu GT,Edmond JC,Katowitz JA,Rorke LB, Orbital neural-glial hamartoma associated with a congenital tonic pupil. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus. 2002 Feb     [PubMed]
Jacobson DM, Pupillary responses to dilute pilocarpine in preganglionic 3rd nerve disorders. Neurology. 1990 May     [PubMed]
Kardon RH,Corbett JJ,Thompson HS, Segmental denervation and reinnervation of the iris sphincter as shown by infrared videographic transillumination. Ophthalmology. 1998 Feb     [PubMed]
Bruno MK,Winterkorn JM,Edgar MA,Kamal A,Stübgen JP, Unilateral Adie pupil as sole ophthalmic sign of anti-Hu paraneoplastic syndrome. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2000 Dec     [PubMed]
Patel JI,Jenkins L,Benjamin L,Webber S, Dilated pupils and loss of accommodation following diode panretinal photocoagulation with sub-tenon local anaesthetic in four cases. Eye (London, England). 2002 Sep     [PubMed]
Purvin VA, Adie's tonic pupil secondary to migraine. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 1995 Mar     [PubMed]
Serra Mitjans M,Callejas Pérez MA,Valls Solé J,Grimalt Santacana R,Rubio Garay M,Iglesias Sentís M, [Surgical treatment for compensatory hyperhidrosis in Adie syndrome]. Archivos de bronconeumologia. 2004 Feb     [PubMed]
Shin RK,Galetta SL,Ting TY,Armstrong K,Bird SJ, Ross syndrome plus: beyond horner, Holmes-Adie, and harlequin. Neurology. 2000 Dec 26     [PubMed]
Guaraldi P,Mathias CJ, Progression of cardiovascular autonomic dysfunction in Holmes-Adie syndrome. Journal of neurology, neurosurgery, and psychiatry. 2011 Sep     [PubMed]
Stromberg BV,Knibbe M, Anisocoria following reduction of bilateral orbital floor fractures. Annals of plastic surgery. 1988 Nov     [PubMed]
Weller M,Wilhelm H,Sommer N,Dichgans J,Wiethölter H, Tonic pupil, areflexia, and segmental anhidrosis: two additional cases of Ross syndrome and review of the literature. Journal of neurology. 1992 Apr     [PubMed]
Wirtz PW,de Keizer RJ,de Visser M,Wintzen AR,Verschuuren JJ, Tonic pupils in Lambert-Eaton myasthenic syndrome. Muscle     [PubMed]
Wolfe GI,Galetta SL,Teener JW,Katz JS,Bird SJ, Site of autonomic dysfunction in a patient with Ross' syndrome and postganglionic Horner's syndrome. Neurology. 1995 Nov     [PubMed]
Kobayashi M,Takenami T,Kimotsuki H,Mukuno K,Hoka S, Adie syndrome associated with general anesthesia. Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2008 Feb     [PubMed]
Kawana K,Okamoto F,Nose H,Oshika T, A case of angle closure glaucoma caused by plateau iris and adie's pupil. American journal of ophthalmology. 2003 May     [PubMed]
Leibovitch I,Kurtz S,Almog Y, Adie's tonic pupil-induced angle-closure glaucoma. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2002 Jan-Feb     [PubMed]
Stricker RB,Winger EE, Holmes-Adie syndrome and Lyme disease. Lancet (London, England). 2001 Mar 10     [PubMed]
Rudolf Gde M, Tonic Pupils with Absent Tendon Reflexes in Mother and Daughter. The Journal of neurology and psychopathology. 1936 Apr     [PubMed]
Garza Leon M,Herrera-Jimenez IP,González-Madrigal PM, Complete Vogt-Koyanagi-Harada disease and Holmes-Adie syndrome: case report. Ocular immunology and inflammation. 2014 Aug     [PubMed]

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