WikiDoc Resources for Adie syndrome
Evidence Based Medicine
Guidelines / Policies / Govt
Patient Resources / Community
Healthcare Provider Resources
Continuing Medical Education (CME)
Experimental / Informatics
Editor-In-Chief: C. Michael Gibson, M.S., M.D.  Associate Editor(s)-in-Chief: Ahmad Muneeb, MBBS Synonyms and Keywords: Holmes-Adie Syndrome; Syndrome, Holmes-Adie; Syndrome, Adie's; Syndrome, Adie; Poorly Reacting Pupil; Holmes Adie Syndrome; Pupil, Poorly Reacting; Adie's Syndrome; Poorly Reacting Pupils; Pupils, Poorly Reacting
Adie syndrome is characterized by abnormal pupillary function and loss of deep tendon reflexes. Abnormal pupillary functioning in adie syndrome consists of poor pupillary response to light but a better near response (light near dissociation). Damage to ciliary ganglion is responsible for pupillary abnormalities while the loss of deep tendon reflexes is caused by damage to dorsal root ganglion of spinal cord. Most of the times the cause of Adie syndrome is unknown, however, multiple pathologies can cause adie syndrome. It is a benign condition and is mostly diagnosed clinically. Management is mostly symptom directed and depends upon the underlying etiology
- [[Adie] syndrome]] was first discovered by William John Adie, a British neurologist, and Sir Gordon Morgan Holmes, an Irish neurologist in 1931. This syndrome was named after these 2 neurologists. 
- Adie syndrome has a variant known as Ross syndrome, characterized by a triad of abnormal pupillary function, loss of deep tendon reflexes and sweating abnormalities. 
- The pathogenesis of adie syndrome is characterized by damage to ciliary ganglion and dorsal root ganglion of spinal cord. Ciliary ganglion provides innervation to iris and ciliary muscle, thus controlling pupillary function and accommodation. Ciliary ganglion neurons responsible for accommodation are in a much greater number than the neurons controlling pupillary function. In adie syndrome, neurons/nerve fibers controlling both accommodation and pupillary function are damaged. But because of the large no. of neruons, accommodation is unaffected or minimally affected in adie syndrome. Some of the damaged nerve fibers start to regenerate. As nerve fibers innervating pupillary sphincter muscle are less in no. so very few of these fibers regenerate and are insufficient to restore the normal pupillary function. On the other hand, nerve fibers to the ciliary muscle also regenerate but may do so in an inappropriate fashion, providing innervation to pupillary sphincter muscle along with ciliary muscle. As the pupillary sphincter muscle is now innervated by fibers originally responsible for accommodation(which is a slower process than pupillary light reaction) so pupillary light response is impaired. 
- Loss of deep tendon reflexes in adie syndrome is caused by damage to dorsal root ganglion of spinal cord. 
- On microscopic histopathological analysis, degeneration of ciliary ganglion and atrophy of sphincter pupillae muscle, are characteristic findings of adie syndrome. Other findings associated with adie syndrome include degenration of sacral dorsal root ganglion, superior cervical ganglion and sciatic nerve. 
Most commonly the cause of Adie syndrome is unknown(idiopathic). Less common causes of adie syndrome include infections like HIV, syphilis, varicella, lyme's disease, Human parvovirus-B19, autoimmune diseases like amyloidosis, sarcoidosis, guillain-barre syndrome, sjogren syndrome, polyarterities nodosa, vogt-koyanagi-haraga disease, ischemia caused by giant cell arteritis, migraine, lymphatoid granulomatosis, neuromuscular diseases like Lambert eaten syndrome, tumors affecting the orbit or choroid, orbital surgery, cardiovascular diseases, general anesthesia. ,anti-hu antibody.
Differentiating adie syndrome from other Diseases
- Adie syndrome must be differentiated from other diseases that cause light near dissocation or miosis, or mydriasis, such as:
Epidemiology and Demographics
- The prevalence of adie syndrome is approximately 2 per 1000 individuals. 
- The annual incidence of adie syndrome is estimated to be [4.7] cases per 100,000 individuals. 
- There is no racial predilection for adie syndrome.
- Common risk factors in the development of adie syndrome are infections, trauma, tumors, ischemia and autoimmune disorders.
Natural History, Complications and Prognosis
- Early clinical features include accommodative paresis, impaired light reflex and loss of deep tendon reflexes. Accomodative paresis tends to improve overtime, however, impairment of pupillary light reaction and deep tendon reflexes is persistent and in some cases may worsen overtime. 
- Complications of adie syndrome include angle closure glaucoma and amblyopia. However, they occur very rarely.
- Prognosis is generally good. Adie syndrome has no associated mortality rate as it is a nonlife-threatening condition. 
- The diagnosis of [[adie syndrome] is made when both pupillary abnormalities and absence or impairment of deep tendon reflexes are present. Although, both of these features may not coexist. If only pupillary abnormalities are present then the condition is referred to as adie pupil. 
History and Symptoms
- absent or impaired pupillary light reflex
- absent deep tendon reflexes (most commonly achilles tendon is involved).
- Tonic near response of pupil with Light near dissociation.
- Segmental palsy of sphincter
- Irregular shape of pupil
- orthostatic hypotension
- hypersensitivity to cholinergic agonists
- There are no specific laboratory findings associated with adie syndrome.
There are no ECG findings associated with adie syndrome.
There are no x-ray findings associated with adie syndrome.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with adie syndrome.
There are no CT scan findings associated with adie syndrome.
There are no MRI findings associated with adie syndrome.
Other Imaging Findings
There are no other imaging findings associated with adie syndrome.
Other Diagnostic Studies
Low dose pilocarpine test may be helpful in the diagnosis of adie syndrome. Finding suggestive of adie pupil includes an exaggerated miotic reaction of the affected pupil as compared to the normal pupil. This exaggerated response to low dose pilocarpine occurs as a consequence of cholinergic denervation hypersensitivity of the affected pupil. Normal pupils do not respond to such low doses of pilocarpine. To rule out Ross syndrome, sweating abnormalities can be checked by using starch iodine test and spoon test. 
- There is no treatment required for idiopathic adie syndrome. If any etiology is found, treatment should be directed against that etiology. Topical low dose pilocarpine or physostigmine can be used in symptomatic patients. For patients with accommodative paresis reading glasses should be prescribed.
- There are no primary preventive measures available for adie syndrome.
- Thompson HS (1977). "Adie's syndrome: some new observations". Transactions of the American Ophthalmological Society. 75: 587–626. PMC 1311565. PMID 613531.
- "Adie Syndrome - NORD (National Organization for Rare Disorders)".
- Sarao MS, Elnahry AG, Sharma S. "Adie Syndrome (Tonic Pupil Syndrome) Article - StatPearls".
- Agbeja AM, Dutton GN (1987). "Adie's syndrome as a cause of amblyopia". Journal of Pediatric Ophthalmology and Strabismus. 24 (4): 176–7. PMID 3668764.
- Cerny R, Rozsypal H, Kozner P, Machala L (October 2010). "Bilateral Holmes-Adie syndrome as an early manifestation of the HIV neuropathy". Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 31 (5): 661–3. doi:10.1007/s10072-010-0355-9. PMID 20567990.
- Sakai T, Shikishima K, Mizobuchi T, Yoshida M, Kitahara K (2003). "Bilateral tonic pupils associated with neurosyphilis". Japanese Journal of Ophthalmology. 47 (4): 368–71. doi:10.1016/s0021-5155(03)00058-3. PMID 12842205.
- Stricker RB, Winger EE (March 2001). "Holmes-Adie syndrome and Lyme disease". Lancet (London, England). 357 (9258): 805. doi:10.1016/S0140-6736(05)71234-4. PMID 11254002.
- Bennett JL, Pelak VA, Mourelatos Z, Bird S, Galetta SL (1999). "Acute sensorimotor polyneuropathy with tonic pupils and an abduction deficit: an unusual presentation of polyarteritis nodosa". Survey of Ophthalmology. 43 (4): 341–4. doi:10.1016/s0039-6257(98)00047-2. PMID 10025516.
- Garza Leon M, Herrera-Jimenez IP, González-Madrigal PM (August 2014). "Complete Vogt-Koyanagi-Harada disease and Holmes-Adie syndrome: case report". Ocular Immunology and Inflammation. 22 (4): 336–40. doi:10.3109/09273948.2013.848906. PMID 24215593.
- Foroozan R, Buono LM, Savino PJ, Sergott RC (April 2003). "Tonic pupils from giant cell arteritis". The British Journal of Ophthalmology. 87 (4): 510–2. doi:10.1136/bjo.87.4.510. PMC 1771609. PMID 12642330.
- Purvin VA (March 1995). "Adie's tonic pupil secondary to migraine". Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 15 (1): 43–4. PMID 7780572.
- Wirtz PW, de Keizer RJ, de Visser M, Wintzen AR, Verschuuren JJ (March 2001). "Tonic pupils in Lambert-Eaton myasthenic syndrome". Muscle & Nerve. 24 (3): 444–5. doi:10.1002/1097-4598(200103)24:3<444::aid-mus1021>3.0.co;2-w. PMID 11353435.
- Goldstein SM, Liu GT, Edmond JC, Katowitz JA, Rorke LB (February 2002). "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. 6 (1): 54–5. doi:10.1067/mpa.2002.120171. PMID 11907481.
- Stromberg BV, Knibbe M (November 1988). "Anisocoria following reduction of bilateral orbital floor fractures". Annals of Plastic Surgery. 21 (5): 486–8. doi:10.1097/00000637-198811000-00016. PMID 3232939.
- Guaraldi P, Mathias CJ (September 2011). "Progression of cardiovascular autonomic dysfunction in Holmes-Adie syndrome". Journal of Neurology, Neurosurgery, and Psychiatry. 82 (9): 1046–9. doi:10.1136/jnnp.2009.195917. PMID 20562402.
- Kobayashi M, Takenami T, Kimotsuki H, Mukuno K, Hoka S (February 2008). "Adie syndrome associated with general anesthesia". Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 55 (2): 130–1. doi:10.1007/BF03016329. PMID 18245077.
- Zhang L, Luo S, Jin H, Lv X, Chen J (2019). "Anti-Hu Antibody-Associated Adie's Pupil and Paraneoplastic Sensorimotor Polyneuropathy Caused by Primary Mediastinal Small Cell Carcinoma". Frontiers in Neurology. 10: 1236. doi:10.3389/fneur.2019.01236. PMC 6901962 Check
|pmc=value (help). PMID 31849812.
- Thompson HS, Kardon RH (June 2006). "The Argyll Robertson pupil". Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 26 (2): 134–8. doi:10.1097/01.wno.0000222971.09745.91. PMID 16845316.
- Shin RK, Galetta SL, Ting TY, Armstrong K, Bird SJ (December 2000). "Ross syndrome plus: beyond horner, Holmes-Adie, and harlequin". Neurology. 55 (12): 1841–6. doi:10.1212/wnl.55.12.1841. PMID 11134383.
- Martin TJ (February 2018). "Horner Syndrome: A Clinical Review". ACS Chemical Neuroscience. 9 (2): 177–186. doi:10.1021/acschemneuro.7b00405. PMID 29260849.
- Leibovitch I, Kurtz S, Almog Y (2002). "Adie's tonic pupil-induced angle-closure glaucoma". Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 216 (1): 71–2. doi:10.1159/000048302. PMID 11901294.
- Wilhelm H (September 1998). "Neuro-ophthalmology of pupillary function--practical guidelines". Journal of Neurology. 245 (9): 573–83. doi:10.1007/s004150050248. PMID 9758294.
- Emond D, Lebel M (September 2002). "Orthostatic hypotension and Holmes-Adie syndrome. Usefulness of the Valsalva ratio in the evaluation of baroreceptor dysfunction". Journal of Human Hypertension. 16 (9): 661–2. doi:10.1038/sj.jhh.1001455. PMID 12214264.
- Leavitt JA, Wayman LL, Hodge DO, Brubaker RF (March 2002). "Pupillary response to four concentrations of pilocarpine in normal subjects: application to testing for Adie tonic pupil". American Journal of Ophthalmology. 133 (3): 333–6. doi:10.1016/s0002-9394(01)01420-9. PMID 11860969.
- Ballestero-Díez M, García-Río I, Daudén E, Corrales-Arroyo M, García-Díez A (November 2005). "Ross syndrome, an entity included within the spectrum of partial disautonomic syndromes". Journal of the European Academy of Dermatology and Venereology : JEADV. 19 (6): 729–31. doi:10.1111/j.1468-3083.2005.01254.x. PMID 16268880.
- "Holmes-Adie Syndrome Information Page | National Institute of Neurological Disorders and Stroke".
- Serra Mitjans M, Callejas Pérez MA, Valls Solé J, Grimalt Santacana R, Rubio Garay M, Iglesias Sentís M (February 2004). "[Surgical treatment for compensatory hyperhidrosis in Adie syndrome]". Archivos De Bronconeumologia (in Spanish; Castilian). 40 (2): 97–9. PMID 14746734.