Ross Syndrome

From EyeWiki


Clinicians should be aware of the Ross Syndrome (RS) including the triad of pupillary light near dissociation (tonic pupils), variable anhidrosis, and areflexia. Other autonomic nervous system involvement including GI and cardiac should be evaluated in RS. The autonomic thermodysregulation may be potentially dangerous and although RS has no cure, countermeasures to prevent overheating are recommended for symptomatic patients.

Disease Entity

ICD-10: L74.8 (ILDS L74.840)

Disease

Ross syndrome (RS) is a rare disorder of the peripheral autonomic nervous system that is characterized by the triad: tonic pupils, reduced or loss of deep tendon reflexes (hyporeflexia or areflexia), and anhidrosis or hypohidrosis. The first case was reported by Dr. Ross in 1958 and there have only been around 50 cases described in the literature thus far.[1] Whether this condition is distinct from Holmes–Adie syndrome (tonic pupil and hyporeflexia) and from Harlequin syndrome (segmental hypohidrosis without pupillary abnormalities) has not yet been elucidated due to the rarity of the condition.

Epidemiology

Nolano reported 12 patients with RS and suggested that many cases may be undiagnosed.[2] The diagnosis of RS in these series was often made only after many years of unexplained autonomic symptoms and signs.

RS is a progressive autonomic dysfunction that can occur in any age, ethnicity, or gender. The average age of diagnosis is 36 years and RS has a slight female predominance.[2]

Pathogenesis and Causes

The exact pathogenesis of RS is not known. However, researchers believe there is a nonspecific degeneration of parasympathetic neuronal structures.[3] Anhidrosis or hypohidrosis likely stems from degeneration of sympathetic ganglion cells or postganglionic projections. There also appears to be a loss of regulation of skin blood flow resulting in upper large and dilated dermal blood vessels. The tonic pupil stems from damage to the ciliary ganglion or postganglionic parasympathetic nerve fibers. The loss of deep tendon reflexes may stem from damage to the dorsal root ganglia or spinal interneuron loss.

A possible autoimmune pathogenic mechanism for RS has also been proposed.[4] Serum antinuclear antibody (ANA) positivity has been reported in a subset of RS. Another study proposed that RS may be an α-synucleinopathy after detecting the accumulation of α-Syn in autonomic nerve endings in the lesser curvature of the stomach.[5]

Diagnosis

The diagnosis of RS is usually clinical but the complete RS triad may not be present initially. The tonic pupil produces variable anisocoria that is worse in the light than in the dark. The pupillary reaction to light is typically impaired but preserved to accommodative stimulus (i.e. light-near dissociation). In the RS, the pupil abnormality is typically bilateral. Light near dissociation of the pupils is not specific for the RS and can also be found in patients with bilateral anterior afferent visual pathway disease, Argyll Robertson pupil, diabetes, or dorsal midbrain lesions.[6] The denervated sphincter muscles can show increased sensitivity to diluted pilocarpine (0.125%) due to up regulation of receptors in up to 80% of cases.

Signs and Symptoms

RS presents with unilateral or bilateral anhidrosis, tonic pupils, and hyporeflexia. Additionally, various symptoms of autonomic dysfunction in RS may include gastrointestinal paresis, impotence and sexual dysfunction, orthostatic hypotension, Parkinsonism, and urinary incontinence.

Differential diagnosis

  1. Harlequin syndrome presents with segmental hypohidrosis in addition to normal pupils and reflexes[7]
  2. Holmes-Adie syndrome presents with tonic pupil, areflexia, and absence of sweating changes[8]
  3. Horner syndrome presents with small pupils, ptosis, normal reflexes, and anhidrosis

General treatment and Prognosis

Currently, therapeutic options for RS are restricted to symptomatic management.[2] Therapeutic options for RS are similar to other primary or secondary hyperhidrosis. General cooling measures including wearing loose clothing and avoiding hot environments or heavy exertion are recommended. Antiperspirants containing aluminium chloride 10–25% are also used to prevent excess sweating but may worsen over heating.

There have been research that also shows anticholinergic medications including oxybutynin and glycopyrrolate to inhibit the effect of acetylcholine on the sweat glands.[9] While they can be useful to reduce sweating, there are side effects, including dry mouth, blurred vision, constipation, and urinary retention. Botulinum toxin injections, iontophoresis, and sympathectomy, have also been used in the treatment of severe hyperhidrosis. For patients with ANA positivity, Vasudevan et al presented a case of a patient with ANA positivity who was successfully treated with intravenous immunoglobulin.4

Summary

Clinicians should be aware of the Ross Syndrome (RS) including the triad of pupillary light near dissociation (tonic pupils), variable anhidrosis, and areflexia. Other autonomic nervous system involvement including GI and cardiac should be evaluated in RS. The autonomic thermodysregulation may be potentially dangerous and although RS has no cure, countermeasures to prevent overheating are recommended for symptomatic patients.

References

  1. Filikci Z, Horsten H-H, Lindelof M. Ross Syndrome: A Patient with a 23-Year History. Case Reports in Neurology. 2020;12(1). doi:10.1159/000507186
  2. 2.0 2.1 2.2 Nolano M. Ross syndrome: a rare or a misknown disorder of thermoregulation? A skin innervation study on 12 subjects. Brain. 2006;129(8). doi:10.1093/brain/awl175
  3. Mullaaziz D, Kaptanoglu AF, Eker A. Hypohidrosis or hyperhidrosis? Ross syndrome. Dermatologica Sinica. 2016;34(3). doi:10.1016/j.dsi.2015.10.004
  4. Vasudevan B, Sawhney M, Vishal S. Ross syndrome with ANA positivity: A clue to possible autoimmune origin and treatment with intravenous immunoglobulin. Indian Journal of Dermatology. 2010;55(3). doi:10.4103/0019-5154.70694
  5. Ma M, Yao J, Chen Y, et al. Is Ross Syndrome a New Type of Synucleinopathy? A Brief Research Report. Frontiers in Neuroscience. 2020;14. doi:10.3389/fnins.2020.00635
  6. 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;133(3). doi:10.1016/S0002-9394(01)01420-9
  7. Algahtani H, Shirah B, Algahtani R, Alkahtani A. Idiopathic Harlequin Syndrome Manifesting during Exercise: A Case Report and Review of the Literature. Case Reports in Medicine. 2017;2017. doi:10.1155/2017/5342593
  8. COLAK S, ERDOGAN MO, SENEL A, et al. A Rare Case in the Emergency Department: Holmes-Adie Syndrome. Turkish Journal of Emergency Medicine. 2015;15(1). doi:10.5505/1304.7361.2015.59144
  9. Panda S, Verma D, Budania A, Bharti J, Sharma R. Clinical and laboratory correlates of selective autonomic dysfunction due to Ross syndrome. Journal of Family Medicine and Primary Care. 2019;8(4). doi:10.4103/jfmpc.jfmpc_151_19
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