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Horner Syndrome: Differential Diagnoses & Workup

Author: Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine; Consulting Physician, Timmins and District Hospital, Ontario, Canada
Contributor Information and Disclosures

Updated: Nov 24, 2009

Differential Diagnoses

Anisocoria

Other Problems to Be Considered

Senile miosis
Argyll Robertson pupil
Miotic drugs
Holmes-Adie pupil (contralateral)

Workup

Imaging Studies

  • Obtain a chest radiograph because apical bronchogenic carcinoma is the most common cause of Horner syndrome.
  • Perform a head CT scan if stroke is suspected.
  • In painful Horner syndrome, obtain a magnetic resonance angiography of the brain with cross-sectional imaging of the neck to evaluate the possibility of carotid artery dissection.
  • Ultrasound has been found to be unreliable for diagnosing carotid artery dissection in patients with isolated Horner syndrome.15

Procedures

The following pharmacologic tests document the presence or absence of an ocular sympathetic lesion and identify the level of involvement (ie, preganglionic or postganglionic). Localizing the lesion is important because preganglionic lesions are associated with a higher incidence of malignancy that requires extensive investigations.

Test to document ocular sympathetic lesion

  • Topical cocaine test 
    • Agent - Cocaine (2-4%)
    • Normal response - Dilatation
    • Horner syndrome - No response
    • Mechanism - Cocaine acts as an indirect sympathomimetic agent by inhibiting the reuptake of norepinephrine at the nerve ending. Hence, mydriasis occurs in the normal pupil but not in the norepinephrine-deficient Horner pupil.
    • Remarks - To ensure accuracy, evaluate test results approximately 30 minutes after administering cocaine.
    • Disadvantage - Controlled substance, lack of availability, its metabolites may be detected in urine
  • Topical apraclonidine test - The current test of choice 
    • Agent - Apraclonidine (0.5%)16,17,18
    • Normal response - Relative miosis
    • Horner syndrome - Relative mydriasis and reversal of ptosis
    • Mechanism - Apraclonidine is a weak alpha1-agonist and a strong alpha2-agonist. In Horner syndrome, there is upregulation of alpha1-receptors that increases apraclonidine sensitivity. The denervation supersensitivity results in pupillary dilatation and lid elevation on the abnormal side but no response or mild miosis on the normal side from alpha2-activity following apraclonidine.
    • Remarks - Apraclonidine is readily available and has adequate sensitivity of 87%.17 Its mydriatic effect on abnormal pupil makes for easier interpretation.
    • In acute cases, false-negative test results may occur because the effect of apraclonidine is dependent on upregulation of alpha1-receptors that may take 5-8 days.19 Hence, a negative test result, especially in acute settings, does not exclude Horner syndrome, and a cocaine test should be considered.

Test to localize lesion (preganglionic or postganglionic)

  • Hydroxyamphetamine test
    • Agent - Hydroxyamphetamine (1%)
    • Normal response - Dilation (preganglionic lesion)
    • Horner syndrome - No response, indicates postganglionic lesion
    • Mechanism - Hydroxyamphetamine promotes the release of stored endogenous norepinephrine from the postganglionic axon terminals into the neuromuscular junction at the iris dilator muscles, meaning that if the postganglionic cell and its terminals at the dilator muscles are intact, hydroxyamphetamine will release the stored norepinephrine and block norepinephrine uptake, and both actions will bring pupillary dilatation.
    • Remarks - At least 24 hours must elapse between the cocaine and the hydroxyamphetamine tests because cocaine has the ability to inhibit the uptake of hydroxyamphetamine into the presynaptic vesicles, which will reduce accuracy.

More on Horner Syndrome

Overview: Horner Syndrome
Differential Diagnoses & Workup: Horner Syndrome
Treatment & Medication: Horner Syndrome
Follow-up: Horner Syndrome
References
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References

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Further Reading

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Keywords

Bernard syndrome, Bernard-Horner syndrome, Horner syndrome, Horner's syndrome, Horner’s oculopupillary syndrome, Horner oculopupillary syndrome, Horner’s sign, Horner sign, Horner's symptom complex, Horner symptom complex, Horner's triad, Horner triad, Hutchinson’s syndrome, Hutchinson syndrome, Mitchell’s syndrome III, Mitchell syndrome, oculosympathetic paralysis, Raeder paratrigeminal syndrome, Raeder’s paratrigeminal syndrome, heterochromia irides, von Passow’s syndrome, von Passow syndrome, miosis, constricted pupil, partial ptosis, hemifacial sweat, hemifacial anhidrosis, facial sweating, facial flushing, harlequin effect  

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Contributor Information and Disclosures

Author

Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine; Consulting Physician, Timmins and District Hospital, Ontario, Canada
Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Philip Schulman, MD, Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine
Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, and Medical Society of the State of New York
Disclosure: celgene Honoraria Speaking and teaching; Amgen Honoraria Speaking and teaching; genetech/idec Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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