Neurologic Manifestations of Wilson Disease 

  • Author: Celia H Chang, MD; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Nov 8, 2011
 

Clinical and Histologic Findings

Neurologic signs

Neurologic signs of Wilson disease[1, 2] include the following:

  • Parkinsonian symptoms - Rigidity, bradykinesia
  • Dysarthria
  • Tremor at rest or with action
  • Dystonia, mainly of the face
  • Dysdiadochokinesia
  • Poor handwriting
  • Incoordination
  • Abnormal eye movements
  • Respiratory dyskinesia, which can present as an unusual cough[3]
  • Polyneuropathy, which may be the initial manifestation and may be reversible with treatment[4]

Psychiatric signs

Psychiatric signs include the following:

  • Hyperkinetic behavior
  • Irritability or anger
  • Emotional lability
  • Psychosis
  • Mania
  • Difficulty concentrating
  • Abnormal behavior
  • Personality changes
  • Depression
  • Schizophrenia

Ophthalmic findings

A characteristic ophthalmic finding is Kayser-Fleischer (KF) rings.[5, 6, 7] KF rings are greenish-yellow or brown rings seen at the limbus of the cornea. They are usually best visualized on slit-lamp examination. Typically, KF rings originate at the superior pole, then progress to both the superior and inferior poles, and finally form a full circle. They may not be present in children or other individuals without neurologic symptoms.

Sunflower cataracts are brilliantly multicolored and are visible only on slit-lamp examination. They do not impair vision. Other relatively uncommon ophthalmic findings include exotropic strabismus, optic neuritis or pallor of the optic disc, and night blindness.

Histologic findings

Histologic findings in the brain include the following:

  • Copper deposition in the basal ganglia
  • Opalski cells - Periodic acid-Schiff–positive altered glial cells
  • Cavitary degeneration
  • Gliosis
  • Neuronal loss
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Differential Diagnosis

The differential diagnosis includes the following conditions:

Drug-induced parkinsonism should be considered. The following agents may play a role:

  • Neuroleptics
  • Antiemetics - Metoclopramide
  • Antihypertensives - Verapamil, methyldopa, reserpine
  • Flunarizine
  • Lovastatin
  • Amiodarone
  • Cytosine arabinoside

Parkinsonism induced by any of the following toxins should also be considered:

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
  • Carbon monoxide
  • Cyanide
  • Manganese
  • Industrial chemicals - Diquat, carbon disulfide, methanol, N -hexane, lacquer thinners

Miscellaneous conditions that may give rise to symptoms and signs similar to the neurologic manifestations of Wilson disease include the following:

  • Vascular parkinsonism
  • Structural lesions
  • Hydrocephalus
  • Metabolic parkinsonism - Hypothyroidism, hyperthyroidism, hypoparathyroidism
  • Posttraumatic parkinsonism - Dementia pugilistica
  • Hemiatrophy hemiparkinsonism
  • Postencephalitic parkinsonism

The differential diagnosis for pigmented corneal rings includes the following:

  • Carotenemia arcus senilis
  • Chronic active hepatitis
  • Chronic cholestasis
  • Chronic jaundice
  • Cryptogenic cirrhosis
  • Intraocular foreign body with less than 85% copper (if copper exceeds 85%, a severe suppurative inflammatory reaction is usually present)
  • Multiple myeloma
  • Primary biliary cirrhosis
  • Topical copper solution treatment of the eye
  • Trypanosomiasis
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Contributor Information and Disclosures
Author

Celia H Chang, MD  Associate Health Sciences Clinical Professor, Department of Neurology, University of California, Davis, School of Medicine

Celia H Chang, MD is a member of the following medical societies: American Academy of Neurology and Child Neurology Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Additional Contributors

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

References

  1. Czlonkowska A, Tarnacka B, Möller JC, Leinweber B, Bandmann O, Woimant F, et al. Unified Wilson's Disease Rating Scale - a proposal for the neurological scoring of Wilson's disease patients. Neurol Neurochir Pol. Jan-Feb 2007;41(1):1-12. [Medline].

  2. Brewer GJ. Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatment. CNS Drugs. 2005;19(3):185-92. [Medline].

  3. Crone NE, Jinnah HA, Reich SG. Wilson's disease presenting with an unusual cough. Mov Disord. Jul 2005;20(7):891-3. [Medline].

  4. Jung KH, Ahn TB, Jeon BS. Wilson disease with an initial manifestation of polyneuropathy. Arch Neurol. Oct 2005;62(10):1628-31. [Medline].

  5. Kashani AA. Wilson's disease: presymptomatic patients and Kayser-Fleischer rings. Ophthalmic Genet. Dec 1998;19(4):215-8. [Medline].

  6. Oracz G, Klimczak-Slaczka D, Sokolowska-Oracz A, Socha P, Gralek M, Szaflik J, et al. [Prevalence of Kayser-Fleischer ring in patients with Wilson's disease]. Klin Oczna. 2005;107(1-3):54-6. [Medline].

  7. Wiebers DO, Hollenhorst RW, Goldstein NP. The ophthalmologic manifestations of Wilson's disease. Mayo Clin Proc. Jul 1977;52(7):409-16. [Medline].

 
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