Hallervorden-Spatz Disease Medication

  • Author: Philip A Hanna, MD; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Feb 28, 2012
 

Medication Summary

As previously mentioned, dopaminergic agents, such as levodopa and bromocriptine, can produce modest improvements in dystonia. If dopaminergic agents are not effective against dystonia, anticholinergics can be used, but they offer only transient relief. Botulinum toxin injections also can improve dystonic muscles.

Agents used to relieve rigidity and spasticity may prove effective against dysarthria, while methscopolamine bromide can deter excessive drooling.

Next

Antiparkinson Agents, Dopamine Agonists

Class Summary

These agents reduce morbidity associated with dopamine deficiency.

View full drug information

Levodopa/carbidopa (Sinemet, Sinemet CR, Parcopa)

 

Carbidopa (a decarboxylase inhibitor) is administered with levodopa to prevent the breakdown of levodopa and increase levodopa's bioavailability. Thus, carbidopa decreases the need for large doses of levodopa to achieve adequate brain dopamine levels. The levodopa/carbidopa combination is often used when symptom control with selegiline alone is insufficient. The CR levodopa/carbidopa formulation can help to prevent the on/off phenomenon in some patients.

The Sinemet tablet is available in a 4:1 ratio (Sinemet 100/25) and a 10:1 ratio (Sinemet 100/10 and 250/25) of levodopa to carbidopa. The Sinemet CR tablet contains a 4:1 ratio of levodopa to carbidopa (100/25 or 200/50); the daily dosage of Sinemet CR must be determined by careful titration.

View full drug information

Bromocriptine (Parlodel, Cycloset)

 

Bromocriptine is a semisynthetic ergot alkaloid derivative. It is a strong dopamine D2-receptor agonist and a partial dopamine D1-receptor agonist. Bromocriptine may relieve akinesia, rigidity, and tremor associated with Parkinson disease. It stimulates dopamine receptors in the corpus striatum. It is, however, less effective than other dopamine agonists. It can be used as an adjunct to levodopa/carbidopa.

Approximately 28% of the drug is absorbed from the gastrointestinal (GI) tract and metabolized in the liver. The approximate elimination half-life is 50 hours, with 85% of bromocriptine excreted in feces and 3-6% eliminated in urine. The drug is initiated at a low dose with slow titration; increase in the dose every 2 weeks. If severe adverse reactions occur, the dose is reduced in 2.5-mg decrements.

Previous
Next

Antiparkinson Agents, Anticholinergics

Class Summary

These agents are thought to act centrally by suppressing the conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.

View full drug information

Trihexyphenidyl

 

This is a centrally acting anticholinergic agent that tends to diminish the muscle spasms.

View full drug information

Benztropine (Cogentin)

 

By blocking the striatal cholinergic receptors, benztropine may help in balancing the cholinergic and the dopaminergic activity in the striatum.

View full drug information

Scopolamine (Transderm Scop Patch, Scopace)

 

Scopolamine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system (CNS). It antagonizes the action of histamine and serotonin.

Previous
Next

Benzodiazepines

Class Summary

By binding to the specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

View full drug information

Clonazepam (Klonopin)

 

Clonazepam suppresses the muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters.

Previous
Next

Neuromuscular Blocker Agents, Botulinum Toxins

Class Summary

These agents produce symptomatic improvement in muscle strength by relieving spasticity and autonomic symptoms, or both in some patients.

View full drug information

Botulinum toxin type A (BOTOX)

 

This agent binds to the receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which, in turn, inhibits the transmission of impulses at the neuromuscular junction.

Previous
 
Contributor Information and Disclosures
Author

Philip A Hanna, MD  Associate Professor, Department of Neuroscience, Seton Hall University School of Graduate Medical Education; Residency Program Director, New Jersey Neuroscience Institute, JFK Medical Center; Neurology Director, Huntington's Disease Unit, JFK Hartwyck-Cedarbrook

Philip A Hanna, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Movement Disorders Society

Disclosure: Nothing to disclose.

Coauthor(s)

Neeta Garg, MD, DM  Assistant Professor, Department of Neurology, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Neeta Garg, MD, DM is a member of the following medical societies: American Academy of Neurology

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.

Brian L Gerhardstein, MD, PhD Staff Physician, Department of Neurology, New Jersey Neuroscience Institute, JFK Medical Center

Disclosure: Nothing to disclose.

Christopher Luzzio, MD Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison

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; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

References

  1. Neumann M, Adler S, Schluter O, et al. Alpha-synuclein accumulation in a case of neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome) with widespread cortical and brainstem-type Lewy bodies. Acta Neuropathol (Berl). Nov 2000;100(5):568-74. [Medline].

  2. Szumowski J, Bas E, Gaarder K, Schwarz E, Erdogmus D, Hayflick S. Measurement of brain iron distribution in Hallevorden-Spatz syndrome. J Magn Reson Imaging. Feb 2010;31(2):482-9. [Medline].

  3. Schneider SA, Hardy J, Bhatia K. Iron Accumulation in Syndromes of Neurodegeneration with Brain Iron Accumulation 1 and 2 - causative or consequential?. J Neurol Neurosurg Psychiatry. Jan 15 2009;[Medline].

  4. Jankovic J, Kirkpatrick JB, Blomquist KA, et al. Late-onset Hallervorden-Spatz disease presenting as familial parkinsonism. Neurology. Feb 1985;35(2):227-34. [Medline].

  5. Grimes DA, Lang AE, Bergeron C. Late adult onset chorea with typical pathology of Hallervorden-Spatz syndrome. J Neurol Neurosurg Psychiatry. Sep 2000;69(3):392-5. [Medline].

  6. Cooper GE, Rizzo M, Jones RD. Adult-onset Hallervorden-Spatz syndrome presenting as cortical dementia. Alzheimer Dis Assoc Disord. Apr-Jun 2000;14(2):120-6. [Medline].

  7. Saito Y, Kawai M, Inoue K, et al. Widespread expression of alpha-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protracted clinical course. J Neurol Sci. Aug 1 2000;177(1):48-59. [Medline].

  8. Hickman SJ, Ward NS, Surtees RA, et al. How broad is the phenotype of Hallervorden-Spatz disease?. Acta Neurol Scand. Mar 2001;103(3):201-3. [Medline].

  9. Taylor TD, Litt M, Kramer P, et al. Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13. Nat Genet. Dec 1996;14(4):479-81. [Medline].

  10. Zhou B, Westaway SK, Levinson B, et al. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden- Spatz syndrome. Nat Genet. Aug 2001;28(4):345-9. [Medline].

  11. Perry TL, Norman MG, Yong VW, et al. Hallervorden-Spatz disease: cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus. Ann Neurol. Oct 1985;18(4):482-9. [Medline].

  12. Hayflick SJ. First scientific workshop on Hallervorden-Spatz syndrome: executive summary. Pediatr Neurol. Aug 2001;25(2):99-101. [Medline].

  13. Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet. Feb 2009;46(2):73-80. [Medline].

  14. Johnson MA, Kuo YM, Westaway SK, et al. Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Ann N Y Acad Sci. Mar 2004;1012:282-98. [Medline].

  15. Kotzbauer PT, Truax AC, Trojanowski JQ, Lee VM. Altered neuronal mitochondrial coenzyme a synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. J Neurosci. Jan 19 2005;25(3):689-98. [Medline].

  16. Leoni V, Strittmatter L, Zorzi G, et al. Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations. Mol Genet Metab. Dec 14 2011;[Medline].

  17. Swaiman KF. Hallervorden-Spatz syndrome and brain iron metabolism. Arch Neurol. Dec 1991;48(12):1285-93. [Medline].

  18. Halliday W. The nosology of Hallervorden-spatz disease. J Neurol Sci. Dec 1995;134 Suppl:84-91. [Medline].

  19. Vakili S, Drew AL, Von Schuching S, et al. Hallervorden-Spatz syndrome. Arch Neurol. Dec 1977;34(12):729-38. [Medline].

  20. Zimmerman AW, Stover ML, Grasso JA, et al. Uptake of 59Fe by skin fibroblasts and MAO activity in platelets from patients with Hallervorden-Spatz syndrome. Neurology. 1981;51:48.

  21. Swaiman KF, Smith SA, Trock GL, et al. Sea-blue histiocytes, lymphocytic cytosomes, movement disorder and 59Fe- uptake in basal ganglia: Hallervorden-Spatz disease or ceroid storage disease with abnormal isotope scan?. Neurology. Mar 1983;33(3):301-5. [Medline].

  22. Alberca R, Rafel E, Chinchon I, et al. Late onset parkinsonian syndrome in Hallervorden-Spatz disease. J Neurol Neurosurg Psychiatry. Dec 1987;50(12):1665-8. [Medline].

  23. Hermann W, Reuter M, Barthel H, et al. Diagnosis of Hallervorden-Spatz disease using MRI, (123)I-beta-CIT- SPECT and (123)I-IBZM-SPECT. Eur Neurol. 2000;43(3):187-8. [Medline].

  24. Feliciani M, Curatolo P. Early clinical and imaging (high-field MRI) diagnosis of Hallervorden- Spatz disease. Neuroradiology. Apr 1994;36(3):247-8. [Medline].

  25. Shah J, Patkar D, Patankar T, et al. Hallervorden Spatz disease: MR imaging. J Postgrad Med. Oct-Dec 1999;45(4):114-7. [Medline].

  26. McNeill A, Birchall D, Hayflick SJ, Gregory A, Schenk JF, Zimmerman EA, et al. T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology. Apr 29 2008;70(18):1614-9. [Medline].

  27. Sethi KD, Adams RJ, Loring DW, et al. Hallervorden-Spatz syndrome: clinical and magnetic resonance imaging correlations. Ann Neurol. Nov 1988;24(5):692-4. [Medline].

  28. Delgado RF, Sanchez PR, Speckter H, et al. Missense PANK2 mutation without "Eye of the tiger" sign: MR findings in a large group of patients with pantothenate kinase-associated neurodegeneration (PKAN). J Magn Reson Imaging. Nov 29 2011;[Medline].

  29. Chiapparini L, Savoiardo M, D'Arrigo S, et al. The "eye-of-the-tiger" sign may be absent in the early stages of classic pantothenate kinase associated neurodegeneration. Neuropediatrics. Aug 2011;42(4):159-62. [Medline].

  30. Justesen CR, Penn RD, Kroin JS, et al. Stereotactic pallidotomy in a child with Hallervorden-Spatz disease. Case report. J Neurosurg. Mar 1999;90(3):551-4. [Medline].

  31. Mikati MA, Yehya A, Darwish H, Karam P, Comair Y. Deep brain stimulation as a mode of treatment of early onset pantothenate kinase-associated neurodegeneration. Eur J Paediatr Neurol. Jan 2009;13(1):61-4. [Medline].

  32. Castelnau P, Cif L, Valente EM, Vayssiere N, Hemm S, Gannau A, et al. Pallidal stimulation improves pantothenate kinase-associated neurodegeneration. Ann Neurol. May 2005;57(5):738-41. [Medline].

 
Previous
Next
 
Magnetic resonance imaging (MRI) has increased the likelihood of antemortem diagnosis of Hallervorden-Spatz (HSD) disease. The typical MRI findings include bilaterally symmetrical, hyperintense signal changes in the anterior medial globus pallidus, with surrounding hypointensity in the globus pallidus, on T2-weighted images. These imaging features, which are fairly diagnostic of HSD, have been termed the "eye-of-the-tiger sign." The hyperintensity represents pathologic changes, including gliosis, demyelination, neuronal loss, and axonal swelling. The surrounding hypointensity is due to loss of signal secondary to iron deposition.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.