Hallervorden-Spatz Disease Clinical Presentation

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

History

Symptoms in Hallervorden-Spatz disease (HSD) include the following:

  • Dystonia - A prominent and early feature
  • Significant speech disturbances - Can occur early
  • Dysphagia - A common symptom; caused by rigidity and corticobulbar involvement
  • Dementia - Present in most individuals with HSD
  • Visual impairment - Caused by optic atrophy or retinal degeneration; not uncommon and can be the presenting symptom of the disease, although this is rare
  • Seizures - Have been described[17]

Clinical manifestations of HSD vary from patient to patient. The symptoms usually begin in the first decade with a motor disorder of extrapyramidal type and gait difficulty. Extrapyramidal symptoms dominate the clinical picture and include rigidity, slowness of movement, dystonia, choreoathetosis, and tremor.

In some patients, extrapyramidal dysfunction may be delayed for several years, and spasticity and dysarthria may be the presenting symptoms.

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Physical Examination

Physical examination reveals signs consistent with extrapyramidal and corticospinal dysfunction. In addition to rigidity, dystonia, and chorea, patients may exhibit spasticity, brisk reflexes, and extensor plantar responses.

Based on the common clinical features, the following diagnostic criteria for HSD have been proposed.[17] For a definitive diagnosis, all of the obligate findings and at least 2 of the corroborative findings should be present. None of the exclusionary factors should be present.

Obligate features of HSD include the following:

  • Onset during the first 2 decades of life
  • Progression of signs and symptoms
  • Evidence of extrapyramidal dysfunction, including 1 or more of the following: dystonia, rigidity, choreoathetosis

Corroborative features include the following:

  • Corticospinal tract involvement
  • Progressive intellectual impairment
  • Retinitis pigmentosa and/or optic atrophy
  • Seizures
  • Positive family history consistent with autosomal recessive inheritance
  • Hypointense areas on magnetic resonance imaging (MRI) involving the basal ganglia
  • Abnormal cytosomes in circulating lymphocytes and/or sea-blue histiocytes in bone marrow

Exclusionary features include the following:

  • Abnormal ceruloplasmin levels and/or abnormalities in copper metabolism
  • Presence of overt neuronal ceroid lipofuscinosis, as demonstrated by severe visual impairment and/or seizures that are difficult to control
  • Predominant epileptic symptoms
  • Severe retinal degeneration or visual impairment preceding other symptoms
  • Presence of familial history of Huntington chorea and/or other autosomal, dominantly inherited neuromovement disorders
  • Presence of caudate atrophy on imaging studies
  • Deficiency of hexosaminidase A
  • Deficiency of ganglioside monosialic acid-1 (GM1)–galactosidase
  • Nonprogressive course
  • Absence of extrapyramidal signs
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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].

 
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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.
 
 
 
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