Pantothenate kinase-associated neurodegeneration
Pantothenate kinase-associated neurodegeneration (PKAN), previously known as Hallervorden-Spatz syndrome, is an autosomal recessive disorder causing involuntary spasticity and progressive dementia. It is a subset of neurodegeneration with brain iron accumulation (NBIA).
Classical PKAN tends to have onset before 6 years of age, whereas atypical PKAN manifests at a mean age of 14 years 10. Prevalence is estimated around 1-3 per million 10.
Described features include 9,11:
- progressive dementia
- extrapyramidal signs (rigidity, dystonia, choreoathetosis)
- corticospinal signs (spasticity, hyper-reflexia)
- retinitis pigmentosa
The clinical course is usually relentlessly progressive with affected individuals dying in their second or third decade.
Reflects areas of iron deposition, mainly globi pallidi, substantia nigra, and red nuclei.
- T2: T2-weighted MRI images often demonstrate hypointense changes in globi pallidi and pars reticulata of substantia nigra
- SWI/T2*: shows susceptibility artefact (low signal) in corresponding areas from iron deposition 7
Cortex is usually spared but caudate atrophy may be seen in more advanced cases. The "eye of the tiger" sign refers to a central T2 relatively hyperintense spot (line) within the hypointense globi pallidi due to gliosis and vacualisation 3.
- shows decreased NAA peak due to neuronal loss and may show increased myoinositol 8
History and etymology
It was previously named after 4:
- Julius Hallervorden (1882-1965): Neuropathologist, Germany
- Hugo Spatz (1888-1969): Anatomist, Munich, Germany
Both Hugo Spatz and Julius Hallervorden were involved in the Nazi euthanasia program and, as such, the alternative name is preferred by some authors. Brief biographical entries on Spatz and Hallervorden make an interesting reading 1.
- 1. Hallervorden-Spatz syndrome from whonamedit.com, the dictionary of medical eponyms. Hallervorden-Spatz syndrome
- 2. Savoiardo M, Halliday WC, Nardocci N et-al. Hallervorden-Spatz disease: MR and pathologic findings. AJNR Am J Neuroradiol. 14 (1): 155-62. AJNR Am J Neuroradiol (abstract) - Pubmed citation
- 3. Guillerman RP. The eye-of-the-tiger sign. Radiology. 2000;217 (3): 895-6. Radiology (full text) - Pubmed citation
- 4. Hallervorden, H. Spatz: Eigenartige Erkrankung im extrapyramidalen System mit besonderer Beteiligung des Globus pallidus und der Substantia nigra: Ein Beitrag zu den Beziehungen zwischen diesen beiden Zentren. Zeitschrift für die gesamte Neurologie und Psychiatrie, 1922, 79: 254-302.
- 5. Chavhan GB, Shroff MM. Twenty classic signs in neuroradiology: A pictorial essay. Indian J Radiol Imaging. 2009, 19 (2): 135-45. doi:10.4103/0971-3026.50835 - Free text at pubmed - Pubmed citation
- 6. Yang S-K, Hu C-J, Yuan R-Y, Wang H-J, Sheu J-J. Presence of the Eye-of-the-tiger Sign on Magnetic Resonance Imaging in a Subject with Atypical Hallervorden-Spatz Syndrome Lacking Pantothenate Kinase 2 Mutation. J. Exp. Clin. Med. [Internet]. Elsevier; 2012 Feb 1 [cited 2013 Nov 12];4(1):73–4. Journal of Experimental and Clinical Medicine citation
- 7. Bosemani T, Meoded A, Poretti A. Susceptibility-Weighted Imaging in Pantothenate Kinase-Associated Neurodegeneration. J. Pediatr. [Internet]. 2013 Oct 7 [cited 2013 Nov 12]. Pubmed citation
- 8. Sener RN. Pantothenate kinase-associated neurodegeneration: MR imaging, proton MR spectroscopy, and diffusion MR imaging findings. AJNR Am J Neuroradiol. 2003;24 (8): 1690-3. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 9. Asumal KB, Wasay M, Ali SN. Radiologic features of Hallervorden Spatz Disease. J Pak Med Assoc. 2003;52 (11): 528-30. Pubmed citation
- 10. Kurian MA, Hayflick SJ. Pantothenate kinase-associated neurodegeneration (PKAN) and PLA2G6-associated neurodegeneration (PLAN): review of two major neurodegeneration with brain iron accumulation (NBIA) phenotypes. (2013) International review of neurobiology. 110: 49-71. doi:10.1016/B978-0-12-410502-7.00003-X - Pubmed
- 11. Dashti M, Chitsaz A. Hallervorden-Spatz disease. (2014) Advanced biomedical research. 3: 191. doi:10.4103/2277-9175.140623 - Pubmed