Vilchez-Abreu C, Roa-Sanchez P, Fermin-Delgado R, Speckter H, Perez-Then E, Oviedo J, Stoeter P

Language: Spanish
References: 22
Page: 189-196
PDF size: 235.46 Kb.

ABSTRACT

Objective. Describe and quantify changes that occur with age in the “eye-of-the-tiger” sign in patients with pantothenate kinase-associated neurodegeneration.
Patients and methods. Magnetic resonances from 30 genetically confirmed patients (4 to 76 years) and 3 asymptomatic cases (7 to 11 years) were evaluated.
Results. The younger patients presented hyperintensity in the globus pallidus without the typical peripheral hypointensity. The majority, including the asymptomatic patients, presented “eye-of-the-tiger”. In 6 individuals this hyperintensity appeared darkened. The size of the hypointense area correlated significantly with age (p ‹ 0.01) but not with degree of dystonia p › 0.05).
Discussion. Changes in the “eye-of-the-tiger” sign represent an early lesion in the globus pallidus which turns into an area of gliosis. Iron accumulates with no relationship to dystonia and cannot be used as a parameter to measure progression of the disease.

REFERENCES

1. Hayflick SJ, Westaway SK, Levinson B, y col. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med 2003;348:33-40.

2. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 2001;28:345-349.

3. Hayflick SJ. Unraveling the Hallervorden-Spatz syndrome: pantothenate kinase-associated neurodegeneration is the name. Curr Opin Pediatr 2003;15:572-577.

4. Gregory A, Hayflick SJ. Neurodegeneration with brain iron accumulation. Folia Neuropathol 2005;43:286-296.

5. Pellecchia MT, Valente EM, Cif L, et al. The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration. Neurology 2005;64:1810-1812.

6. Bindu PS, Desai S, Shehanaz KE, Nethravathy M, Pal PK. Clinical heterogeneity in Hallervorden-Spatz syndrome: a clinicoradiological study in 13 patients from South India. Brain Dev 2006;28:343-347.

7. Trussart V, Leboucq N, Carlander B, Billiard M, Castan P. Hallervorden-Spatz syndrome and MRI: the "tiger's eye". One case. J Neuroradiol 1993;20:70-75.

8. Hayflick SJ, Hartman M, Coryell J, Gitschier J, Rowley H. Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations. Am J Neuroradiol 2006;27:1230-1233.

9. Kumar N, Boes CJ, Babovic-Vuksanovic D, Boeve BF. The "eye-of-the-tiger" sign is not pathognomonic of the PANK2 mutation. Arch Neurol 2006;63:292-293.

10. Baumeister FA, Auer DP, Hörtnagel K, Freisinger P, Meitinger T. The eye-of-the-tiger sign is not a reliable disease marker for Hallervorden-Spatz syndrome. Neuropediatrics 2005;36:221-222.

11. Zolkipli Z, Dahmoush H, Saunders DE, Chong WK, Surtees R. Pantothenate kinase 2 mutation with classic pantothenate- kinase-associated neurodegeneration without 'eye-ofthe- tiger' sign on MRI in a pair of siblings. Pediatr Radiol 2006;36:884-886.

12. Delgado RF, Sanchez PR, Speckter H, y col. 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 2012;35:788-794.

13. Hájek M, Adamovicová M, Herynek V, et al. MR relaxometry and 1H MR spectroscopy for the determination of iron and metabolite concentrations in PKAN patients. Eur Radiol 2005;15:1060-1068.

14. Gupta R, Kumar A, Sharma MC, Sarkar C, Goyal V, Bihari M. Autopsy always teach and tell: neurodegeneration with brain iron accumulation: a case report. Indian J Pathol Microbiol 2007;50:792-794.

15. Schipper HM. Neurodegeneration with brain iron accumulation - Clinical syndromes and neuroimaging. Biochim Biophys Acta 2012;1822:350-360.

16. Rossi D, De Grandis E, Barzaghi C, et al. Early-onset neurodegeneration with brain iron accumulation due to PANK2 mutation. Brain Dev 2012;34:536-538.

17. Aquino D, Bizzi A, Grisoli M, et al. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology 2009;252:165-172.

18. Vymazal J, Brooks RA, Patronas N, Hajek M, Bulte JW, Di Chiro G. Magnetic resonance imaging of brain iron in health and disease. J Neurol Sci 1995;134(Supp l):19-26.

19. Vymazal J, Brooks RA, Baumgarner C, et al. The relation between brain iron and NMR relaxation times: an in vitro study. Magn Reson Med 1996;35:56-61.

20. Carbon M, Eidelberg D. Abnormal structure-function relationships in hereditary dystonia. Neuroscience 2009;164:220-229.

21. Zorzi G, Zibordi F, Chiapparini L, et al. Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: results of a phase II pilot trial. Mov Disord 2011;26:1756-1759.

22. Stoeter P, Rodriguez-Raecke R, Vilchez C, et al. Motor activation in patients with Pantothenate Kinase-Associated Neurodegeneration: a functional Magnetic Resonance Imaging study. Parkinsonism Relat Disord 2012;18:1007-1010.