Top

Published in:

01-05-2012 | Original Communication

Transcranial sonography in pantothenate kinase-associated neurodegeneration

Authors: Vladimir S. Kostić, Marina Svetel, Milija Mijajlović, Aleksandra Pavlović, Milica Ječmenica-Lukić, Dušan Kozić

Published in: Journal of Neurology | Issue 5/2012

Abstract

After it was reported that increased tissue iron concentrations were associated with increased echogenicity of the substantia nigra (SN) obtained with transcranial sonography (TCS) in animal and postmortem studies, our goal was to use this method in a disorder characterized with iron accumulation in human brain tissue. Therefore, magnetic resonance imaging (MRI) and TCS were conducted in 5 unrelated patients with pantothenate kinase-associated neurodegeneration (PKAN), caused by PANK2 mutations. All patients had an eye of the tiger sign. Hypointense lesions on the T2-weighted MRI images were restricted to the globus pallidus (GP) and SN. TCS also revealed bilateral hyperechogenicity restricted to the LN and SN, with normal DTV values. Both TCS and MRI studies in PKAN patients are in accordance with the pathological findings that accumulation of iron, even in advanced cases, is restricted to the GP and SN, suggesting selective involvement of these structures.

Becker G, Seufert J, Bogdahn U, Reichmann H, Reiners K (1995) Degeneration of substantia nigra in chronic Parkinsonʼs disease visualized by transcranial color-coded real-time sonography. Neurology 45:182–184PubMedCrossRef

Berg D, Siefker C, Becker G (2001) Echogenicity of the substantia nigra in Parkinsonʼs disease and its relation to clinical findings. J Neurol 248:684–689PubMedCrossRef

Walter U, Wittstock M, Benecke R, Dressler D (2002) Substantia nigra echogenicity is normal in non-extrapyramidal cerebral disorders but increased in Parkinsonʼs disease. J Neural Transm 109:191–196PubMedCrossRef

Berg D, Godau J, Walter U (2008) Transcranial sonography in movement disorders. Lancet Neurol 7:1044–1053PubMedCrossRef

Skoloudík D, Walter U (2010) Method and validity of transcranial sonography in movement disorders. Int Rev Neurobiol 90:7–34PubMedCrossRef

Berg D, Becker G, Zeiler B et al (1999) Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology 53:1026–1031PubMedCrossRef

Berg D, Roggendorf W, Schroder U et al (2002) Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 59:999–1005PubMedCrossRef

Hochstrasser H, Bauer P, Walter U et al (2004) Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease. Neurology 63:1912–1917PubMedCrossRef

Berg D, Hochstrasser H, Schweitzer KJ, Riess O (2006) Disturbance of iron metabolism in Parkinsonʼs disease—ultrasonography as a biomarker. Neurotoxic Res 9:1–13CrossRef

10.

Berg D, Godau J, Riederer P, Gerlach M, Arzbetrger T (2010) Microglia activation is related to substantia nigra echogenicity. J Neural Transm 117:1287–1292PubMedCrossRef

11.

Hayflick SJ, Westaway SK, Levinson B et al (2003) Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med 348:33–40PubMedCrossRef

12.

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

13.

Hartig MB, Hortnagel K, Garavaglia B et al (2006) Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann Neurol 59:248–256PubMedCrossRef

14.

Mijajlović M, Petrović I, Stojković T, Svetel M, Stefanova E, Kostić VS (2008) Transcranial parenchymal sonography in Parkinson’s disease. Vojnosanit Pregl 65:601–605PubMedCrossRef

15.

Huber H (2010) Transcranial sonography–anatomy. Int Rev Neurobiol 90:35–45PubMedCrossRef

16.

Gregory A, Hayflick SJ (2005) Neurodegeneration with brain iron accumulation. Folia Neuropathol 43:286–296PubMed

17.

Berg D, Grote C, Rausch WD et al (1999) Iron accumulation in the substantia nigra in rats visualized by ultrasound. Ultrasound Med Biol 25:901–904PubMedCrossRef

18.

Zecca L, Berg D, Arzberger T et al (2005) In vivo detection of iron and neuromelanin by transcranial sonography: a new approach for early detection of substantia nigra damage. Mov Disord 20:1278–1285PubMedCrossRef

19.

Spatz H (1922) Uber des Eisenmachweiss im Gehirn besonders in Zentren des extra-pyramidalmotorischen Systems. Z Gesamte Neurol Psychiatr 77:261CrossRef

20.

Swaiman KF (1991) Hallervorden-Spatz syndrome and iron brain metabolism. Arch Neurol 48:1285–1293PubMedCrossRef

21.

Schneider SA, Hardy J, Bhatia KP (2009) Iron accumulation in syndromes of neurodegeneration with brain iron accumulation 1 and 2: causative or consequential? J Neurol Neurosurg Psychiatry 80:589–590PubMedCrossRef

22.

Koeppen AH, Dickson AC (2001) Iron in the Hallervorden-Spatz syndrome. Pediatr Neurol 25:148–155PubMedCrossRef

23.

Mutoh K, Okuno T, Ito M et al (1988) MR imaging of a group I case of Hallervorden-Spatz disease. J Comput Assist Tomogr 12:851–853PubMedCrossRef

24.

Sethi KD, Adams RJ, Loring DW, Gammal T (1988) Hallervorden-Spatz syndrome: clinical and magnetic resonance imaging correlations. Ann Neurol 24:692–694PubMedCrossRef

25.

McNeill A, Birchall D, Hayflick SJ et al (2008) T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology 70:1614–1619PubMedCrossRef

26.

Lee JH, Kim DS, Baik SK, Nam SO (2010) Nigropallidal iron accumulation in pantothenate kinase-associated neurodegeneration demonstrated by susceptibility-weighted imaging. J Neurol 257:661–662PubMedCrossRef

27.

Hayflick SJ, Penzien JM, Michi W, Sharif UM, Rosman NP, Wheeler PG (2001) Cranial MRI changes may precede symptoms in Hallervorden-Spatz syndrome. Pediatr Neurol 25:166–169PubMedCrossRef

28.

Hayflick SJ, Hartman M, Coryell J, Gitschier J, Rowley H (2006) Brain MRI in Neurodegeneration with brain iron accumulation with and without PANK2 mutations. Am J Neuroradiol 27:1230–1233PubMed

29.

Bruggemann N, Hagenah J, Reetz K et al (2010) Recessively inherited parkinsonism: effect of ATP13A2 mutations on the clinical and neuroimaging data. Arch Neurol 67:1357–1363PubMedCrossRef

30.

Liman J, Wellmer A, Rostasy K, Bahr M, Kermer P (2011) Transcranial ultrasound in neurodegeneration with brain iron accumulation (NBIA). Eur J Paediatr Neurol. doi:10.1016/ejpn.2011.07.009

Title: Transcranial sonography in pantothenate kinase-associated neurodegeneration
Authors: Vladimir S. Kostić
Marina Svetel
Milija Mijajlović
Aleksandra Pavlović
Milica Ječmenica-Lukić
Dušan Kozić
Publication date: 01-05-2012
Publisher: Springer-Verlag
Published in: Journal of Neurology / Issue 5/2012
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-011-6294-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Transcranial sonography in pantothenate kinase-associated neurodegeneration

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2012

Judgment of FLAIR signal change in DWI–FLAIR mismatch determination is a challenge to clinicians

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)-like phenotype: an expanded clinical spectrum of POLG1 mutations

Pure left hippocampal stroke: a transient global amnesia-plus syndrome

Use of intrathecal clonidine in patients with multiple sclerosis or spastic paraparesis

Executive functions are impaired in heterozygote patients with oculopharyngeal muscular dystrophy

Double-blind randomized trial on short-term efficacy of the Semont maneuver for the treatment of posterior canal benign paroxysmal positional vertigo