Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

M. J. Barrett; J. Hagenah; V. Dhawan; S. Peng; K. Stanley; D. Raymond; A. Deik; S. J. Gross; N. Schreiber-Agus; A. Mirelman; K. Marder; L. J. Ozelius; D. Eidelberg; S. B. Bressman; R. Saunders-Pullman

doi:10.1016/j.parkreldis.2012.09.007

Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

M. J. Barrett^*, J. Hagenah, V. Dhawan, S. Peng, K. Stanley, D. Raymond, A. Deik, S. J. Gross, N. Schreiber-Agus, A. Mirelman, K. Marder, L. J. Ozelius, D. Eidelberg, S. B. Bressman, R. Saunders-Pullman

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Neurologie

24 Zitate (Scopus)

Abstract

Background: Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. Methods: To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [18F]-fluorodeoxyglucose or [18F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. Results: Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [18F]-fluorodeoxyglucose (n = 3) and [18F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. Conclusions: Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.

Originalsprache	Englisch
Zeitschrift	Parkinsonism and Related Disorders
Jahrgang	19
Ausgabenummer	2
Seiten (von - bis)	186-191
Seitenumfang	6
ISSN	1353-8020
DOIs	https://doi.org/10.1016/j.parkreldis.2012.09.007
Publikationsstatus	Veröffentlicht - 01.02.2013

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The research presented in this manuscript was supported by the Empire State Clinical Research Training Program , the Marcled Foundation , and NIH-NINDS NS073836 . LRRK2 and control ultrasound work was supported in part by the Michael J. Fox Foundation. MJB was also supported in part by the CTSA Grant UL1RR025750 , a component of the NIH, and roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or NIH. This study was not industry sponsored. The authors thank all patients and family members who graciously participated in this study; and Akhila Iyer and Jeannie Soto-Valencia for assistance in data collection and recruitment. The LRRK2 Ashkenazi Jewish Consortium includes Karen Marder, Lorraine Clark, Itsik Pe'er, Helen Mejia, Brian Rakitin, Ming-Xin Tang, Roy Alcalay, Tsvyatko Dorovski, Martha Orbe Reilly, Llency Rosado, Elan Louis, Lucien Cote, Cheryl Waters, Blair Ford, Steven Frucht, Stanley Fahn, Oren Levy, and Ernest Roos at Columbia University; Nir Giladi, Avi Orr-Urtreger, Anat Mirelman, Tanya Gurevich, Elissa Ash, Avner Thaler, Shiran Levi, Anat Bar Shira, Mali Gana Weiss, Noa Bregman, Meir Kestenbaum, Talma Hendler, Hedva Lehrman, Einait Even Sapir, Maayan Zelis, Kira Yasinovsky, Anat Shkedy, Arella Hillel, Merav Kedmi, Ziv Gan-Or, Hila Kobo at Tel Aviv University; Susan Bressman, Rachel Saunders-Pullman, Deborah Raymond, Vicki Shanker, Mark Groves, Christina Palmese, Naomi Lubarr, Jeannie Soto-Valencia, Akhila Iyer, Matthew Barrett, Jose Cabassa, Andres Deik, and Ann Hunt at Beth Israel Medical Center; Laurie Ozelius at Mount Sinai School of Medicine; Gary Heiman at Rutgers University; in collaboration with Ken Marek at the Institute for Neurodegenerative Disease; and in collaboration with Caroline Tanner at the Parkinson's Institute. Appendix A

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10.1016/j.parkreldis.2012.09.007

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Barrett, M. J., Hagenah, J., Dhawan, V., Peng, S., Stanley, K., Raymond, D., Deik, A., Gross, S. J., Schreiber-Agus, N., Mirelman, A., Marder, K., Ozelius, L. J., Eidelberg, D., Bressman, S. B., & Saunders-Pullman, R. (2013). Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease. Parkinsonism and Related Disorders, 19(2), 186-191. https://doi.org/10.1016/j.parkreldis.2012.09.007

@article{63ef47524bbc467c8f1857ada33b777f,

title = "Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease",

abstract = "Background: Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. Methods: To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [18F]-fluorodeoxyglucose or [18F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. Results: Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [18F]-fluorodeoxyglucose (n = 3) and [18F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. Conclusions: Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.",

author = "Barrett, \{M. J.\} and J. Hagenah and V. Dhawan and S. Peng and K. Stanley and D. Raymond and A. Deik and Gross, \{S. J.\} and N. Schreiber-Agus and A. Mirelman and K. Marder and Ozelius, \{L. J.\} and D. Eidelberg and Bressman, \{S. B.\} and R. Saunders-Pullman",

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doi = "10.1016/j.parkreldis.2012.09.007",

language = "English",

volume = "19",

pages = "186--191",

journal = "Parkinsonism and Related Disorders",

issn = "1353-8020",

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number = "2",

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Barrett, MJ, Hagenah, J, Dhawan, V, Peng, S, Stanley, K, Raymond, D, Deik, A, Gross, SJ, Schreiber-Agus, N, Mirelman, A, Marder, K, Ozelius, LJ, Eidelberg, D, Bressman, SB & Saunders-Pullman, R 2013, 'Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease', Parkinsonism and Related Disorders, Jg. 19, Nr. 2, S. 186-191. https://doi.org/10.1016/j.parkreldis.2012.09.007

TY - JOUR

T1 - Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

AU - Barrett, M. J.

AU - Hagenah, J.

AU - Dhawan, V.

AU - Peng, S.

AU - Stanley, K.

AU - Raymond, D.

AU - Deik, A.

AU - Gross, S. J.

AU - Schreiber-Agus, N.

AU - Mirelman, A.

AU - Marder, K.

AU - Ozelius, L. J.

AU - Eidelberg, D.

AU - Bressman, S. B.

AU - Saunders-Pullman, R.

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background: Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. Methods: To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [18F]-fluorodeoxyglucose or [18F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. Results: Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [18F]-fluorodeoxyglucose (n = 3) and [18F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. Conclusions: Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.

AB - Background: Heterozygous glucocerebrosidase (GBA) mutations are the leading genetic risk factor for Parkinson disease, yet imaging correlates, particularly transcranial sonography, have not been extensively described. Methods: To determine whether GBA mutation heterozygotes with Parkinson disease demonstrate hyperechogenicity of the substantia nigra, transcranial sonography was performed in Ashkenazi Jewish Parkinson disease subjects, tested for the eight most common Gaucher disease mutations and the LRRK2 G2019S mutation, and in controls. [18F]-fluorodeoxyglucose or [18F]-fluorodopa positron emission tomography is also reported from a subset of Parkinson disease subjects with heterozygous GBA mutations. Results: Parkinson disease subjects with heterozygous GBA mutations (n = 23) had a greater median maximal area of substantia nigral echogenicity compared to controls (n = 34, aSNmax = 0.30 vs. 0.18, p = 0.007). There was no difference in median maximal area of nigral echogenicity between Parkinson disease groups defined by GBA and LRRK2 genotype: GBA heterozygotes; GBA homozygotes/compound heterozygotes (n = 4, aSNmax = 0.27); subjects without LRRK2 or GBA mutations (n = 32, aSNmax = 0.27); LRRK2 heterozygotes/homozygotes without GBA mutations (n = 27, aSNmax = 0.28); and GBA heterozygotes/LRRK2 heterozygotes (n = 4, aSNmax = 0.32, overall p = 0.63). In secondary analyses among Parkinson disease subjects with GBA mutations, maximal area of nigral echogenicity did not differ based on GBA mutation severity or mutation number. [18F]-fluorodeoxyglucose (n = 3) and [18F]-fluorodopa (n = 2) positron emission tomography in Parkinson disease subjects with heterozygous GBA mutations was consistent with findings in idiopathic Parkinson disease. Conclusions: Both transcranial sonography and positron emission tomography are abnormal in GBA mutation associated Parkinson disease, similar to other Parkinson disease subjects.

UR - https://www.scopus.com/pages/publications/84873731061

U2 - 10.1016/j.parkreldis.2012.09.007

DO - 10.1016/j.parkreldis.2012.09.007

M3 - Journal articles

C2 - 23062841

AN - SCOPUS:84873731061

SN - 1353-8020

VL - 19

SP - 186

EP - 191

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

IS - 2

ER -

Transcranial sonography and functional imaging in glucocerebrosidase mutation Parkinson disease

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