Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Blevins, G.
Right arrow Articles by Donat, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blevins, G.
Right arrow Articles by Donat, J. R.
Related Collections
Right arrow All Cerebrovascular disease/Stroke
Right arrow Infarction
Right arrow Stroke in young adults
Right arrow All Cognitive Disorders/Dementia
Right arrow Alzheimer's disease

Neurology 2003;60:1625-1630
© 2003 American Academy of Neurology

Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His

G. Blevins, MD FRCPC, R. Macaulay, MD FRCPC, S. Harder, MD FRCPC, D. Fladeland, MD FRCPC, T. Yamashita, MD PhD, M. Yazaki, MD PhD, K. Hamidi Asl, MD, M. D. Benson, MD and J. R. Donat, MD FRCPC

From the Neuroimmunology Branch (Dr. Blevins), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Department of Pathology (Dr. Macaulay), QE II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada; Department of Medical Imaging (Drs. Harder and Fladeland) and Division of Neurology (Dr. Donat), Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Department of Pathology & Laboratory Medicine (Drs. Yamashita, Yazaki, and Benson, and K. Hamidi Asl), Indiana University School of Medicine, Indianapolis; and Richard L. Roudebush Veterans Affairs Medical Center (Dr. Benson), Indianapolis, IN.

Address correspondence and reprint requests to Dr. J.R. Donat, Division of Neurology, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada, S7N 0W8; e-mail: donatj{at}sdh.sk.ca

Objective: To describe the clinical, radiologic, and pathologic findings of a kindred with oculoleptomeningeal amyloidosis and a newly associated transthyretin mutation.

Background: Transthyretin (TTR) amyloidosis can present in the form of oculoleptomeningeal amyloidosis. Clinical features include dementia, seizures, stroke-like episodes, subarachnoid hemorrhage, ataxia, myelopathy, deafness, radiculopathy, and ocular amyloidosis. Eight TTR mutations associated with oculoleptomeningeal amyloidosis have been described.

Methods: Fourteen individuals from a kindred with oculoleptomeningeal amyloidosis were examined clinically and radiologically. Analysis of the TTR gene was performed. Neuropathologic examination was obtained on the index patient.

Results: Affected individuals had vitreous amyloid, radiculopathy, seizures, stroke-like episodes, encephalopathy, and dementia. Severely affected individuals died by the end of the fifth decade. Leptomeningeal enhancement on contrast MRI and elevated CSF protein were the defining features on investigations. Sequencing of exon 3 in the TTR gene found a base pair substitution at codon 69. This resulted in heterozygosity for normal tyrosine and variant histidine (ATTR Tyr69His) in affected family members. Domino liver transplantation was attempted as treatment for one family member.

Conclusions: The ATTR Tyr69His mutation is associated with oculoleptomeningeal amyloidosis. Expression of the genotype is variable. This has implications for treatment of affected individuals and counseling of family members. Efficacy of liver transplantation in patients with oculoleptomeningeal amyloidosis remains unknown. The authors advocate the investigation of liver transplantation in patients with severe symptoms due to oculoleptomeningeal amyloidosis.




This article has been cited by other articles:


Home page
 NeurologyHome page
T. Yamashita, Y. Ando, M. Ueda, M. Nakamura, S. Okamoto, M. E. Zeledon, T. Hirahara, T. Hirai, A. Ueda, Y. Misumi, et al.
Effect of liver transplantation on transthyretin Tyr114Cys-related cerebral amyloid angiopathy
Neurology, January 8, 2008; 70(2): 123 - 128.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
C Douglass, K Suvarna, M M Reilly, P N Hawkins, and M Hadjivassiliou
A novel amyloidogenic transthyretin variant, Gly53Ala, associated with intermittent headaches and ataxia
J. Neurol. Neurosurg. Psychiatry, February 1, 2007; 78(2): 193 - 195.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. D. Dowell, J. D. Fleck, S. T. Vakili, and M. D. Benson
Familial oculoleptomeningeal amyloidosis associated with primary angiitis of the CNS
Neurology, January 2, 2007; 68(1): 77 - 78.
[Full Text] [PDF]

Home page
 NeurologyHome page
M. Nakamura, T. Yamashita, M. Ueda, K. Obayashi, T. Sato, T. Ikeda, Y. Washimi, T. Hirai, Y. Kuwahara, M. T. Yamamoto, et al.
Neuroradiologic and clinicopathologic features of oculoleptomeningeal type amyloidosis
Neurology, October 11, 2005; 65(7): 1051 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
K Jin, S Sato, T Takahashi, H Nakazaki, Y Date, M Nakazato, T Tominaga, Y Itoyama, and S Ikeda
Familial leptomeningeal amyloidosis with a transthyretin variant Asp18Gly representing repeated subarachnoid haemorrhages with superficial siderosis
J. Neurol. Neurosurg. Psychiatry, October 1, 2004; 75(10): 1463 - 1466.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by AAN Enterprises, Inc.