Creutzfeldt-Jakob Disease (CJD), the most notable of the human prion diseases, is invariably fatal. The rarity of CJD, difficulty of early diagnosis, virulent course, and variable modes of transmission, have made clinical studies exceedingly difficult. We here propose a unique method of addressing the difficulties of clinical research in this area. We will use advanced MRI methodology to elucidate early, and even premorbid, cerebral abnormalities of structure and function in such patients. We plan to capitalize on a singular cluster of high incidence occurring among Libyan Jews living in Israel, caused by familial transmission of a mutated prion protein (PrP) gene. Healthy carriers of the relevant mutation (E200K) will be identified (n=50), and will be studied before, as well as after, symptomatic expression. Family members lacking the mutation will serve as controls (n=50). In addition, we will recruit into the study all incident CJD cases in Israel that carry this mutation. We believe we will be able to examine these incident cases within 2 months of onset, and follow them for the duration of the disease. All subjects will have extensive neurological and neuropsychological examinations, as well as MRI, using both traditional structural imaging and newer neuroimaging methods: Diffusion- Weighted Imaging (DWI) and Chemical Shift Imaging (CSI). This project will be the largest neuroimaging study ever conducted in this disease, and the first to observe a genetically homogenous sample. Further, it will provide data on the earliest stages of the disease, including healthy mutation carriers before frank onset of symptomatology. The large sample sizes, availability of healthy mutation carriers, the noncarriers of similar environmental and cultural background, and rapid access to symptomatic patients, are all unprecedented features that should yield definitive data on the early stages of this devastating disease. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS043488-03
Application #
7162153
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Wong, May
Project Start
2005-01-01
Project End
2009-12-31
Budget Start
2007-01-01
Budget End
2009-12-31
Support Year
3
Fiscal Year
2007
Total Cost
$410,819
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Cohen, Oren S; Chapman, Joab; Korczyn, Amos D et al. (2016) Clinical radiological correlation in E200K familial Creutzfeldt-Jakob disease. J Neural Transm (Vienna) 123:1457-1462
Givaty, Gili; Maggio, Nicola; Cohen, Oren S et al. (2016) Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease. J Sleep Res 25:571-575
Cohen, O S; Kimiagar, I; Korczyn, A D et al. (2016) Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease. Eur J Neurol 23:871-7
Cohen, Oren S; Chapman, Joab; Korczyn, Amos D et al. (2015) Characterization of sleep disorders in patients with E200K familial Creutzfeldt-Jakob disease. J Neurol 262:443-50
Appel, S; Chapman, J; Cohen, O S et al. (2015) Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease. Acta Neurol Scand 131:152-7
Cohen, Oren S; Chapman, Joab; Korczyn, Amos D et al. (2015) Familial Creutzfeldt-Jakob disease with the E200K mutation: longitudinal neuroimaging from asymptomatic to symptomatic CJD. J Neurol 262:604-13
Lee, H; Cohen, O S; Rosenmann, H et al. (2012) Cerebral white matter disruption in Creutzfeldt-Jakob disease. AJNR Am J Neuroradiol 33:1945-50
Appel, Shmuel A; Chapman, Joab; Prohovnik, Isak et al. (2012) The EEG in E200K familial CJD: relation to MRI patterns. J Neurol 259:491-6
Cohen, Oren S; Prohovnik, Isak; Korczyn, Amos D et al. (2012) Characterization of movement disorders in patients with familial Creutzfeldt-Jakob disease carrying the E200K mutation. Isr Med Assoc J 14:162-5
Cohen, O S; Prohovnik, I; Korczyn, A D et al. (2011) The Creutzfeldt-Jakob disease (CJD) neurological status scale: a new tool for evaluation of disease severity and progression. Acta Neurol Scand 124:368-74

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