Zeev Nitsan1,2, Oren S Cohen3,4, Joab Chapman5,4, Esther Kahana6,7, Amos D Korczyn4, Shmuel Appel6,7, Michael Osherov6,7, Hanna Rosenmann8, Ron Milo6,7. 1. Department of Neurology, Barzilai University Medical Center, 2 Hahistadrut St., 7830604, Ashkelon, Israel. zeevn@bmc.gov.il. 2. Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel. zeevn@bmc.gov.il. 3. Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel. 4. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5. Department of Neurology, The Sagol Neuroscience Center, Chaim Sheba Medical Center, Ramat Gan, Israel. 6. Department of Neurology, Barzilai University Medical Center, 2 Hahistadrut St., 7830604, Ashkelon, Israel. 7. Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel. 8. Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Abstract
OBJECTIVE: To characterize the demographic, clinical features and disease course of familial Creutzfeldt-Jakob disease (fCJD) patients homozygous to the E200K mutation. METHODS: The Israeli National CJD Database was screened for patients homozygous to the E200K mutation. Patients' demographic data, clinical presentation and neurological findings, tau protein levels in the cerebrospinal fluid (CSF) and EEG, were assessed. RESULTS: Ten homozygous E200K patients were identified (80% males). Average age of onset was 47.5 ± 6.1 years (range 40-56) and the average age of death was 49.3 ± 7. 7 years (range 42-63) with average disease duration of 27.7 ± 9.7 months (range 2-97). Initial clinical presentation included behavioral change in 4/10 patients, cognitive decline in 3/10 patients and focal neurological deficits in 2/10 patients. Throughout the disease course, the clinical signs in descending order of prevalence included cerebellar (70%), brainstem (60%), extrapyramidal (50%), pyramidal (50%), frontal lobe signs (30%), and disturbances of ocular motility (30%) Compared to the 228 heterozygous E200K fCJD patients, the 10 homozygous patients were significantly younger at disease onset (47.5 vs 59.7 years, p < 0.001), had a longer disease duration (27.7 vs 8.5 months, p < 0.001) and presented more frequently with behavioral changes as initial manifestation (4/10 vs. 34/228, p = 0.05). CONCLUSIONS: Homozygous E200K fCJD patients are characterized by a relatively younger age of onset and longer disease duration. Behavioral changes as a presenting symptom were more common in homozygous patients and cerebellar dysfunction was the most common neurological manifestation throughout the disease course.
OBJECTIVE: To characterize the demographic, clinical features and disease course of familial Creutzfeldt-Jakob disease (fCJD) patients homozygous to the E200K mutation. METHODS: The Israeli National CJD Database was screened for patients homozygous to the E200K mutation. Patients' demographic data, clinical presentation and neurological findings, tau protein levels in the cerebrospinal fluid (CSF) and EEG, were assessed. RESULTS: Ten homozygous E200Kpatients were identified (80% males). Average age of onset was 47.5 ± 6.1 years (range 40-56) and the average age of death was 49.3 ± 7. 7 years (range 42-63) with average disease duration of 27.7 ± 9.7 months (range 2-97). Initial clinical presentation included behavioral change in 4/10 patients, cognitive decline in 3/10 patients and focal neurological deficits in 2/10 patients. Throughout the disease course, the clinical signs in descending order of prevalence included cerebellar (70%), brainstem (60%), extrapyramidal (50%), pyramidal (50%), frontal lobe signs (30%), and disturbances of ocular motility (30%) Compared to the 228 heterozygous E200K fCJD patients, the 10 homozygous patients were significantly younger at disease onset (47.5 vs 59.7 years, p < 0.001), had a longer disease duration (27.7 vs 8.5 months, p < 0.001) and presented more frequently with behavioral changes as initial manifestation (4/10 vs. 34/228, p = 0.05). CONCLUSIONS: Homozygous E200K fCJD patients are characterized by a relatively younger age of onset and longer disease duration. Behavioral changes as a presenting symptom were more common in homozygous patients and cerebellar dysfunction was the most common neurological manifestation throughout the disease course.
Authors: F G Sturtz; P Latour; Y Mocquard; S Cruz; B Fenoll; J M LeFur; D Mabin; G Chazot; A Vandenberghe Journal: Eur Neurol Date: 1997 Impact factor: 1.710
Authors: Teresa Ximelis; Alba Marín-Moreno; Juan Carlos Espinosa; Hasier Eraña; Jorge M Charco; Isabel Hernández; Carmen Riveira; Daniel Alcolea; Eva González-Roca; Iban Aldecoa; Laura Molina-Porcel; Piero Parchi; Marcello Rossi; Joaquín Castilla; Raquel Ruiz-García; Ellen Gelpi; Juan María Torres; Raquel Sánchez-Valle Journal: Alzheimers Res Ther Date: 2021-10-18 Impact factor: 6.982