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Albadr F, Aldusaymani SM, Aldobikhi YA, Alkhaldi SI, Sendy HS, Aldosari HS, Aljurayyad AS. Creutzfeldt-Jakob Disease in a Saudi Female: A Case Report. Cureus 2024; 16:e75887. [PMID: 39822441 PMCID: PMC11737605 DOI: 10.7759/cureus.75887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/19/2025] Open
Abstract
Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and incurable neurodegenerative disorder caused by prions. It is invariably fatal and classified under transmissible spongiform encephalopathies. This case report presents a 66-year-old Saudi female who was admitted to the neurology department due to a rapidly advancing cognitive decline. The patient underwent diagnostic evaluation, including magnetic resonance imaging (MRI) and electroencephalogram (EEG). Following a month of hospitalization with psychosocial support, the patient was stable and subsequently discharged. In conclusion, while CJD is an uncommon condition, it should be considered in the differential diagnosis of patients presenting with rapidly progressive dementia. Early and accurate diagnosis is essential to differentiate this untreatable disease from other treatable forms of rapidly progressive dementia and to facilitate potential future therapeutic interventions.
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Affiliation(s)
- Fahad Albadr
- Radiology and Medical Imaging, King Saud Medical City, Riyadh, SAU
- Neuroradiology, King Saud University, Riyadh, SAU
| | | | - Yousef A Aldobikhi
- Department of Diagnostic Radiology, King Khalid University Hospital, Riyadh, SAU
| | | | - Hatim S Sendy
- Medicine, Imam Mohammed Ibn Saud University, Riyadh, SAU
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Appel S, Cohen Y, Appel S, Cohen OS, Chapman J, Rosenmann H, Nitsan Z, Kahana E. Sensory disturbances in Creutzfeldt-Jakob disease. Neurol Sci 2024; 45:1057-1062. [PMID: 37828389 DOI: 10.1007/s10072-023-07093-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 09/20/2023] [Indexed: 10/14/2023]
Abstract
BACKGROUND Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.
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Affiliation(s)
- Shmuel Appel
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel.
| | - Yael Cohen
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Shira Appel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Oren S Cohen
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel
| | - Joab Chapman
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Neurology, The Sagol Neuroscience Center, and Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Hanna Rosenmann
- Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Zeev Nitsan
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Esther Kahana
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
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Heo H, Park HY, Suh CH, Shim WH, Lim JS, Lee JH, Kim SJ. Development of statistical auto-segmentation method for diffusion restriction gray matter lesions in patients with newly diagnosed sporadic Creutzfeldt-Jakob disease. Sci Rep 2024; 14:4215. [PMID: 38378772 PMCID: PMC10879176 DOI: 10.1038/s41598-024-51927-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 01/11/2024] [Indexed: 02/22/2024] Open
Abstract
Quantification of diffusion restriction lesions in sporadic Creutzfeldt-Jakob disease (sCJD) may provide information of the disease burden. We aim to develop an automatic segmentation model for sCJD and to evaluate the volume of disease extent as a prognostic marker for overall survival. Fifty-six patients (mean age ± SD, 61.2 ± 9.9 years) were included from February 2000 to July 2020. A threshold-based segmentation was used to obtain abnormal signal intensity masks. Segmented volumes were compared with the visual grade. The Dice similarity coefficient was calculated to measure the similarity between the automatic vs. manual segmentation. Cox proportional hazards regression analysis was performed to evaluate the volume of disease extent as a prognostic marker. The automatic segmentation showed good correlation with the visual grading. The cortical lesion volumes significantly increased as the visual grade aggravated (extensive: 112.9 ± 73.2; moderate: 45.4 ± 30.4; minimal involvement: 29.6 ± 18.1 mm3) (P < 0.001). The deep gray matter lesion volumes were significantly higher for positive than for negative involvement of the deep gray matter (5.6 ± 4.6 mm3 vs. 1.0 ± 1.3 mm3, P < 0.001). The mean Dice similarity coefficients were 0.90 and 0.94 for cortical and deep gray matter lesions, respectively. However, the volume of disease extent was not associated with worse overall survival (cortical extent: P = 0.07; deep gray matter extent: P = 0.12).
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Affiliation(s)
- Hwon Heo
- Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Ho Young Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Chong Hyun Suh
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
| | - Woo Hyun Shim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
| | - Jae-Sung Lim
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae-Hong Lee
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Joon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea
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Safadi D, Cohen OS, Chapman J, Rosenmann H, Nitsan Z, Kahan E, Appel S, Alkrenawi M. The epidemiological and clinical characteristics of patients with young-onset genetic Creutzfeldt-Jakob disease. Neurol Res 2023; 45:854-857. [PMID: 37165675 DOI: 10.1080/01616412.2023.2212210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 05/01/2023] [Indexed: 05/12/2023]
Abstract
OBJECTIVES The onset of Creutzfeldt-Jakob disease (CJD) is usually around the age of 60, but younger patients have been described as well. Our study characterizes the demographic and clinical features of young-onset CJD patients. METHODS The CJD Israeli National Database was reviewed, and the patients were divided into groups of young (<40-year-old) (Y|) and older disease onset (>40-year-old) (O). Each group was further divided into sporadic (sCJD) and genetic (gCJD) patients. Clinical and demographic parameters were compared between the groups. RESULTS The study included 731 patients (Y- 18 patients, O- 713 patients). MRI showed classical features more often in the older population (O-76.9%, Y-36%, p = 0.006). Rapidly progressive dementia as a presenting feature was more common in the older group (O = 58%, Y = 27.7%, p = 0.019) whereas cerebellar onset (gait instability, dysarthria) was more common in the younger group (O = 6.7%, Y = 27.7%, p = 0.036)). Among gCJD patients, rapidly progressive dementia was commonly seen in older patients (O = 54%, Y = 21% p = 0.008) whereas cerebellar symptoms were seen in young patients (O = 7%, Y = 30% p = 0.01) Typical MRI findings were seen in 37% of young people compared to 87% of older patients (p = 0.002). No significant differences were between young and older patients in the sCJD group. CONCLUSION Young-onset gCJD patients have unique disease features including less typical brain MRI changes, a lower prevalence of dementia, and a higher prevalence of cerebellar signs at disease onset.
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Affiliation(s)
- Daniel Safadi
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
| | - Oren S Cohen
- Department of Neurology, Assaf Harofeh Medical Center, Tsrifin, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Joab Chapman
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Neurology, The Sagol Neuroscience Center, and Chaim Sheba Medical Center, Ramat gan
| | - Hanna Rosenmann
- Department of Neurology,The Agnes Ginges Center for Human Neurogenetics, Hadassa Hebrew University Medical Center, Jerusalem, Israel
| | - Zeev Nitsan
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Esther Kahan
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
- Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Shmuel Appel
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
| | - Marwan Alkrenawi
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
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Castelli A, Placidi F, Bonomi CG, Di Giuliano F, Martorana A, Pizzicannella G, Liguori C, Manfredi N, Mari L, Pagano A, Bramato V, Mercuri NB, Izzi F. Periodic sharp wave complexes identify a distinctive phenotype in Creutzfeldt-Jacob disease. Clin Neurophysiol 2022; 143:124-132. [DOI: 10.1016/j.clinph.2022.08.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 08/18/2022] [Accepted: 08/21/2022] [Indexed: 11/03/2022]
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Menendez L, Milo R, Cohen OS, Chapman J, Rosenmann H, Nitsan Z, Kahana E, Appel S. Genetic Creutzfeldt-Jakob disease in Turkish Jews-demographic and clinical features. Acta Neurol Scand 2022; 146:586-589. [PMID: 35974683 DOI: 10.1111/ane.13684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 07/28/2022] [Accepted: 07/31/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND The largest cluster of genetic Creutzfeldt- Jakob Disease (CJD) exists in Libyan Jews carrying the E200K mutation in the PRNP gene. However, there is another cluster of genetic CJD with E200K mutation in families of Turkish-Jewish origin. AIMS In this retrospective study, we aim to describe the demographic and clinical features of this population of patients. MATERIAL AND METHODS The Israeli National CJD database was searched for demographic, clinical, imaging, and laboratory data of genetic CJD patients of Libyan and Turkish ancestry with the E200K mutation. The data of Libyan and Turkish patients were compared with notice similar or different demographic or clinical courses. RESULTS Four hundred and twenty-three patients with CJD of Libyan (L) ancestry and 27 patients with CJD of Turkish (T) ancestry were identified. There were no significant differences in demographic and clinical data between the two populations (age of onset: T = 62 ± 8.8, L = 60 ± 9.7; age of death: T = 63 ± 8.6, L = 61 ± 9.7; and disease duration: T = 7.8 ± 8.4 months, L = 9.6 ± 13.6 months). Rapidly progressive dementia was the most common presentation in both groups, followed by pure cerebellar onset. The levels of tau protein in CSF did not differ between groups (T = 1290 ± 397.6 pg/ml, L = 1276 ± 594.2 pg/ml). MRI and EEG showed classical CJD features in most patients in both groups. DISCUSSION The E200K mutation is the most common mutation among gCJD patients and was reported in different ethnical populations, suggesting several independent haplotypes of the mutation. The Turkish-Jew cluster, first described in this study, shares similar demographic and clinical features with the bigger cluster of Libyan-Jews CJD patients. CONCLUSION E200K gCJD patients of Turkish ancestry share similar demographic and clinical features to patients of Libyan descent, suggesting a common origin of both populations.
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Affiliation(s)
- Leslie Menendez
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel
| | - Ron Milo
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.,Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Oren S Cohen
- Department of Neurology, Assaf Harofeh Medical Center, Zerifin, Israel.,Robert and Martha Harden Chair in Mental and Neurological Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Joab Chapman
- Robert and Martha Harden Chair in Mental and Neurological Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Neurology, The Sagol Neuroscience Center, and Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Hanna Rosenmann
- Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Medical Organization, Faculty of Medicine, Hebrew University, Jerusalem, Israel
| | - Zeev Nitsan
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.,Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Esther Kahana
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.,Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
| | - Shmuel Appel
- Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.,Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
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7
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Trachtenbroit I, Cohen OS, Chapman J, Rosenmann H, Nitsan Z, Kahana E, Appel S. Epidemiological and clinical characteristics of patients with late-onset Creutzfeldt-Jakob disease. Neurol Sci 2022; 43:4275-4279. [DOI: 10.1007/s10072-022-05929-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 02/03/2022] [Indexed: 11/29/2022]
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Xu YW, Wang JQ, Zhang W, Xu SC, Li YX. Rarely fast progressive memory loss diagnosed as Creutzfeldt-Jakob disease: A case report. World J Clin Cases 2021; 9:10638-10644. [PMID: 35004995 PMCID: PMC8686157 DOI: 10.12998/wjcc.v9.i34.10638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 07/18/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Creutzfeldt-Jakob disease (CJD) is a rare degenerative disease of the central nervous system that can be contagious or hereditary and is a rare cause of rapidly progressive dementia. It almost always results in death within 1-2 years from symptom onset.
CASE SUMMARY Here, we report the case of a 57-year-old male who initially experienced dizziness followed by a 1-mo fast decline in memory function. He presented to the local hospital and underwent magnetic resonance imaging and cerebrospinal fluid (CSF) examination, with no definitive diagnosis. However, the symptoms of progressive forgetting worsened. In addition, he exhibited progressive involuntary tremor of the limbs. Then, he came to our hospital, and according to the results of CSF examination, electroencephalography (EEG) and magnetic resonance imaging (MRI) tests and clinical manifestations of cerebellar ataxia, dementia, and myoclonus that rapidly progressed, with a short duration of illness, he was finally diagnosed with sporadic CJD (sCJD).
CONCLUSION This case report aims to create awareness among physicians to emphasize auxiliary examination, CSF examination, EEG and MRI tests and recognition of cerebellar ataxia, dementia, and myoclonus that rapidly progress to prompt pursuit of an early diagnosis and identification of sCJD and to reduce complications.
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Affiliation(s)
- Yong-Wei Xu
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Jie-Qun Wang
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Wei Zhang
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Shu-Chang Xu
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Yun-Xia Li
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
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Park HY, Suh CH, Shim WH, Kim SO, Kim WS, Jeong S, Lee JH, Kim SJ. Prognostic value of diffusion-weighted imaging in patients with newly diagnosed sporadic Creutzfeldt-Jakob disease. Eur Radiol 2021; 32:1941-1950. [PMID: 34842958 DOI: 10.1007/s00330-021-08363-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/21/2021] [Accepted: 09/25/2021] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To evaluate clinico-radiologic markers that predict poor overall survival (OS) in sporadic Creutzfeldt-Jakob disease (sCJD) and to develop a prognostic model. MATERIALS AND METHODS Patients with newly diagnosed sCJD were included who underwent diffusion-weighted imaging (DWI) from February 2000 to July 2020. The impact of 9 clinico-radiologic features on OS was analyzed using univariable and multivariable Cox proportional hazards regression model. The DWI prognostic score model was generated. The weighted kappa was calculated for interobserver agreement. RESULTS Sixty patients (mean age ± SD, 61.0 ± 9.7 years, 32 women) were included. Univariable analysis showed positive associations between poor OS and patient age (p = 0.003), extent of involved cortical lobes (p = 0.11), involvement of caudate nucleus (p = 0.07), and putamen (p = 0.04). Multivariable analysis demonstrated two independent prognostic factors: age ≥ 60 (HR 2.65, 95% CI, 1.41-4.98), and diffusion restriction in caudate nucleus and putamen (HR 2.24, 95% CI, 1.15-4.37). Based on these features, the DWI prognostic score model was generated: low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-5 points) groups. Median OS in high-risk group was 1.7 months, which was significantly shorter than those in the intermediate-risk (14.2 months) and low-risk (26.5 months) groups (p < 0.001). Interobserver agreements were excellent (κ = 0.91-0.92). CONCLUSIONS Our study demonstrated that age and diffusion restriction in caudate nucleus and putamen were the independent prognostic factors of poor overall survival in sporadic Creutzfeldt-Jakob disease. Our DWI prognostic score model may be useful in clinical settings for disease stratification. KEY POINTS • Age ≥ 60, and diffusion restriction in caudate nucleus and putamen were the independent prognostic factors of poor overall survival in sCJD. • Based on our DWI prognostic score model, median overall survival in high-risk group was 1.7 months, which was significantly shorter than those in the intermediate-risk group (14.2 months) and low-risk group (26.5 months) (p < 0.001). • The proposed DWI prognostic score model may be useful in clinical settings for disease stratification.
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Affiliation(s)
- Ho Young Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chong Hyun Suh
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Woo Hyun Shim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seon-Ok Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Woo Seok Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sohee Jeong
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae-Hong Lee
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Joon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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10
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Salehian R, Sina F, Moudi S. Creutzfeldt-Jakob disease: A case report. CASPIAN JOURNAL OF INTERNAL MEDICINE 2021; 12:S359-S362. [PMID: 34760082 PMCID: PMC8559638 DOI: 10.22088/cjim.12.0.359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/25/2019] [Accepted: 07/30/2019] [Indexed: 11/15/2022]
Abstract
Background: Creutzfeldt-Jakob disease (CJD) as a life-threatening neurodegenerative disorder is not usually diagnosed in early stages of the disease because of a variety in its clinical manifestations. This study aimed to present a middle-aged woman with psychiatric symptoms who ultimately was diagnosed as a CJD case. Case presentation: This 48-year-old woman had progressive symptoms of depressed mood, decreased sleep and appetite and mutism which started two months before the first visit. Gradually, slowness in movements, dysarthria and decreased performance were observed. Subsequently, when antidepressant and antipsychotic drugs were prescribed other symptoms such as ataxia and rigidity manifested in the patient. The problem list which led to final confirmation of the disease included non-specific neuropsychological presentations, hypersignality in caudate and putamen areas in brain MRI, generalized high frequency sharp waves in EEG, and protein 14-3-3 identification in cerebrospinal fluid. Conclusion: Although CJD is not a common disease, it should be considered in differential diagnoses whenever neuropsychological manifestations, especially progressive decline in cognition, along with symptoms such as visual hallucinations, myoclonus and ataxia are observed in the patient.
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Affiliation(s)
- Razieh Salehian
- Mental Health Research Center, Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Farzad Sina
- Department of Neurology, Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Sussan Moudi
- Social Determinants of Health Reseach Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
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11
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Soni N, Ora M, Bathla G, Nagaraj C, Boles Ponto LL, Graham MM, Saini J, Menda Y. Multiparametric magnetic resonance imaging and positron emission tomography findings in neurodegenerative diseases: Current status and future directions. Neuroradiol J 2021; 34:263-288. [PMID: 33666110 PMCID: PMC8447818 DOI: 10.1177/1971400921998968] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Neurodegenerative diseases (NDDs) are characterized by progressive neuronal loss, leading to dementia and movement disorders. NDDs broadly include Alzheimer's disease, frontotemporal lobar degeneration, parkinsonian syndromes, and prion diseases. There is an ever-increasing prevalence of mild cognitive impairment and dementia, with an accompanying immense economic impact, prompting efforts aimed at early identification and effective interventions. Neuroimaging is an essential tool for the early diagnosis of NDDs in both clinical and research settings. Structural, functional, and metabolic imaging modalities, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are widely available. They show encouraging results for diagnosis, monitoring, and treatment response evaluation. The current review focuses on the complementary role of various imaging modalities in relation to NDDs, the qualitative and quantitative utility of newer MRI techniques, novel radiopharmaceuticals, and integrated PET/MRI in the setting of NDDs.
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Affiliation(s)
- Neetu Soni
- University of Iowa Hospitals and Clinics, USA
| | - Manish Ora
- Department of Nuclear Medicine, SGPGIMS, India
| | - Girish Bathla
- Neuroradiology Department, University of Iowa Hospitals and
Clinics, USA
| | - Chandana Nagaraj
- Department of Neuro Imaging and Interventional Radiology,
NIMHANS, India
| | | | - Michael M Graham
- Division of Nuclear Medicine, University of Iowa Hospitals and
Clinics, USA
| | - Jitender Saini
- Department of Neuro Imaging and Interventional Radiology,
NIMHANS, India
| | - Yusuf Menda
- University of Iowa Hospitals and Clinics, USA
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12
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Ziukelis ET, Sharma VK, Gome JJ. Premortem diagnosis of pathologically confirmed sporadic Creutzfeldt-Jakob disease. Clin Case Rep 2021; 9:e04461. [PMID: 34322245 PMCID: PMC8299091 DOI: 10.1002/ccr3.4461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 05/21/2021] [Accepted: 05/31/2021] [Indexed: 11/23/2022] Open
Abstract
Sporadic Creutzfeldt-Jakob disease should be considered in any case of rapid neuropsychiatric decline. While neuropathological examination of a brain biopsy specimen remains the only definitive diagnostic method and real-time quaking-induced conversion tests have simplified premortem diagnosis, careful evaluation of magnetic resonance imaging can provide readily accessible clues.
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Affiliation(s)
| | - Vasu Keshav Sharma
- South West HealthcareWarrnamboolVicAustralia
- Health Imaging ServicesWarrnamboolVicAustralia
| | - James J Gome
- South West HealthcareWarrnamboolVicAustralia
- Deakin UniversityBurwoodVicAustralia
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13
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Diagnostic value of diffusion-weighted brain magnetic resonance imaging in patients with sporadic Creutzfeldt-Jakob disease: a systematic review and meta-analysis. Eur Radiol 2021; 31:9073-9085. [PMID: 33982159 DOI: 10.1007/s00330-021-08031-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/14/2021] [Accepted: 04/29/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD). METHODS A systematic literature search of the MEDLINE and EMBASE databases was performed, since their inception up to July 28, 2020. Pooled diagnostic yield of diffusion-weighted imaging was calculated using DerSimonian-Laird random-effects model. Pooled diagnostic performance of DWI (sensitivity, specificity, and area under the curve) in diagnosing sCJD among patients with rapidly progressive dementia was calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed. RESULTS Fifteen original articles with a total of 1144 patients with sCJD were included. The pooled diagnostic yield was 91% (95% confidence interval [CI], 86 to 94%); summary sensitivity, 91% (95% CI, 84 to 95%); and specificity, 97% (95% CI, 94 to 99%). The area under the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI, 0.97-0.99). Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on DWI followed by striatum, thalamus, and cerebellum. Subgroup analysis and meta-regression demonstrated significant heterogeneity among the studies associated with the reference standards used for diagnosis of sCJD. CONCLUSIONS DWI showed excellent diagnostic value in diagnosis of sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia. Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on diffusion-weighted imaging followed by striatum, thalamus, and cerebellum. KEY POINTS • The pooled diagnostic yield of diffusion-weighted imaging in sporadic Creutzfeldt-Jakob disease was 91%. • The diagnostic performance of diffusion-weighted imaging for predicting sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia was excellent, with pooled sensitivity, 91%, and specificity, 97%. • Simultaneous involvement in the neocortex and striatum was most commonly seen on diffusion-weighted imaging (60%), followed by the neocortex without striatum (30%), thalamus (21%), cerebellum (8%), and striatum without neocortex (7%).
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Oldan JD, Jewells VL, Pieper B, Wong TZ. Complete Evaluation of Dementia: PET and MRI Correlation and Diagnosis for the Neuroradiologist. AJNR Am J Neuroradiol 2021; 42:998-1007. [PMID: 33926896 DOI: 10.3174/ajnr.a7079] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Accepted: 11/14/2020] [Indexed: 12/12/2022]
Abstract
This article will familiarize neuroradiologists with the pathophysiology, clinical findings, and standard MR imaging and PET imaging features of multiple forms of dementia as well as new emerging techniques. Cases were compiled from multiple institutions with the goal of improved diagnostic accuracy and improved patient care as well as information about biomarkers on the horizon. Dementia topics addressed include the following: Alzheimer disease, frontotemporal dementia, cerebral amyloid angiopathy, Lewy body dementia, Parkinson disease and Parkinson disease variants, amyotrophic lateral sclerosis, multisystem atrophy, Huntington disease vascular dementia, and Creutzfeldt-Jakob disease.
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Affiliation(s)
- J D Oldan
- From the Department of Radiology (J.D.O., V.L.J), University of North Carolina, Chapel Hill, North Carolina
| | - V L Jewells
- From the Department of Radiology (J.D.O., V.L.J), University of North Carolina, Chapel Hill, North Carolina
| | - B Pieper
- Department of Radiology (B.P.), Richard L. Roudebush VA Medical Center, Indianapolis, Indiana
| | - T Z Wong
- Department of Radiology (T.Z.W.), Duke University Hospital, Durham, North Carolina
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15
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Ascari LM, Rocha SC, Gonçalves PB, Vieira TCRG, Cordeiro Y. Challenges and Advances in Antemortem Diagnosis of Human Transmissible Spongiform Encephalopathies. Front Bioeng Biotechnol 2020; 8:585896. [PMID: 33195151 PMCID: PMC7606880 DOI: 10.3389/fbioe.2020.585896] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 09/28/2020] [Indexed: 12/18/2022] Open
Abstract
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, arise from the structural conversion of the monomeric, cellular prion protein (PrPC) into its multimeric scrapie form (PrPSc). These pathologies comprise a group of intractable, rapidly evolving neurodegenerative diseases. Currently, a definitive diagnosis of TSE relies on the detection of PrPSc and/or the identification of pathognomonic histological features in brain tissue samples, which are usually obtained postmortem or, in rare cases, by brain biopsy (antemortem). Over the past two decades, several paraclinical tests for antemortem diagnosis have been developed to preclude the need for brain samples. Some of these alternative methods have been validated and can provide a probable diagnosis when combined with clinical evaluation. Paraclinical tests include in vitro cell-free conversion techniques, such as the real-time quaking-induced conversion (RT-QuIC), as well as immunoassays, electroencephalography (EEG), and brain bioimaging methods, such as magnetic resonance imaging (MRI), whose importance has increased over the years. PrPSc is the main biomarker in TSEs, and the RT-QuIC assay stands out for its ability to detect PrPSc in cerebrospinal fluid (CSF), olfactory mucosa, and dermatome skin samples with high sensitivity and specificity. Other biochemical biomarkers are the proteins 14-3-3, tau, neuron-specific enolase (NSE), astroglial protein S100B, α-synuclein, and neurofilament light chain protein (NFL), but they are not specific for TSEs. This paper reviews the techniques employed for definite diagnosis, as well as the clinical and paraclinical methods for possible and probable diagnosis, both those in use currently and those no longer employed. We also discuss current criteria, challenges, and perspectives for TSE diagnosis. An early and accurate diagnosis may allow earlier implementation of strategies to delay or stop disease progression.
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Affiliation(s)
- Lucas M. Ascari
- Faculty of Pharmacy, Pharmaceutical Biotechnology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Stephanie C. Rocha
- Faculty of Pharmacy, Pharmaceutical Biotechnology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Priscila B. Gonçalves
- Faculty of Pharmacy, Pharmaceutical Biotechnology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Tuane C. R. G. Vieira
- Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Yraima Cordeiro
- Faculty of Pharmacy, Pharmaceutical Biotechnology Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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16
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Not Just Homeless, Creutzfeldt-Jakob Disease: A Case Report. J Nerv Ment Dis 2020; 208:435-438. [PMID: 32282552 DOI: 10.1097/nmd.0000000000001136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Over a 3-month period, a homeless person was admitted several times to emergency departments after displaying severe behavioral changes and paranoia. No psychiatric tests were performed but all other tests were repeatedly normal; antianxiety treatments or painkillers were the common outcome. It may seem that any diagnosis rested on the patient's immediately apparent social circumstances. Indeed, the patient was admitted to our internal medicine department after a diagnosis of acute delirium within a context of social disadvantage. This social predicament, namely, the patient's evident homelessness, proved to be a false but significant and overarching influence on several misdiagnoses until that moment. Subsequently, actual psychological observations, assessments and tests indicated and confirmed the presence of Creutzfeldt-Jakob disease. Creutzfeldt-Jakob disease is an uncommon and fatal disease; however, early diagnosis can enable the implementation of an important palliative care program. The starkly impoverished social circumstances of a patient should never distract a medical practitioner from a comprehensive diagnosis. Homelessness, for example, may invite certain physical and mental considerations, but it must not overdetermine our response and must not obscure or detract from a wider diagnosis. Homelessness is not a medical condition.
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Appel S, Cohen OS, Chapman J, Gilat S, Rosenmann H, Nitsan Z, Kahan E, Blatt I. The association of quantitative EEG and MRI in Creutzfeldt-Jakob Disease. Acta Neurol Scand 2019; 140:366-371. [PMID: 31393995 DOI: 10.1111/ane.13154] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 07/07/2019] [Accepted: 07/28/2019] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Previous studies showed concordance between the typical Periodic Sharp Wave Complex (PSWC) activity in EEG of Creutzfeldt-Jakob Disease (CJD) patients and the MRI findings, while the concordance with slow activity in EEG is less established. The aim of this study was to better characterize the association between MRI findings and EEG changes using quantitative EEG (qEEG) analysis. METHODS The demographics, clinical features, and the MRI findings of 12 familial E200K patients with CJD were gathered. EEG test was done and reviewed for the typical PSWC and for the non-specific slow activity. A possible association between the MRI findings and the EEG activity was examined. Then, EEG was analyzed using qEEG tool, and the association between the qEEG finding and the MRI was examined. RESULTS Twelve patients were included in the study (67% women). Cortical MRI lesions finding were seen in 6/12 (50%) of the patients, and deep gray mater lesions were seen in 8/12 patients (67%). EEG showed the classic PSWC in 6/12 (50%) of the patients where slow activity was seen in 10/12 (83%). Slow activity and cortical MRI findings were associated in only 2/6 (33%) where deep gray matter findings and the slow activity had concordance of 4/8 (50%). qEEG analysis improved this concordance between slow activity and cortical findings to 3/6 (50%) and with the deep gray matter findings to 5/8 (63%). CONCLUSIONS Quantitative EEG analysis modesty but not significantly, improves the association of EEG slow activity in familial E200K CJD patients with MRI findings.
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Affiliation(s)
- Shmuel Appel
- Department of Neurology Barzilai University Medical Center Ashkelon Israel
- Faculty of Health Sciences Ben Gurion University of the Negev Beer‐Sheva Israel
| | - Oren S. Cohen
- Department of Neurology Assaf Harofeh Medical Center Zerifin Israel
- Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
| | - Joab Chapman
- Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Department of Neurology The Sagol Neuroscience Center, and Chaim Sheba Medical Center Ramat Gan Israel
| | | | - Hanna Rosenmann
- Department of Neurology Hadassah Hebrew University Medical Center Jerusalem Israel
| | - Zeev Nitsan
- Department of Neurology Barzilai University Medical Center Ashkelon Israel
- Faculty of Health Sciences Ben Gurion University of the Negev Beer‐Sheva Israel
| | - Ester Kahan
- Department of Neurology Barzilai University Medical Center Ashkelon Israel
- Faculty of Health Sciences Ben Gurion University of the Negev Beer‐Sheva Israel
| | - Ilan Blatt
- Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Department of Neurology The Sagol Neuroscience Center, and Chaim Sheba Medical Center Ramat Gan Israel
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18
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Canas LS, Sudre CH, De Vita E, Nihat A, Mok TH, Slattery CF, Paterson RW, Foulkes AJM, Hyare H, Cardoso MJ, Thornton J, Schott JM, Barkhof F, Collinge J, Ourselin S, Mead S, Modat M. Prion disease diagnosis using subject-specific imaging biomarkers within a multi-kernel Gaussian process. Neuroimage Clin 2019; 24:102051. [PMID: 31734530 PMCID: PMC6978211 DOI: 10.1016/j.nicl.2019.102051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 09/25/2019] [Accepted: 10/21/2019] [Indexed: 02/01/2023]
Abstract
Prion diseases are a group of rare neurodegenerative conditions characterised by a high rate of progression and highly heterogeneous phenotypes. Whilst the most common form of prion disease occurs sporadically (sporadic Creutzfeldt-Jakob disease, sCJD), other forms are caused by prion protein gene mutations, or exposure to prions in the diet or by medical procedures, such us surgeries. To date, there are no accurate quantitative imaging biomarkers that can be used to predict the future clinical diagnosis of a healthy subject, or to quantify the progression of symptoms over time. Besides, CJD is commonly mistaken for other forms of dementia. Due to the heterogeneity of phenotypes and the lack of a consistent geometrical pattern of disease progression, the approaches used to study other types of neurodegenerative diseases are not satisfactory to capture the progression of human form of prion disease. In this paper, using a tailored framework, we aim to classify and stratify patients with prion disease, according to the severity of their illness. The framework is initialised with the extraction of subject-specific imaging biomarkers. The extracted biomakers are then combined with genetic and demographic information within a Gaussian Process classifier, used to calculate the probability of a subject to be diagnosed with prion disease in the next year. We evaluate the effectiveness of the proposed method in a cohort of patients with inherited and sporadic forms of prion disease. The model has shown to be effective in the prediction of both inherited CJD (92% of accuracy) and sporadic CJD (95% of accuracy). However the model has shown to be less effective when used to stratify the different stages of the disease, in which the average accuracy is 85%, whilst the recall is 59%. Finally, our framework was extended as a differential diagnosis tool to identify both forms of CJD among another neurodegenerative disease. In summary we have developed a novel method for prion disease diagnosis and prediction of clinical onset using multiple sources of features, which may have use in other disorders with heterogeneous imaging features.
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Affiliation(s)
- Liane S Canas
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, United Kingdom.
| | - Carole H Sudre
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, United Kingdom; Dementia Research Centre, UCL Institute of Neurology, 8-11 Queen Square, London, WC1N 3BG, UK
| | - Enrico De Vita
- Institute of Neurology, University College London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, United Kingdom
| | - Akin Nihat
- MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, United Kingdom; NHS National Prion Clinic, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Tze How Mok
- MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, United Kingdom; NHS National Prion Clinic, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Catherine F Slattery
- Dementia Research Centre, UCL Institute of Neurology, 8-11 Queen Square, London, WC1N 3BG, UK
| | - Ross W Paterson
- Dementia Research Centre, UCL Institute of Neurology, 8-11 Queen Square, London, WC1N 3BG, UK
| | - Alexander J M Foulkes
- Dementia Research Centre, UCL Institute of Neurology, 8-11 Queen Square, London, WC1N 3BG, UK
| | - Harpreet Hyare
- NHS National Prion Clinic, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - M Jorge Cardoso
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, United Kingdom
| | - John Thornton
- Institute of Neurology, University College London, United Kingdom
| | - Jonathan M Schott
- Dementia Research Centre, UCL Institute of Neurology, 8-11 Queen Square, London, WC1N 3BG, UK
| | - Frederik Barkhof
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands
| | - John Collinge
- MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, United Kingdom; NHS National Prion Clinic, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Sébastien Ourselin
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, United Kingdom
| | - Simon Mead
- MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, United Kingdom; NHS National Prion Clinic, University College London Hospitals NHS Foundation Trust, London, United Kingdom
| | - Marc Modat
- Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom; School of Biomedical Engineering & Imaging Sciences, King's College London, King's Health Partners, St Thomas' Hospital, London, SE1 7EH, United Kingdom
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Li JSY, Lim KC, Lim WEH, Chen RC. Clinics in diagnostic imaging (193). Sporadic Creutzfeldt-Jakob disease (sCJD). Singapore Med J 2019; 59:634-641. [PMID: 30631881 DOI: 10.11622/smedj.2018146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
A 68-year-old man presented with a three-week history of rapidly progressive dementia, gait ataxia and myoclonus. Subsequent electroencephalography showed periodic sharp wave complexes, and cerebrospinal fluid assay revealed the presence of a 14-3-3 protein. A probable diagnosis of sporadic Creutzfeldt-Jakob disease was made, which was further supported by magnetic resonance (MR) imaging of the brain showing asymmetric signal abnormality in the cerebral cortices and basal ganglia. The aetiology, clinical features, diagnostic criteria, various MR imaging patterns and radiologic differential diagnosis of sporadic Creutzfeldt-Jakob disease are discussed in this article.
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Affiliation(s)
- Jun Si Yuan Li
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
| | - Kheng Choon Lim
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
| | - Winston Eng Hoe Lim
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
| | - Robert Chun Chen
- Department of Diagnostic Radiology, Division of Radiological Sciences, Singapore General Hospital, Singapore
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20
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Heckmann JG, Niedermeier W, Büchner M, Scher B. Distinctive FDG-PET/CT Findings in Acute Neurological Hospital Care. Neurohospitalist 2018; 9:93-99. [PMID: 30915187 DOI: 10.1177/1941874418805339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
A compilation of 6 distinctive 18F-fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) findings in the acute setting of neurohospital care is presented. In case 1, PET/CT allowed the final diagnosis of circumscribed ischemic infarction by demonstrating a clear pattern of luxury perfusion. In case 2, diagnosis of thalamic abscess was made, whereby PET/CT demonstrated an empty zone. Hypermetabolic enlarged hilar lymph nodes and hypermetabolic spinal lumbar roots in PET/CT led to the diagnosis of neurosarcoidosis in case 3. In case 4, a hypermetabolic brain focus in PET/CT identified the seizure focus in epilepsia partialis continua. A cerebral hemispheric hypometabolism in PET/CT in case 5 supported the diagnosis of Creutzfeldt-Jakob disease, which initially mimicked acute stroke. In case 6, PET/CT detected infective endocarditis as a source of multiple cerebral ischemic lesions. In conclusion, PET/CT can contribute importantly to find the correct diagnosis in acute neurohospital patients.
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Affiliation(s)
| | - Wolfgang Niedermeier
- Department of Radiology and Nuclear Medicine, Municipal Hospital Waid, Zurich, Switzerland
| | - Markus Büchner
- Department of Nuclear Medicine, Municipal Hospital Landshut, Germany
| | - Bernhard Scher
- Department of Nuclear Medicine, Municipal Hospital Landshut, Germany
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21
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Abstract
Sporadic Creutzfeldt-Jakob disease (CJD), the most common human prion disease, is generally regarded as a spontaneous neurodegenerative illness, arising either from a spontaneous PRNP somatic mutation or a stochastic PrP structural change. Alternatively, the possibility of an infection from animals or other source remains to be completely ruled out. Sporadic CJD is clinically characterized by rapidly progressive dementia with ataxia, myoclonus, or other neurologic signs and, neuropathologically, by the presence of aggregates of abnormal prion protein, spongiform change, neuronal loss, and gliosis. Despite these common features the disease shows a wide phenotypic variability which was recognized since its early descriptions. In the late 1990s the identification of key molecular determinants of phenotypic expression and the availability of a large series of neuropathologically verified cases led to the characterization of definite clinicopathologic and molecular disease subtypes and to an internationally recognized disease classification. By showing that these disease subtypes correspond to specific agent strain-host genotype combinations, recent transmission studies have confirmed the biologic basis of this classification. The introduction of brain magnetic resonance imaging techniques such as fluid-attenuated inversion recovery and diffusion-weighted imaging sequences and cerebrospinal fluid biomarker assays for the detection of brain-derived proteins as well as real-time quaking-induced conversion assay, allowing the specific detection of prions in accessible biologic fluids and tissues, has significantly contributed to the improved accuracy of the clinical diagnosis of sporadic CJD in recent years.
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Affiliation(s)
- Inga Zerr
- Department of Neurology, University Hospital, Georg-August-University, Goettingen, Germany.
| | - Piero Parchi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna and IRCCS Institute of Neurological Sciences, Bologna, Italy
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Fragoso DC, Gonçalves Filho ALDM, Pacheco FT, Barros BR, Aguiar Littig I, Nunes RH, Maia Júnior ACM, da Rocha AJ. Imaging of Creutzfeldt-Jakob Disease: Imaging Patterns and Their Differential Diagnosis. Radiographics 2017; 37:234-257. [PMID: 28076012 DOI: 10.1148/rg.2017160075] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) remains a challenge because of the large variability of the clinical scenario, especially in its early stages, which may mimic several reversible or treatable disorders. The molecular basis of prion disease, as well as its brain propagation and the pathogenesis of the illness, have become better understood in recent decades. Several reports have listed recognizable clinical features and paraclinical tests to supplement the replicable diagnostic criteria in vivo. Nevertheless, we lack specific data about the differential diagnosis of CJD at imaging, mainly regarding those disorders evolving with similar clinical features (mimicking disorders). This review provides an update on the neuroimaging patterns of sCJD, emphasizing the relevance of magnetic resonance (MR) imaging, summarizing the clinical scenario and molecular basis of the disease, and highlighting clinical, genetic, and imaging correlations in different subtypes of prion diseases. A long list of differential diagnoses produces a comprehensive pictorial review, with the aim of enabling radiologists to identify typical and atypical patterns of sCJD. This review reinforces distinguishable imaging findings and confirms diffusion-weighted imaging (DWI) features as pivotal in the diagnostic workup of sCJD, as these findings enable radiologists to reliably recognize this rare but invariably lethal disease. A probable diagnosis is justified when expected MR imaging patterns are demonstrated and CJD-mimicking disorders are confidently ruled out. ©RSNA, 2017.
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Affiliation(s)
- Diego Cardoso Fragoso
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Augusto Lio da Mota Gonçalves Filho
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Felipe Torres Pacheco
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Bernardo Rodi Barros
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Ingrid Aguiar Littig
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Renato Hoffmann Nunes
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Antônio Carlos Martins Maia Júnior
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
| | - Antonio J da Rocha
- From the Division of Neuroradiology, Serviço de Diagnostico por Imagem, Santa Casa de Misericordia de Sao Paulo, Rua Dr. Cesario Motta Jr. 112, Vila Buarque, Sao Paulo-SP 01221-020, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., B.R.B., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.); and Division of Neuroradiology, Fleury Medicina e Saúde, Sao Paulo, Brazil (D.C.F., A.L.d.M.G.F., F.T.P., I.A.L., R.H.N., A.C.M.M.J., A.J.d.R.)
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High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions. Sci Rep 2017; 7:10655. [PMID: 28878311 PMCID: PMC5587608 DOI: 10.1038/s41598-017-10922-w] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 08/16/2017] [Indexed: 12/14/2022] Open
Abstract
An early and accurate in vivo diagnosis of rapidly progressive dementia remains challenging, despite its critical importance for the outcome of treatable forms, and the formulation of prognosis. Real-Time Quaking-Induced Conversion (RT-QuIC) is an in vitro assay that, for the first time, specifically discriminates patients with prion disease. Here, using cerebrospinal fluid (CSF) samples from 239 patients with definite or probable prion disease and 100 patients with a definite alternative diagnosis, we compared the performance of the first (PQ-CSF) and second generation (IQ-CSF) RT-QuIC assays, and investigated the diagnostic value of IQ-CSF across the broad spectrum of human prions. Our results confirm the high sensitivity of IQ-CSF for detecting human prions with a sub-optimal sensitivity for the sporadic CJD subtypes MM2C and MM2T, and a low sensitivity limited to variant CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. While we found no difference in specificity between PQ-CSF and IQ-CSF, the latter showed a significant improvement in sensitivity, allowing prion detection in about 80% of PQ-CSF negative CJD samples. Our results strongly support the implementation of IQ-CSF in clinical practice. By rapidly confirming or excluding CJD with high accuracy the assay is expected to improve the outcome for patients and their enrollment in therapeutic trials.
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Matías-Guiu JA, Guerrero-Márquez C, Cabrera-Martín MN, Gómez-Pinedo U, Romeral M, Mayo D, Porta-Etessam J, Moreno-Ramos T, Carreras JL, Matías-Guiu J. Amyloid- and FDG-PET in sporadic Creutzfeldt-Jakob disease: Correlation with pathological prion protein in neuropathology. Prion 2017; 11:205-213. [PMID: 28509609 DOI: 10.1080/19336896.2017.1314427] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION The role of positron emission tomography (PET) in Creutzfeldt-Jakob disease is less defined than in other neurodegenerative diseases. We studied the correlation between the uptake of 18F-florbetaben and 18F-fluorodeoxyglucose with pathological prion protein deposition in histopathology in a case. METHODS A patient with 80 y old with a rapid neurological deterioration with a confirmed diagnosis of CJD was studied. PET and MRI studies were performed between 13-20 d before the death. A region of interest analysis was performed using Statistical Parametric Mapping. RESULTS MRI showed atrophy with no other alterations. FDG-PET showed extensive areas of hypometabolism including left frontoparietal lobes as well as bilateral thalamus. Correlation between uptake of 18F-florbetaben and pathological prion protein deposition was r = 0.786 (p < 0.05). Otherwise, correlation between uptake of 18F-FDG and pathological prion protein was r = 0.357 (p = 0.385). Immunohistochemistry with β-amyloid did not show amyloid deposition or neuritic plaques. CONCLUSIONS Our study supports the use of FDG-PET in the assessment of CJD. FDG-PET may be especially useful in cases of suspected CJD and negative MRI. Furthermore, this case report provides more evidence about the behavioral of amyloid tracers, and the possibility of a low-affinity binding to other non-amyloid proteins, such as the pathological prion protein, is discussed.
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Affiliation(s)
- Jordi A Matías-Guiu
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - Carmen Guerrero-Márquez
- b Laboratory of Neuropathology, Brain Bank, Department of Pathology , Hospital Universitario Fundación Alcorcón , Madrid , Spain
| | - María Nieves Cabrera-Martín
- c Department of Nuclear Medicine, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - Ulises Gómez-Pinedo
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain.,d Laboratory of Regenerative Medicine, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - María Romeral
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - Diego Mayo
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - Jesús Porta-Etessam
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - Teresa Moreno-Ramos
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - José Luis Carreras
- c Department of Nuclear Medicine, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
| | - Jorge Matías-Guiu
- a Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC) , Universidad Complutense , Madrid , Spain
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Iaccarino L, Moresco RM, Presotto L, Bugiani O, Iannaccone S, Giaccone G, Tagliavini F, Perani D. An In Vivo 11C-(R)-PK11195 PET and In Vitro Pathology Study of Microglia Activation in Creutzfeldt-Jakob Disease. Mol Neurobiol 2017; 55:2856-2868. [PMID: 28455699 DOI: 10.1007/s12035-017-0522-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 04/06/2017] [Indexed: 01/08/2023]
Abstract
Microgliosis is part of the immunobiology of Creutzfeldt-Jakob disease (CJD). This is the first report using 11C-(R)-PK11195 PET imaging in vivo to measure 18 kDa translocator protein (TSPO) expression, indexing microglia activation, in symptomatic CJD patients, followed by a postmortem neuropathology comparison. One genetic CJD (gCJD) patient, two sporadic CJD (sCJD) patients, one variant CJD (vCJD) patient (mean ± SD age, 47.50 ± 15.95 years), and nine healthy controls (mean ± SD age, 44.00 ± 11.10 years) were included in the study. TSPO binding potentials were estimated using clustering and parametric analyses of reference regions. Statistical comparisons were run at the regional and at the voxel-wise levels. Postmortem evaluation measured scrapie prion protein (PrPSc) immunoreactivity, neuronal loss, spongiosis, astrogliosis, and microgliosis. 11C-(R)-PK11195-PET showed a significant TSPO overexpression at the cortical level in the two sCJD patients, as well as thalamic and cerebellar involvement; very limited parieto-occipital activation in the gCJD case; and significant increases at the subcortical level in the thalamus, basal ganglia, and midbrain and in the cerebellum in the vCJD brain. Along with misfolded prion deposits, neuropathology in all patients revealed neuronal loss, spongiosis and astrogliosis, and a diffuse cerebral and cerebellar microgliosis which was particularly dense in thalamic and basal ganglia structures in the vCJD brain. These findings confirm significant microgliosis in CJD, which was variably modulated in vivo and more diffuse at postmortem evaluation. Thus, TSPO overexpression in microglia activation, topography, and extent can vary in CJD subtypes, as shown in vivo, possibly related to the response to fast apoptotic processes, but reaches a large amount at the final disease course.
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Affiliation(s)
- Leonardo Iaccarino
- Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.,In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy
| | - Rosa Maria Moresco
- Nuclear Medicine Unit, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.,IBFM-CNR, Via F.lli Cervi 93, Segrate, 20090, Milan, Italy.,Department of Health Sciences, University of Milan Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126, Milan, Italy
| | - Luca Presotto
- In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy.,Nuclear Medicine Unit, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy
| | - Orso Bugiani
- IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133, Milan, Italy
| | - Sandro Iannaccone
- Neurological Rehabilitation Unit, Clinical Neurosciences Department, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy
| | - Giorgio Giaccone
- IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133, Milan, Italy
| | - Fabrizio Tagliavini
- IRCCS Foundation "Carlo Besta" Neurological Institute, Via Celoria 11, 20133, Milan, Italy
| | - Daniela Perani
- Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy. .,In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy. .,Nuclear Medicine Unit, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
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Reda HM, Copen WA, Karaa A, Oakley DH. Case 13-2017. A 41-Year-Old Man with Hearing Loss, Seizures, Weakness, and Cognitive Decline. N Engl J Med 2017; 376:1668-1678. [PMID: 28445665 DOI: 10.1056/nejmcpc1616022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Haatem M Reda
- From the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Massachusetts General Hospital, and the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Harvard Medical School - both in Boston
| | - William A Copen
- From the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Massachusetts General Hospital, and the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Harvard Medical School - both in Boston
| | - Amel Karaa
- From the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Massachusetts General Hospital, and the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Harvard Medical School - both in Boston
| | - Derek H Oakley
- From the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Massachusetts General Hospital, and the Departments of Neurology (H.M.R.), Radiology (W.A.C.), Pediatrics (A.K.), and Pathology (D.H.O.), Harvard Medical School - both in Boston
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Prion-specific and surrogate CSF biomarkers in Creutzfeldt-Jakob disease: diagnostic accuracy in relation to molecular subtypes and analysis of neuropathological correlates of p-tau and Aβ42 levels. Acta Neuropathol 2017; 133:559-578. [PMID: 28205010 PMCID: PMC5348556 DOI: 10.1007/s00401-017-1683-0] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/26/2017] [Accepted: 01/29/2017] [Indexed: 01/28/2023]
Abstract
The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrPSc). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82–96%) and virtually full specificity. In the present study, we investigated the diagnostic value of both prion RT-QuIC and surrogate protein markers in a large patient population with suspected CJD and then evaluated the influence on CSF findings of the CJD type, and the associated amyloid-β (Aβ) and tau neuropathology. RT-QuIC showed an overall diagnostic sensitivity of 82.1% and a specificity of 99.4%. However, sensitivity was lower in CJD types linked to abnormal prion protein (PrPSc) type 2 (VV2, MV2K and MM2C) than in typical CJD (MM1). Among surrogate proteins markers (14-3-3, total (t)-tau, and t-tau/phosphorylated (p)-tau ratio) t-tau performed best in terms of both specificity and sensitivity for all sCJD types. Sporadic CJD VV2 and MV2K types demonstrated higher CSF levels of p-tau when compared to other sCJD types and this positively correlated with the amount of tiny tau deposits in brain areas showing spongiform change. CJD patients showed moderately reduced median Aβ42 CSF levels, with 38% of cases having significantly decreased protein levels in the absence of Aβ brain deposits. Our results: (1) support the use of both RT-QuIC and t-tau assays as first line laboratory investigations for the clinical diagnosis of CJD; (2) demonstrate a secondary tauopathy in CJD subtypes VV2 and MV2K, correlating with increased p-tau levels in the CSF and (3) provide novel insight into the issue of the accuracy of CSF p-tau and Aβ42 as markers of brain tauopathy and β-amyloidosis.
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Creutzfeldt-Jakob Disease Mimicking Alzheimer Disease and Dementia With Lewy Bodies-Findings of FDG PET With 3-Dimensional Stereotactic Surface Projection. Clin Nucl Med 2017; 42:e247-e248. [PMID: 28240664 DOI: 10.1097/rlu.0000000000001602] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
A 78-year-old man received a diagnosis of sporadic Creutzfeldt-Jakob disease based on symptoms and findings of MRI, FDG PET, and cerebrospinal fluid markers. PET with 3-dimensional stereotactic surface projection (3D-SSP) showed that the distribution of hypometabolism mimicked that of Alzheimer disease. A 68-year-old woman was treated under a diagnosis of convulsion. Findings of MRI, PET, familial history, and cerebrospinal fluid markers revealed familial Creutzfeldt-Jakob disease. FDG PET with 3D-SSP disclosed that the hypometabolic pattern mimicked that of dementia with Lewy bodies. FDG PET with 3D-SSP can demonstrate similar patterns in various neurodegenerative disorders.
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Cistaro A, Cassalia L, Ferrara C, Atzori C, Vai D, Quartuccio N, Fania P, Vaudano GP, Imperiale D. Brain 18F-FDG PET/CT findings in a case of genetic Creutzfeldt-Jakob disease due to V203I heterozygous mutation in the PRNP gene. J Neurol 2017; 264:170-173. [PMID: 27844164 DOI: 10.1007/s00415-016-8327-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Revised: 10/24/2016] [Accepted: 10/25/2016] [Indexed: 02/07/2023]
Affiliation(s)
- A Cistaro
- Positron Emission Tomography Centre IRMET, S.p.A., Affidea, V. O. Vigliani 89, 10136, Turin, Italy.
| | - L Cassalia
- Nuclear Medicine Unit, Department of Biomedical Sciences and of Mophologic and Functional Images, University of Messina, Messina, Italy
| | - C Ferrara
- Nuclear Medicine Unit Department, P.O. Umberto I, Siracusa, Italy
| | - C Atzori
- Neurology Unit and Human TSE Regional Center, ASL TO2 Maria Vittoria Hospital, Turin, Italy
| | - D Vai
- Neurology Unit and Human TSE Regional Center, ASL TO2 Maria Vittoria Hospital, Turin, Italy
| | - N Quartuccio
- Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK
| | - P Fania
- Positron Emission Tomography Centre IRMET, S.p.A., Affidea, V. O. Vigliani 89, 10136, Turin, Italy
| | - G P Vaudano
- Neuroradiology Unit, ASL TO2 San Giovanni Bosco Hospital, Turin, Italy
| | - D Imperiale
- Neurology Unit and Human TSE Regional Center, ASL TO2 Maria Vittoria Hospital, Turin, Italy
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Multimodality Imaging of Neurodegenerative Processes: Part 2, Atypical Dementias. AJR Am J Roentgenol 2016; 207:883-895. [DOI: 10.2214/ajr.14.12910] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Batra V, Khararjian A, Wheat J, Zhang SX, Crain B, Baras A. From suspected Creutzfeldt-Jakob disease to confirmed histoplasma meningitis. BMJ Case Rep 2016; 2016:bcr-2016-214937. [PMID: 27389723 DOI: 10.1136/bcr-2016-214937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
A 77-year-old man with chronic obstructive lung disease who was on steroids, presented to the hospital after a fall with subacute headaches and ataxia. During the patient's hospital course, his clinical condition deteriorated with myoclonic jerks, fevers and severe encephalopathy. An extensive workup, including EEG, brain MRI and lumbar puncture, revealed possible Creutzfeldt-Jakob disease. Unfortunately, the patient failed to improve and died 12 days after admission. A brain-only autopsy revealed he had acute histoplasma meningitis with patchy superficial cerebritis.
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Affiliation(s)
- Vivek Batra
- Department of Community Physicians, Johns Hopkins, Columbia, Maryland, USA
| | - Armen Khararjian
- Department of Pathology, Johns Hopkins, Baltimore, Maryland, USA
| | | | | | - Barbara Crain
- Department of Pathology, Johns Hopkins, Baltimore, Maryland, USA
| | - Alexander Baras
- Department of Pathology, Johns Hopkins, Baltimore, Maryland, USA
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Manix M, Kalakoti P, Henry M, Thakur J, Menger R, Guthikonda B, Nanda A. Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurg Focus 2015; 39:E2. [DOI: 10.3171/2015.8.focus15328] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%. Several forms of the disease have been described, and the most common is the sporadic type. The most challenging aspect of this disease is its diagnosis—the gold standard for definitive diagnosis is considered to be histopatho-logical confirmation—but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. Imaging studies, electroencephalography, and biomarkers are used in conjunction with the clinical picture to try to make the diagnosis of CJD without brain tissue samples, and all of these are reviewed in this article. The current diagnostic criteria are limited; test sensitivity and specificity varies with the genetics of the disease as well as the clinical stage. Physicians may be unsure of all diagnostic testing available, and may order outdated tests or prematurely request a brain biopsy when the diagnostic workup is incomplete. The authors review CJD, discuss the role of brain biopsy in this patient population, provide a diagnostic pathway for the patient presenting with rapidly progressive dementia, and propose newer diagnostic criteria.
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Quartuccio N, Caobelli F, Evangelista L, Alongi P, Kirienko M, De Biasi V, Cocciolillo F. The role of PET/CT in the evaluation of patients affected by limbic encephalitis: A systematic review of the literature. J Neuroimmunol 2015; 284:44-48. [PMID: 26025057 DOI: 10.1016/j.jneuroim.2015.05.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 05/01/2015] [Indexed: 02/07/2023]
Abstract
Autoimmune limbic encephalitis (LE) is a rare disorder affecting the medial temporal lobe of the brain. Although brain Magnetic Resonance (MR) has been widely evaluated and is currently considered essential in the suspicion of LE, Positron Emission Tomography/Computed Tomography (PET/CT) has been demonstrated to be useful also in the evaluation of brain inflammatory diseases such as encephalitis. We therefore aim to review the current literature about the role of PET/CT in the evaluation of patients affected by LE.
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Affiliation(s)
- Natale Quartuccio
- Nuclear Medicine Unit, Department of Biomedical Sciences and of Morphological and Functional Images, University of Messina, Italy
| | - Federico Caobelli
- Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Germany.
| | - Laura Evangelista
- Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy
| | - Pierpaolo Alongi
- Nuclear Medicine Department, University of Milano-Bicocca, Milan, Italy
| | | | - Vincenzo De Biasi
- Nuclear Medicine Department, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
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