Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease
The co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient selection for clinical trials. Changes in brain metabolism captured by positron emission tomography (PET) with <sup>18</s...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Tomaž Rus Jernej Mlakar Jan Jamšek Maja Trošt |
| author_facet | Tomaž Rus Jernej Mlakar Jan Jamšek Maja Trošt |
| author_sort | Tomaž Rus |
| collection | DOAJ |
| description | The co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient selection for clinical trials. Changes in brain metabolism captured by positron emission tomography (PET) with <sup>18</sup> F-fluorodeoxyglucose (FDG) allow us to differentiate between different neurodegenerative disorders either by visual exploration or by studying disease-specific metabolic networks in individual patients. However, the impact of multiple proteinopathies on brain metabolism and metabolic networks remains unknown due to the absence of pathological studies. In this case study, we present a 67-year-old patient with rapidly progressing dementia clinically diagnosed with probable sporadic Creutzfeldt–Jakob disease (sCJD). However, in addition to the expected pronounced cortical and subcortical hypometabolism characteristic of sCJD, the brain FDG PET revealed an intriguing finding of unexpected relative hypermetabolism in the bilateral putamina, raising suspicions of coexisting Parkinson’s disease (PD). Additional investigation of disease-specific metabolic brain networks revealed elevated expression of both CJD-related pattern (CJDRP) and PD-related pattern (PDRP) networks. The patient eventually developed akinetic mutism and passed away seven weeks after symptom onset. Neuropathological examination confirmed neuropathological changes consistent with sCJD and the presence of Lewy bodies confirming PD pathology. Additionally, hyperphosphorylated tau and TDP-43 pathology were observed, a combination of four proteinopathies that had not been previously reported. Overall, this case provides valuable insights into the complex interplay of neurodegenerative pathologies and their impact on metabolic brain changes, emphasizing the role of metabolic brain imaging in evaluating potential presence of multiple proteinopathies. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:22:39Z |
| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-81d92d9295f1455bbff05efeb3b992f22023-11-19T08:12:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171308110.3390/ijms241713081Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s DiseaseTomaž Rus0Jernej Mlakar1Jan Jamšek2Maja Trošt3Department of Neurology, University Medical Center Ljubljana, Zaloška cesta 2a, 1000 Ljubljana, SloveniaInstitute of Pathology, Medical Faculty, University of Ljubljana, Korytkova ulica 2, 1000 Ljubljana, SloveniaDepartment of Nuclear Medicine, University Medical Center Ljubljana, Zaloška cesta 7, 1000 Ljubljana, SloveniaDepartment of Neurology, University Medical Center Ljubljana, Zaloška cesta 2a, 1000 Ljubljana, SloveniaThe co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient selection for clinical trials. Changes in brain metabolism captured by positron emission tomography (PET) with <sup>18</sup> F-fluorodeoxyglucose (FDG) allow us to differentiate between different neurodegenerative disorders either by visual exploration or by studying disease-specific metabolic networks in individual patients. However, the impact of multiple proteinopathies on brain metabolism and metabolic networks remains unknown due to the absence of pathological studies. In this case study, we present a 67-year-old patient with rapidly progressing dementia clinically diagnosed with probable sporadic Creutzfeldt–Jakob disease (sCJD). However, in addition to the expected pronounced cortical and subcortical hypometabolism characteristic of sCJD, the brain FDG PET revealed an intriguing finding of unexpected relative hypermetabolism in the bilateral putamina, raising suspicions of coexisting Parkinson’s disease (PD). Additional investigation of disease-specific metabolic brain networks revealed elevated expression of both CJD-related pattern (CJDRP) and PD-related pattern (PDRP) networks. The patient eventually developed akinetic mutism and passed away seven weeks after symptom onset. Neuropathological examination confirmed neuropathological changes consistent with sCJD and the presence of Lewy bodies confirming PD pathology. Additionally, hyperphosphorylated tau and TDP-43 pathology were observed, a combination of four proteinopathies that had not been previously reported. Overall, this case provides valuable insights into the complex interplay of neurodegenerative pathologies and their impact on metabolic brain changes, emphasizing the role of metabolic brain imaging in evaluating potential presence of multiple proteinopathies.https://www.mdpi.com/1422-0067/24/17/13081Creutzfeldt–Jakob diseaseParkinson’s diseasemultiple co-proteinopathyFDG PETbrain networks analysis |
| spellingShingle | Tomaž Rus Jernej Mlakar Jan Jamšek Maja Trošt Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease International Journal of Molecular Sciences Creutzfeldt–Jakob disease Parkinson’s disease multiple co-proteinopathy FDG PET brain networks analysis |
| title | Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease |
| title_full | Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease |
| title_fullStr | Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease |
| title_full_unstemmed | Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease |
| title_short | Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt–Jakob Disease with Concomitant Parkinson’s Disease |
| title_sort | metabolic brain changes can predict the underlying pathology in neurodegenerative brain disorders a case report of sporadic creutzfeldt jakob disease with concomitant parkinson s disease |
| topic | Creutzfeldt–Jakob disease Parkinson’s disease multiple co-proteinopathy FDG PET brain networks analysis |
| url | https://www.mdpi.com/1422-0067/24/17/13081 |
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