University of Oulu

Heikkinen, S., Cajanus, A., Katisko, K. et al. Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia. J Neurol 269, 4488–4497 (2022).

Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia

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Author: Heikkinen, Sami1; Cajanus, Antti1; Katisko, Kasper1;
Organizations: 1Institute of Clinical Medicine - Neurology, University of Eastern Finland, P.O. Box 1627 (Yliopistonranta 1C), 70211, Kuopio, Finland
2Neuro Center, Kuopio University Hospital, Kuopio, Finland
3Department of Radiology, Kuopio University Hospital, Kuopio, Finland
4Institute of Clinical Medicine - Radiology, University of Eastern Finland, Kuopio, Finland
5A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
6Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
7MRC, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
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Language: English
Published: Springer Nature, 2022
Publish Date: 2022-09-15


Extrapyramidal (EP) symptoms are a known feature in a subpopulation of patients with behavioral variant frontotemporal dementia (bvFTD). Concomitant EP symptoms with FTD-like neuropsychiatric symptoms are also core features in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). This complicates the early diagnosis of these disorders. Our retrospective register study aimed to discover imaging (MRI and FDG-PET) biomarkers to differentiate PSP, CBD, and bvFTD patients with extrapyramidal symptoms (EP +) from bvFTD patients without EP symptoms (EP-). The records of 2751 patients were screened for the diagnoses and presence of EP symptoms. A total of 222 patients were submitted to imaging analysis and applicable imaging data were recovered from 139 patients. Neuroimaging data were analyzed using Freesurfer software. In the whole cohort, EP + patients showed lower volumes of gray matter compared to EP- patients in the putamen (p = 0.002), bilateral globus pallidum (p = 0.002, p = 0.042), ventral diencephalon (p = 0.002) and brain stem (p < 0.001). In the bvFTD subgroup, there was volumetric difference between EP + and EP− patients in the brain stem. FDG-PET scans in the bvFTD patient subgroup showed that EP + patients had comparative hypometabolism of the superior cerebellar peduncle (SCP) and the frontal lobes. We discovered that EP symptoms are linked to brainstem atrophy in bvFTD patients and the whole cohort. Also, evident hypometabolism in the SCP of bvFTD EP + patients was detected as compared to bvFTD EP− patients. This could indicate that the EP symptoms in these diseases have a more caudal origin in the brainstem than in Parkinson’s disease.

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Series: Journal of neurology
ISSN: 0340-5354
ISSN-E: 1432-1459
ISSN-L: 0340-5354
Volume: 269
Issue: 8
Pages: 4488 - 4497
DOI: 10.1007/s00415-022-11095-x
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Funding: This study has received funding from Finnish Brain Foundation, Finnish Medical Foundation, Finnish Alzheimer’s Disease Research Society, The Finnish Parkinson Foundation, Olvi foundation, Maire Taponen Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Cultural Foundation, Maud Kuistila Memorial Foundation, Instrumentarium Science Foundation, Orion Research Foundation, Sigrid Jusélius Foundation, University of Oulu, Kuopio University Hospital, and Academy of Finland (no. 315459, AH; no. 315460, AMR). Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital.
Academy of Finland Grant Number: 315460
Detailed Information: 315460 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit