Brainstem Atrophy Is Linked to Extrapyramidal Symptoms in Frontotemporal Dementia

Summary: Patients who suffer from frontotemporal dementia with extrapyramidal symptoms have brainstem atrophy and reduced metabolic activity in specific brain regions compared to those with FTD without extrapyramidal symptoms.

Source: University of Eastern Finland

Frontotemporal dementia patients with extrapyramidal symptoms have brainstem atrophy and reduced metabolism in certain areas of the brain significantly more often than patients without extrapyramidal symptoms, a new study from the University of Eastern Finland shows. This observation can facilitate differential diagnostics in frontotemporal dementia.

The findings were published in the Journal of Neurology.

Frontotemporal dementia, FTD, is an umbrella term for degenerative brain diseases that affect behavior and cognition. Sometimes, FTD comes with extrapyramidal symptoms, such as those in Parkinson’s disease, and this makes the diagnosis of FTD challenging.

However, the new study now shows that accurate imaging and analysis of the brain may make it possible to distinguish between FTD and other diseases that cause extrapyramidal symptoms.

Extrapyramidal symptoms refer to involuntary movements, typically tremor, slowness, stiffness, loss of facial expressions and automatic movements, such as arm swing when walking. They are often associated with extrapyramidal disorders such as Parkinson’s disease and atypical parkinsonism.

Examples of atypical parkinsonism include progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). They share disease mechanisms with frontotemporal dementia, which is why they are nowadays considered to be part of the same spectrum of diseases.

Frontotemporal dementia is traditionally divided into two main categories: the more common variant with behavioral changes as an early symptom, and the rarer primary progressive aphasia (PPA) with problems related to speech as an early symptom.

Neurodegeneration associated with progressive memory disorders is typically imaged in two ways: magnetic resonance imaging of the brain provides accurate information on brain structures and volumes of the different parts of the brain, whereas positron emission tomography, or a PET scan, provides information on metabolism in different areas of the brain. Degeneration of the brain tissue is often preceded by slow or missing metabolism.

The researchers analyzed Kuopio University Hospital’s medical records on a total of 139 patients with frontotemporal dementia, PSP or CBD, focusing in particular on their diagnosis and the presence of extrapyramidal symptoms. The patients’ MRI and PET images were analyzed using automated analysis software.

The researchers found that patients with extrapyramidal symptoms also had atrophy of the basal ganglia in the midbrain, and of the brainstem. When looking at patients with frontotemporal dementia alone, it was found that patients with extrapyramidal symptoms had brainstem atrophy considerably more often than patients without extrapyramidal symptoms.

In addition, PET image analyses showed reduced metabolism in the superior cerebellar peduncle and the frontal lobes in patients with extrapyramidal symptoms.

This shows brain scans from the study
Hypometabolism in EP + patients compared to EP− patients in the whole cohort. Orange and yellow colors represent lower metabolism in the EP + group (p < 0.001, uncorrected). Images are presented in neurological orientation (i.e., left hemisphere presented in left side of the picture). Credit: the researchers

The study showed, for the first time, that significant structural and metabolic differences can be detected in the brain of frontotemporal dementia patients with extrapyramidal symptoms, compared to patients without these symptoms.

“If our findings are confirmed in other cohorts, they can be used in early diagnostics to distinguish between frontotemporal dementia and Parkinson’s disease, for example. These findings will also provide us with a better understanding of the mechanisms of these diseases,” says Doctoral Researcher Sami Heikkinen, the lead author of the article.

“Although the treatment of these diseases is symptomatic at the moment, an early and accurate diagnosis is an important step towards the development of disease modifying treatments.”

About this FTD research news

Author: Press Office
Source: University of Eastern Finland
Contact: Press Office – University of Eastern Finland
Image: The image is credited to the researchers

Original Research: Closed access.
Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia” by Sami Heikkinen et al. Journal of Neurology


Brainstem atrophy is linked to extrapyramidal symptoms in frontotemporal dementia

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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