New research on Lewy bodies, Pisa syndrome, and changes in the gut

New research showing improved visualization of Lewy bodies, structural brain changes in Pisa syndrome, and changes in inflammatory markers, the colonic mucosal barrier and fecal microbiota in Parkinson’s disease was presented at a Movement Disorders oral presentation at EAN 2022.

Three-dimensional visualization of Lewy bodies1

Improved three-dimensional visualization of Lewy bodies might reveal new therapeutic targets

A deeper understanding of the structure of the characteristic alpha-synuclein aggregates (Lewy bodies) in the substantia nigra in Parkinson’s disease might inform the development of new therapeutic targets. However, conventional imaging techniques such as histology and electron microscopy do not provide sufficient three-dimensional information, and magnetic resonance imaging and computed tomography lack spatial resolution.

Dr Eva Sole Cruz, Grenoble, France, and colleagues therefore assessed the ability of multiscale synchrotron phase contrast X-ray imaging (S-PCI) for visualizing Lewy bodies in the substantia nigra of four deceased donors. They found that multiscale S-PCI was non-inferior compared with histology but provided the three-dimensional views not previously available for further investigation.1

 

Pathogenesis of Pisa syndrome

Pisa syndrome — a reversible lateral bending of the trunk with a tendency to lean to one side — is a common and disabling symptom of PD.2 The pathogenesis is unknown.

Right angular gyrus hypometabolism was seen in Pisa syndrome patients and was present from PD diagnosis

To investigate this further, Dr Erica Biassoni, Genoa, Italy, and colleagues compared dopamine transporter single-photon emission computed tomography (DaT-SPECT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) images from patients with PD who later developed Pisa syndrome. The patients were divided into right and left subgroups based on the side of the lean. The DaT-SPECT images were then compared with those of PD patients without Pisa syndrome, and the FDG-PET images were compared with those of healthy controls.

The group found no significant differences between the DaT-SPECT and FDG-PET images between the right and left subgroups or in DaT-SPECT images between patients with PD with and without Pisa syndrome.

However, all Pisa syndrome patients showed right angular gyrus hypometabolism, which was present from the time of PD diagnosis.3

 

Inflammatory markers, the colonic mucosal barrier and fecal microbiota in Parkinson’s disease

Compared with controls, patients with PD have increased permeability of the gut barrier, colonic mucosal barrier remodelling and changes in gut microbiota composition

Dr Gabriele Bellini, Pisa, Italy, and colleagues investigated changes in the intestinal epithelial barrier and inflammatory responses in 19 patients with PD and 19 healthy controls.

They measured plasma lipopolysaccharide binding protein (LBP) and interleukin-1 beta (IL-1beta) and stool IL-1beta and tumor necrosis factor (TNF), and analyzed the gut microbiota. They also evaluated colonic biopsies for epithelial mucins, collagen fibers, claudin-1 and S-100-positive glial cells.

Compared with the healthy controls, the patients with PD showed:

  • Significant increases in plasma LBP, fecal TNF and IL-1beta levels
  • Elevated expression of acidic mucins, collagen fibers and S-100 positive glial cells, and a decrease in neutral mucins and claudin-1 expression in colonic biopsies
  • A significant difference in fecal microbiota alpha-diversity
  • No differences in fecal microbiota beta-diversity

Are the changes in the gut of patients with PD relevant to PD pathogenesis or a consequence of the disease?

Further studies are now needed to investigate whether these differences indicating increased permeability of the gut barrier and colonic mucosal barrier remodelling, together with changes in gut microbiota composition are relevant in PD pathogenesis or are a consequence of the disease.4

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References
  1. Sole Cruz E, Fourneier M, De Schlichting E, et al. 3D visualization of Lewy bodies: Insight into Parkinsonian’s substantia nigra using synchrotron phase-contrast imaging. Eur J Neurol. 2022;29 (Suppl. 1):93–4.
  2. Barone P, Santangelo G, Amboni M, Pellecchia MT, Vitale C. Pisa syndrome in Parkinson’s disease and parkinsonism: clinical features, pathophysiology, and treatment. Lancet Neurol. 2016;15(10):1063–74.
  3. Biassoni E, Kreshpa W, Mattioli P, et al. Neuroimaging evidence for a body schema disorder in Pisa syndrome of Parkinson’s disease. Eur J Neurol. 2022;29 (Suppl. 1):94.
  4. Bellini G, Frosini D, Benvenuti L, et al. Intestinal histomorphological and molecular alterations in patients with Parkinson’s disease: results from a pilot study. Eur J Neurol. 2022;29 (Suppl. 1):95–6.
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