Movement disorders: What is the difference between serotonin transporter imaging in multisystem atrophy and Parkinson's disease?

Serotonin dysfunction of the tail brainstem is thought to occur
early in Parkinson's disease (PD).
The relative fragility of these nuclei in Parkinson's disease may be related to their high baseline metabolic activity, or to their critical role in the intercellular transmission of misfolded synaptic proteins in the network of interconnected brainstem projection systems
.
Multisystem atrophy (MSA) is a Parkinson's disease in which neuronal cells are lost
in several neurotransmitter-casting systems.
There are two clinical subtypes of MSA: the Parkinson's subtype (MSA-P), which manifests mainly as Parkinson's disease; The cerebellar subtype (MSA-C), manifested as progressive cerebellar disorder, later manifested as Parkinson's disease
.

Figure 1: Cover art of the paper

MSA is characterized by glial synaptic protein lesions, rather than PD-specific neuronal inclusions
.
In MSA, there is clear neuropathological evidence of serotonin
neurons in the caudal brainstem xialoid nuclear complex.

These neurons are known to project
in the motor and midlateral regions of the brainstem tail and spinal cord.
Their degeneration may contribute to the specific characteristics of MSA, including respiratory and autonomic dysfunction
.

The degree of degradation of MSA's beak serotonin projection system is less
well known than PD.
Beak-like serotonin projection in the striatum, thalamus, and marginal cortex is considered a risk factor
for sleep difficulties, affective symptoms, and weight changes in PD.
Similar non-motor features are also common and severe in MSA, although their biological basis is less clear
.

[11C]3-amino-4-(2-dimethylamino-benzenesulfonyl)-benzonitrile ([11C]DASB) is a positron emission tomography (PET) tracer that, in combination with the serotonin transporter (SERT), quantifies the regional serotonin projection terminal density, providing an opportunity
to examine the endpoint integrity of the beak-like serotonin projection system compared to PD in MSA patients.

In response, Kelvin L.
Chou et al.
of the University of Michigan performed serotonin transporter PET imaging on 18 MSA patients, 23 PD patients, and 16 healthy controls to explore differences in
brainstem, subcortical, and cortically related regions.

Figure 2: Graph of the paper results

They found that MSA patients showed lower serotonin-transporter distribution volume ratios in the medullata, pons, ventral striatum, marginal cortex, and thalamus regions compared with patients
with PD, but no difference
in dorsal striatum, ventral anterior cingulate gyrus, or total cortical regions.

The control group showed greater cortical serotonin transporter binding compared to the PD or MSA group, but lower
serotonin transporter binding in the striatal and other related basal ganglion regions.

There was no regional difference
in binding between patients with the MSA-Parkinson's disease subtype (n = 8) and MSA-cerebellar subtype (n = 10).
The volume ratio of the Serotonin transporter in several different regions was inversely proportional to the severity of the movement score of the Movement Disorders Association of MSA Patients with Movement Disorders Unified Parkinson's Disease Scoring Table, but was not associated
with patients with PD.

The significance of the study was to find that patients with MSA had more severe serotonin deletions in the brainstem and some subcortical regions of the forebrain compared to patients with Parkinson's disease, and showed a specific association with MSA in the severity of movement disorders
.