Introduction

In a paper recently published in Brain a journal of neurology, Horsager et al., investigates two subtypes of Parkinson’s disease (PD) and whether rapid eye movement sleep behavior disorder (RBD) could be a predictive maker of the body-first subtype. The two subtypes differ in where the alpha-synuclien originates. The alpha-synuclein in the brain-first subtype would originate in the brain and make its way to the peripheral nervous system (PNS), whereas the body-first subtype would originate in the PNS and spread to the brain.1 The study supported the existence of brain-first and body-first subtypes of PD with the use of multimodal imaging. The patients who showed signs of RBD correlated to a body-first subtype.¹

Background
Parkinson’s disease is a neurodegenerative disease that affects movement and cognitive functions.² There is no cure for PD but there are treatments to help manage the symptoms. A distinctive feature of PD are Lewy bodies which are misfolded alpha-synuclein proteins that form a toxic clump.^3,4 There is no conclusive reason as to why PD occurs, but one reason could be due to mutations in the SNCA gene. SNCA genes are responsible for making the alpha-synuclein protein, this indicates that PD could be inherited.^4,5 Another component of the study was the RBD, which is characterized by physically and vocally acting out vivid dreams that occur during rapid eye movement (REM) sleep.⁶

Methods
The scientists followed a criteria from the Movement Disorder Society (MDS) to choose 47 Parkinson’s patients between the ages of 50 and 85.¹ There were 13 patients with premotor RBD (PDRBD+), which showed up one year prior to the diagnosis of PD. There were 24 patients without premotor RBD (PDRBD-) who showed no signs of RBD symptoms. These two groups were compared to 22 patients with isolated REM sleep behavior disorder (iRBD). The patients motor, cognitive, and orthostatic hypotension were evaluated. Positron emission tomography (PET) scan and Magnetic resonance imaging (MRI) were performed on all the patients. More specifically, donepezil PET scan was done on the first 20 patients and the following 21 patients had a Siemens Biograph Vision PET/computerized tomography (CT) scan performed. All the patients had I-metaiodobenzylguanidine scrintigraphy to measure cardiac sympathetic innervation and a F-dihydroxyphenylalanine (FDOPA) PET scan to evaluate putaminal dopamine storage capacity.⁷ The images were analyzed blindly to the clinical patient category. All the collected data was graphed onto a scatter plot, so they could be compared to each other to find any correlation.

Results
The standard clinical tests did not indicate any differences between PDRBD+ and PDRBD-, but the data from the multimedia images supported the hypothesis of different PD subtypes.¹ There was a strong correlation when iRBD, PDRBD+, and PDRBD- were all combined together on a correlation graph. The body-first pathway was compatible with the iRBD and PDRBD+ patient data. First there was a loss of cardiac MIBG signal, which was then followed by a loss of putaminal FDOPA signal. The brain-first pathway which correlated to the PDRBD- patient data, had the opposite effect. Brain-first pathway had an initial loss of putaminal FDOPA signal, then a loss of cardiac MIBG signal.

Conclusion
These findings are significant because there is clear evidence that supports two different subtypes for PD. The body-first subtype showed signs of RBD prior to movement abnormalities caused by PD. The two different subtypes seemed to follow different Lewy body pathways. The body-first followed a Braak’s staging pathway. Braak’s staging pathway is when the disease starts from the enteric nervous system (ENS), travels to the brain stem, then travels farther into the brain.⁸ The brain-first contradicted Braak’s staging pathway because it started in the amygdala and traveled down the brain stem into the ENS.⁹ There could be more research done on the two different PD subtypes as they could indicate different causes. Further studies could be done to determine more effective treatment plans for PD patients with different subtypes.

[+] References

[+] Other Work By Tenzin Nordon