Acta Neurologica Scandinavia: Inflammation and fatigue in early, untreated Parkinson's Disease - by Herlofson et al - 2019

Inflammation and fatigue in early, untreated Parkinson's Disease

Abstract
Objectives
Parkinson's disease (PD)‐related fatigue is a significant clinical problem, and the pathological processes that cause fatigue remain unknown. The aim of the present study was to explore the possible association of peripheral inflammation markers and fatigue in PD.

Materials & methods
We included 47 drug naïve, newly diagnosed PD patients with low (≤3.0) or high (>5.5) fatigue levels as evaluated by the Fatigue Severity Scale (FSS). Strict diagnostic criteria were applied for inclusion. Patients with possible confounding causes for fatigue were excluded. Serum concentrations of a panel of inflammatory markers (IL‐8, TNF‐α, MCP1, MIP‐1β, IL‐6, IL‐6R, p‐selectin, E‐selectin‐1, ICAM, VCAM‐1, CCL5, IL1‐Ra, and TNFR1) were measured using ELISA technology in PD patients with and without fatigue to assess the potential relationships of fatigue in newly diagnosed, treatment‐naïve patients.

Results
Fatigued PD patients had significantly higher levels of the IL‐1 receptor antagonist (IL1‐Ra) (1790 pg/mL (SD1007) vs 1262 pg/mL (SD379)) and of the adhesion molecule VCAM 1 (1071 ng/mL (SD276) vs 895 ng/mL (SD229)) than non‐fatigued patients. A binary logistic regression model, including high or low FSS score as the dependent variable and UPDRS motor score, MADRS, MMSE, ESS, and IL1‐Ra/VCAM‐1 as independent variables, showed a significant effect both for IL1‐Ra and VCAM‐1.

Conclusions
Higher serum levels of the inflammatory molecules IL1‐Ra and VCAM‐1 were associated with higher fatigue levels in patients with newly diagnosed, drug‐naïve PD. These findings highlight an altered immune response as a potential contributor to PD‐related fatigue, from the earliest clinical stages of the disease.

 

Article about the study in ScienceDaily from August 9th.
Biomarkers link fatigue in cancer, Parkinson's

The researchers hope the discovery will allow health care providers to target specific treatments that can lower the levels of the inflammatory biomarkers and in turn improve the quality of life for the patients impacted.

"This discovery may help health professionals to develop treatments that target the biological mechanisms underlying fatigue," Fagundes said. "By targeting the biological mechanism rather than simply teaching patients how to cope with the symptoms, we could potentially alleviate fatigue in these patients."

 

I recognise one of the authors, prof. and neurologist Ole-Bjørn Tysnes from the CFS/ME literature. He has co authored the article Investigation of suspected chronic fatigue syndrome/myalgic encephalopathy which showed that many patients referred to the neurological department at Haukeland university hospital for CFS/ME assessment turned out to suffer from other conditions instead.

A total of 48 patients (13.2 %) were diagnosed with CFS/ME, while a further 18 patients (4.9 %) were diagnosed with post-infectious fatigue. Mental and behavioural disorders were diagnosed in 169 patients (46.3 %), and these represented by far the largest group. Serious, but unrecognised somatic illness was discovered in two patients, while changes of uncertain significance were identified by MRI and lumbar puncture in a few patients.

He is a proponent for a psychosocial explanatory model for CFS/ME, and I'm afraid that might reduce the chances for the researchers to look into possible connections with fatigue in patients with cancer or Parkinson's disease with fatigue in ME patients.

Edited for clarity.

 

The result looks hard to interpret. They measured 13 'markers of inflammation' and found two raised, one of which is actually an anti-inflammatory molecule and the other an adhesion molecule that has no very obvious significance in the absence of inflammatory signals to raise it (TNF, IL-6 ).

 

Cell adhesion molecules

BMJ. 1999 Aug 7; 319(7206): 332–334.
doi: 10.1136/bmj.319.7206.332

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1126974/