Objective: To investigate cerebrospinal fluid (CSF) markers of neurodegeneration [neurofilament light chain (NFL), total Tau (T-Tau)], tau pathology [phosphorylated tau (p-Tau)], glial cell damage or activation [glial fibrillary acidic protein (GFAP)], and brain amyloidosis [β-amyloid 1-42 (Aβ42)] ), and their relationship to key clinical milestones in patients with advanced Parkinson´s disease (PD) operated at our center with STN-DBS for at least 15 years ago.

Background: The diagnostic potential of CSF protein biomarkers has been intensely investigated during the last years, particularly in early PD. CSF T-Tau, p-Tau, Aβ42, and α-synuclein have been reported as slightly lower in early PD compared with healthy controls. A substantial number of advanced PD-patients are treated with deep brain stimulation (DBS) commonly targeting the subthalamic nucleus (STN) or globus pallidus interna (GPi). There are few data on CSF protein markers in this subpopulation.

Methods: Retrospective analysis of available CSF and clinical data in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with subthalamic nucleus deep brain stimulation (STN-DBS) at Sahlgrenska University Hospital before January 1, 2001, were regularly assessed until January 10, 2018, or until death, or until lost to follow-up.

Results: Twenty three PD patients were operated with STN-DBS. Sixteen of these (six females and ten males) underwent at least one lumbar puncture immediately prior to or after STN-DBS. Their age at the latest available LP was 64 (55-75) years [median (range)], PD duration 20 (11 – 33) years, and Hoehn & Yahr stage 3 (2 – 4). Time between DBS operation and the last LP was 4.5 (0.3-10.8) years. Time from the last LP to the last follow up was 6 (0.1-18) years, and for the entire cohort 115 person-years. On January 10, 2018, four PD-patients (25 %) were still alive. All preoperative CSF marker levels were normal. Between two days and six months after DBS, NFL and GFAP levels increased sharply but they normalized thereafter in most patients, and were normal up to almost 11 years after neurosurgery. Over time, all patients deteriorated slowly. At the last follow up, H&Y was 5 (3-5) and 12/16 were demented. There was no significant correlation between postoperative (> 6 months) CSF NFL, GFAP, T-Tau, p-Tau, β-amyloid levels and the presence of dementia, psychosis, inability to walk or need for nursing home at the time for LP, nor for presence of dementia at the last follow up or for death as of January 10, 2018.

Conclusions: CSF protein biomarkers remain normal despite long PD duration, severe disability, and chronic STN-DBS. They cannot be used for PD staging or prognostication but may indicate brain damage caused by other pathological factors.

References: Mollenhauer B, Zimmermann J, Sixel-Doring F, Focke NK, Wicke T, Ebentheuer J, et al. Monitoring of 30 marker candidates in early Parkinson disease as progression markers. Neurology. 2016;87(2):168-77. Hall S, Ohrfelt A, Constantinescu R, Andreasson U, Surova Y, Bostrom F, et al. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol. 2012;69(11):1445-52.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-protein-biomarkers-in-pd-patients-after-dbs-stn-surgery-a-retrospective-analysis-of-patients-that-underwent-surgery-between-1993-and-2001/