Diagnosis of Froin's Syndrome by Parallel Analysis of Ventriculoperitoneal Shunt and Lumbar Cerebrospinal Fluid in a Patient with Cervical Spinal Stenosis.

Elevated protein levels in cerebrospinal fluid (CSF) can occur in various pathologies and are sometimes difficult to interpret. We report a 62-year-old male patient with subacute neurological deterioration, progressive tetraparesis, and cytoalbumin dissociation in the lumbar CSF. The patient had a pre-existing cervical spinal stenosis with mild tetraparesis. Based on the initial cytoalbumin dissociation (protein 938 mg/dL, 4 leucocytes/µL), Guillain-Barré syndrome was initially considered. For further diagnosis, a CSF sample was taken from a pre-existing ventriculoperitoneal shunt, which showed a normal protein and cell count considering the patient's age (protein 70 mg/dL, 1 leucocyte/µL). In conclusion, we suggest that intermediate aggravation of tetraparesis was due to pneumonia with septic constellation, and the cytoalbumin dissociation was interpreted as Froin's syndrome (FS) due to spinal stenosis. In this unique case, we were able to prove the -often suspected- case of FS by parallel analysis of ventriculoperitoneal shunt and lumbar CSF. The triad of xanthochromia, high protein levels, and marked coagulation was first described by Georges Froin and occurs in various processes leading to severe spinal stenosis. The altered composition of lumbar CSF might be due to impaired CSF circulation; however, the exact mechanisms of this phenomenon require further investigation.

Inflammatory CSF profiles and longitudinal development of cognitive decline in sporadic and GBA-associated PD.

Inflammation modifies the incidence and progression of Parkinson's disease (PD). By using 30 inflammatory markers in CSF in 498 people with PD and 67 people with dementia with Lewy bodies (DLB) we show that: (1) levels of ICAM-1, Interleukin-8, MCP-1, MIP-1 beta, SCF and VEGF were associated with clinical scores and neurodegenerative CSF biomarkers (Aß1-42, t-Tau, p181-Tau, NFL and α-synuclein). (2) PD patients with GBA mutations show similar levels of inflammatory markers compared to PD patients without GBA mutations, even when stratified by mutation severity. (3) PD patients who longitudinally developed cognitive impairment during the study had higher levels of TNF-alpha at baseline compared to patients without the development of cognitive impairment. (4) Higher levels of VEGF and MIP-1 beta were associated with a longer duration until the development of cognitive impairment. We conclude that the majority of inflammatory markers is limited in robustly predicting longitudinal trajectories of developing cognitive impairment.

Potential of Non-Coding RNA as Biomarkers for Progressive Supranuclear Palsy.

Objective markers for the neurodegenerative disorder progressive supranuclear palsy (PSP) are needed to provide a timely diagnosis with greater certainty. Non-coding RNA (ncRNA), including microRNA, piwi-interacting RNA, and transfer RNA, are good candidate markers in other neurodegenerative diseases, but have not been investigated in PSP. Therefore, as proof of principle, we sought to identify whether they were dysregulated in matched serum and cerebrospinal fluid (CSF) samples of patients with PSP. Small RNA-seq was undertaken on serum and CSF samples from healthy controls (n = 20) and patients with PSP (n = 31) in two cohorts, with reverse transcription-quantitative PCR (RT-qPCR) to confirm their dysregulation. Using RT-qPCR, we found in serum significant down-regulation in hsa-miR-92a-3p, hsa-miR-626, hsa-piR-31068, and tRNA-ValCAC. In CSF, both hsa-let-7a-5p and hsa-piR-31068 showed significant up-regulation, consistent with their changes observed in the RNA-seq results. Interestingly, we saw no correlation in the expression of hsa-piR-31068 within our matched serum and CSF samples, suggesting there is no common dysregulatory mechanism between the two biofluids. While these changes were in a small cohort of samples, we have provided novel evidence that ncRNA in biofluids could be possible diagnostic biomarkers for PSP and further work will help to expand this potential.

CSF and Serum Levels of Inflammatory Markers in PD: Sparse Correlation, Sex Differences and Association With Neurodegenerative Biomarkers.

Background: An involvement of the central-nervous and peripheral, innate and adaptive immune system in the pathogenesis of Parkinson's disease (PD) is nowadays well established. Objectives: We face several open questions in preparation of clinical trials aiming at disease-modification by targeting the immune system: Do peripheral (blood) inflammatory profiles reflect central (CSF) inflammatory processes? Are blood/CSF inflammatory markers associated with CSF levels of neurodegenerative/PD-specific biomarkers? Methods: Using a multiplex assay we assessed 41 inflammatory markers in CSF/serum pairs in 453 sporadic PD patients. We analyzed CSF/serum correlation as well as associations of inflammatory markers with clinical outcome measures (UPDRS-III, H&Y, MoCA) and with CSF levels of α-synuclein, Aß1-42, t-Tau, p181-Tau and NFL. All analyses were stratified by sex as the immune system shows relevant sex-specific differences. Results: Correlations between CSF and serum were sparse and detected in only 25% (9 out of 36) of the analysable inflammatory markers in male PD patients and in only 38% (12 out of 32) of female PD patients. The most important pro-inflammatory mediators associated with motor and cognitive decline as well as with neurodegenerative/PD-specific biomarkers were FABP, ICAM-1, IL-8, MCP-1, MIP-1-beta, and SCF. Results were more robust for CSF than for serum. Interpretation: Levels of central-nervous and peripheral inflammatory markers might be regulated independently of each other with CSF inflammatory markers reflecting CNS pathology more accurately than peripheral markers. These findings along with sex-specific characteristics have to be considered when designing clinical trials aiming at disease-modification by targeting the immune system.