Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor.

Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.

Proteomic Analysis of the Cerebrospinal Fluid in Patients With Essential Tremor Before and After Deep Brain Stimulation Surgery: A Pilot Study.

OBJECTIVE: Electrical neuromodulation by deep brain stimulation (DBS) is a well-established method for treatment of severe essential tremor (ET). The mechanism behind the tremor relieving effect remains largely unknown. Our aim of this study was to evaluate alterations in proteomics pre- and post-DBS in patients diagnosed with severe ET. MATERIALS AND METHODS: Ten right-handed ET patients were included in this study. Cerebrospinal fluid (CSF) was obtained by lumbar puncture preoperatively (N = 10) and six months postoperatively (N = 7). The samples were analyzed by high sensitive liquid chromatography tandem mass spectrometry. RESULTS: Twenty-two proteins were statistically significantly altered in the CSF of ET patients before and after DBS treatment. Downregulated proteins were involved in regulatory processes of protein activation, complement activation, humoral immune response as well as acute inflammatory response. The upregulated proteins were involved in pathways for cell secretion, adhesion as well as response to axon injury. CONCLUSIONS: DBS in ET patients effects the neurochemical environment in the CSF. These findings further elucidate the mechanisms of DBS and may lead to new biomarkers for evaluating the effect of DBS treatment.

Essential tremor: from bedside to bench and back to bedside.

PURPOSE OF REVIEW: The last several years have witnessed a remarkable increase in research on essential tremor, with consequent advances in our understanding of this entity. An attempt to both summarize and frame this work has not been undertaken. RECENT FINDINGS: Here, I show that observations on essential tremor arising from clinical practice/clinical studies have guided scientific studies of this disorder. In turn, the results of scientific studies are beginning to be translated back to the bedside to improve treatment. Recent essential tremor research has given rise to several novel and intriguing ideas about the disease. These include the following: essential tremor may represent a family of diseases rather than a single disease; essential tremor seems to be a disease of the cerebellum or cerebellar system; essential tremor may be neurodegenerative; low gamma aminobutyric acid tone seems to be a central feature of essential tremor. As with many emerging ideas, there is significant discussion and debate over these emerging ideas, and this fuels additional scientific studies. SUMMARY: The flow of ideas from clinical observations about essential tremor, to their translation into scientific studies, and their translation back to the bedside, is expected to eventually lead to improvements at the patient interface.

Cytotoxicity of ventricular cerebrospinal fluid from Parkinson patients: correlation with clinical profiles and neurochemistry.

Other investigators have reported that the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) might contain endogenous dystrophic factors. Using CSF samples drawn from individual PD patients during surgery, we investigated the toxic effect of ventricular CSF (vCSF) on the growth of PC12 cells and the correlation between the clinical profiles of the patients and CSF neurochemistry. Ventricular CSF samples from 28 patients with PD or essential tremor (ET) were collected during ventriculography for stereotactic pallidotomy or thalamotomy. PC12 cells were incubated with 20% vCSF from both clinical groups for up to 72 h. Microdialysis was used to analyze four neurochemical parameters (glucose, lactate, pyruvate, and glutamate) in each vCSF sample. We observed that vCSF drawn from PD patients exerted nonspecific growth inhibition on PC12 cells in a time-dependent manner. The growth inhibitory action of PD-vCSF decreased significantly after heat treatment. Microdialysis demonstrated no statistical differences between PD and ET samples among the four parameters studied. In addition, PC12 cell survival after 72 h incubation with PD-vCSF correlated with no neurochemical parameter or individual clinical profile (age, onset age, duration of disease, Hoehn & Yahr stage, disease progression rate), except for a slight correlation between vCSF and disease progression rate in heat treated samples from female patients. One or more endogenous cytotoxic factors in PD-vCSF inhibit PC12 cell growth. This factor or factors are partially sensitive to heat which suggests proteins or peptides as possible agents. The cytotoxic effect of PD-vCSF did not directly correlate with any clinical profiles studied or energy metabolism of PD brain.