The lack of knowledge about the onset and progression of Parkinson’s disease (PD) hampers its early diagnosis and treatment. Metabolomics might shed light on the PD imprint seeking a broader view of the biochemical remodeling induced by this disease in an early and pre-symptomatic stage and unveiling potential biomarkers. To achieve this goal, we took advantage of the great potential of the European Prospective Study on Nutrition and Cancer (EPIC) cohort to apply metabolomics searching for early diagnostic PD markers. This cohort consisted of healthy volunteers that were followed for around 15 years until June 2011 to ascertain incident PD. For this untargeted metabolomics-based study, baseline preclinical plasma samples of 39 randomly selected individuals that developed PD (Pre-PD group) and the corresponding control group were analyzed using a multiplatform approach. Data were statistically analyzed and exposed alterations in 33 metabolites levels, including significantly lower levels of free fatty acids (FFAs) in the preclinical samples from PD subjects. These results were then validated by adopting a targeted HPLC-QqQ-MS approach. After integrating all the metabolites affected, our finding revealed alterations in FFAs metabolism, mitochondrial dysfunction, oxidative stress, and gut–brain axis dysregulation long before the development of PD hallmarks. Although the biological purpose of these events is still unknown, the remodeled metabolic pathways highlighted in this work might be considered worthy prognostic biomarkers of early prodromal PD. The findings revealed by this work are of inestimable value since this is the first study conducted with samples collected many years before the disease development.

BackgroundParkinson's disease (PD) is a progressive neurodegenerative disorder, diagnosed according to the clinical criteria that occur in already advanced stages of PD. The definition of biomarkers for the early diagnosis of PD represents a challenge that might improve treatment and avoid complications in this disease. Therefore, we propose a set of reliable samples for the identification of altered metabolites to find potential prognostic biomarkers for early PD.MethodsThis case–control study included plasma samples of 12 patients with PD and 21 control subjects, from the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)-Navarra cohort, part of the EPIC-Spain study. All the case samples were provided by healthy volunteers who were followed-up for 15.9 (±4.1) years and developed PD disease later on, after the sample collection. Liquid chromatography coupled to tandem mass spectrometry was used for the analysis of samples.ResultsOut of 40 that were selected and studied due to their involvement in established cases of PD, seven significantly different metabolites between PD cases and healthy control subjects were obtained in this study (benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol, and quinolinic acid). These metabolites are related to mitochondrial dysfunction, the oxidative stress, and the mechanisms of energy production.ConclusionWe propose the samples from the EPIC study as reliable and invaluable samples for the search of early biomarkers of PD. Likewise, this study might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.

No abstract

Cardiac tumors are an infrequent source of embolism to the brain in young adults. Myxomas are the most common among them and they are mainly located in the left atrium.1 Cardiac lipomas are a very rare benign neoplasm of the heart usually located in the right atrium.2,3 Its etiological relationship with stroke is not well established. We describe the case of a thalamic stroke probably caused by paradoxical embolism from a right atrial lipoma through a patent foramen ovale. CASE REPORTA 46-year-old male with mild hypertension, presented with speech and behavioral alterations first noticed on awakening without a previous Valsalva manoeuvre. On admission his blood pressure was 150/90 mm Hg, with a pulse of 70 beats/min and O 2 saturation of 97%. He was apyretic and cardiac and cervical auscultation was unremarkable. On neurologic examination, a non-fluent dysphasia with word finding difficulties, right facial paresis and a left Horner's syndrome was observed. He also presented mild right hemiparesis and myoclonic-dystonic movements in lower limbs (NIHSS 7). Cervical and Transcranial Doppler (TCD) were normal. Cranial computerized tomography was normal. A cranial magnetic resonance (MR) demonstrated on diffusion sequences the presence of an acute non-hemorrhagic infarction involving the anterior area of the left thalamus ( Figure 1A). Perfusion MR sequences and cerebral magnetic angioresonance were normal. The patient was admitted to the stroke unit. Conservative treatment was initiated. No arrhythmia was registered during hospitalization. Duplex sonography excluded atherosclerotic lesions in the carotid arteries. The next day, a right to left massive shunt was found on TCD bubble study ( Figure 1B). This test was performed using agitated saline as a contrast agent. Thrombophilic screening, neoplastic markers and autoimmune assays were negative. Transthoracic and transesophageal echocardiograms (TEE) were performed showing a mobile mass of homogeneous density attached to the free wall of the right atrium ( Figure 1C). No other cardioembolic lesions such as aortic plaques or dysfunctional left ventricle were found. The mass could be optimally assessed by cardiac MR as a well defined, slightly lobulated and homogeneous lesion, strongly hyperintense on T1 sequences, with low signal intensity on Fat-suppressed sequences (T2 STIR) and without contrast enhancement after gadolinium administration ( Figure 1D), highly suggestive of a lipoma. A patent foramen ovale (PFO) without associated aneurysmal septum could also be seen on TEE. The mass and the foramen ovale were surgically removed THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES 379

Background: The identification of biomarkers for the early diagnosis of Parkinson’s Disease (PD) might improve treatment and avoid complications. However, the search of such biomarkers is a real challenge. The main reason for this is that finding samples for that purpose is not an easy task. In this work, we propose a set of reliable samples for the identification of biomarkers for the early diagnosis of PD. In fact, the original source of these samples can be searched for similar purposes when dealing with other diseases.Materials and methods: Case-control study included 12 plasma samples of subjects that subsequently developed PD and 21 plasma samples of matched healthy controls from the Spanish EPIC-Navarra cohort, part of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study. All the case samples were provided by healthy volunteers who were followed up for a mean of 15.9 (± 4.1) years and developed PD disease later on. Therefore, these sample are ideal for the search of early biomarkers of PD. We used an analytical multiplatform based on liquid chromatography and tandem mass spectrometry in order to find significant differences in the amounts of previously reported metabolites that are altered when the disease has been established and diagnosed. Results: Out of all 40 analytes that were studied, seven significant metabolites were observed. Benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol and quinolinic acid were significantly changed in subjects that developed PD. These metabolites are closely related to mitochondrial dysfunction, the oxidative stress and the mechanisms of energy production, which might indicate that these mechanisms are already affected before disease onset.Conclusions: We propose the samples from the EPIC study as reliable and priceless samples for the search of early biomarkers of PD, although many other diseases can be also studied as long as the information stored about the participants recorded such details. As a proof of concept, we showed that these samples were useful for the study of metabolites that may be altered before the participants developed PD. This might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.