Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain-Barré syndrome.

Multiple sclerosis (MS) and Guillain-Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

The effect of psychiatric comorbidities and stress-coping strategies on perceived quality of life in migraine.

BACKGROUND AND PURPOSE: Migraine is one of the most disabling primary headache conditions. We aimed to detect hidden symptoms of anxiety and depression and to survey stress-coping mechanisms and related quality of life in a large migraine population without any known psychiatric comorbidity. METHODS: 123 migraine patients (MG) and 66 healthy subjects (HC) completed the Beck Depression Inventory-II (BDI-II), the State and Trait Anxiety Inventory (S-STAI and T-STAI), the Stress and Coping Inventory (SCI) and the 36-Item Short Form Health Survey (SF-36). RESULTS: MG patients reached significantly higher scores on the BDI-II and the T-STAI yielding previously undetected anxiety and depression symptoms. Significant differences were present on the SCI: higher stress scores and lower coping levels suggested impaired stress-coping strategies in migraine. MG patients achieved significantly lower scores on most of SF-36 subscales indicating lower perceived quality of life. Significant correlations were found between BDI-II, T-STAI, SCI scores and subscales of the SF-36. CONCLUSION: Unrecognized symptoms of anxiety and depression, as well as less effective stress-coping strategies might be related to the lower perceived quality of life in migraine. The screening of these symptoms might lead to more focused and efficient therapeutic strategies. Addressing stress management techniques could improve quality of life on the long-term.

Kynurenines and PACAP in Migraine: Medicinal Chemistry and Pathogenetic Aspects.

BACKGROUND: Migraine is a highly disabling neurovascular primary headache disorder, with its exact pathomechanism being still unrevealed. The current leading hypotheses are based on the sensitization and activation of the trigeminovascular system. OBJECTIVE: To review the literature with focus on the effects of kynurenines (L-kynurenine and kynurenic acid) and pituitary adenylate cyclase-activating polypeptide on the regulation of the trigeminovascular system. METHOD: A literature search was conducted to identify preclinical and clinical publications (198 references) by using the keywords 'kynurenines', 'pituitary adenylate cyclase-activating polypeptide', and 'migraine' in the database of MEDLINE/PubMed up to 10 September 2016 for topical review. Additional filters used included 'review', 'systematic review', 'original article', and 'English language'. RESULTS: L-kynurenine and kynurenic acid act on the glutamatergic system at the level of the second-order nociceptive neurons in the trigeminal nucleus caudalis. Pituitary adenylate cyclase- activating polypeptide is released from the peripheral nerve endings of the trigeminal pseudounipolar neurons and causes vasodilation and mast cell degranulation, leading to consequent peripheral sensitization of the dural nociceptors. Centrally released pituitary adenylate cyclase-activating polypeptide in the trigeminal nucleus caudalis results in the central sensitization of the second-order neurons. The sensitization process leads to the characteristic features of migraine. CONCLUSION: L-kynurenine, kynurenic acid, and pituitary adenylate cyclase-activating polypeptide may have fundamental roles in the initiation of migraine headache attacks.

Alleviation of pain in painful diabetic neuropathy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available. AREAS COVERED: The origin of PDN is enigmatic, and the evidence-based therapeutic guidelines therefore consist only of antidepressants and antiepileptics as first-line recommended drugs. This article relates to a MEDLINE/PubMed systematic search (2005-2015). EXPERT OPINION: The results of the meta-analysis from the aspect of the efficacy of amitriptyline, duloxetine, venlafaxine, gabapentin and pregabalin are favorable, but the placebo response rate is relatively high in patients with neuropathic pain. For personalization of the medication of PDN patients, the optimum dosing, the genotyping of the metabolizing enzymes and optimum biomarkers are needed. As concerns the future perspectives, specific sodium channel subtype inhibitors acting on peripheral nociceptive neurons or modified T-type voltage-gated calcium channel blockers may be promising targets for pharmaceutical innovations. Another attractive strategy for the treatment is based on the effects of monoclonal antibodies against nerve growth factor, sodium channels, specific receptor and cytokines. Botulinum toxin A, capsaicin patch and spinal cord stimulation therapies are the nearest future therapeutic options for the treatment of PDN patients.