Ghrelin is a novel growth hormone-releasing peptide, originally identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R1a). Ghrelin is involved in the regulation of GH release, but it has recently been suggested that ghrelin may have other actions, including effects on appetite, carbohydrate metabolism, heart, kidney, pancreas, gonads, and cell proliferation. The distribution of ghrelin, its functional receptor (type 1a) and the unspliced, non-functional GHS-R type 1b mRNA expression was investigated in various human tissues using classical and real-time reverse transcription and polymerase chain reaction. GHS-R1a was predominantly expressed in the pituitary and at much lower levels in the thyroid gland, pancreas, spleen, myocardium and adrenal gland. In contrast, ghrelin was found in the stomach, other parts of the gut and, indeed, in all the tissues studied (adrenal gland, atrium, breast, buccal mucosa, esophagus, Fallopian tube, fat tissue, gall bladder, human lymphocytes, ileum, kidney, left colon, liver, lung, lymph node, muscle, muscle, myocardium, ovary, pancreas, pituitary, placenta, prostate, right colon, skin, spleen, testis, thyroid, and vein). GHS-R1b expression was also widespread in all tissues studied. The significance of the widespread tissue distribution of ghrelin remains to be determined. These data suggest that ghrelin might have widespread physiological effects via different, partly unidentified, subtypes of the GHS-R in endocrine and non-endocrine tissues.

IntroductionCerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain.MethodsWe provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III).ResultsOur consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications.DiscussionWhen an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate.

The management of multiple sclerosis is becoming increasingly complex with the emergence of new and more effective disease-modifying therapies (DMT). We propose a new treatment paradigm that individualises treatment based on a choice between two interchangeable therapeutic strategies of maintenance-escalation or induction therapy. We propose treating- to-target of no evident disease activity (NEDA) as defined using clinical and MRI criteria. This algorithm requires active monitoring with a rebaselining MRI, at a point in time after the specific DMT concerned has had sufficient time to work, and at least annual MRI studies to monitor for subclinical relapses. Disease activity on the maintenance-escalation therapy arm of the algorithm indicates a sub-optimal treatment response and should trigger a discussion about switching, or escalating, therapy or the consideration of switching to the induction therapy arm of the algorithm. In comparison, disease activity on an induction therapy arm would be an indication for retreatment or a switch to the maintenance-escalation therapy arm. We envisage the definition of NEDA evolving with time as new technological innovations are adopted into clinical practice, for example the normalisation of whole, or regional, brain atrophy rates and cerebrospinal fluid neurofilament levels.