Cerebral Microdialysis: Going Deep into Brain Biochemistry for a Better Understanding of Pathomechanisms of Acute Brain Injury

AbstractPatients with traumatic brain injury (TBI) have variable outcomes subject to intracranial hypertension, ischemia, hypotension, and various biochemical alterations. Multimodality neurointensive monitoring is standard of care for decision making in all severe TBI cases at present in most neurotrauma units. Neuromonitoring tools, such as cerebral microdialysis, may contribute to understanding the pathomechanisms of acute brain injury, provide an early warning of secondary cerebral deterioration (therapeutic window of opportunity), and help in selecting the patients most suitable to benefit from this very invasive surgical rescue therapy. Cerebral microdialysis can be used as a measure of the effect of decompressive craniectomy on neurochemistry derangement and brain energy crisis jeopardizing the injured brain. Present review discusses the cerebral microdialysis, its usefulness, and role in prognostication of severe TBIs, especially in patients post-decompressive craniectomy. The authors also discuss the current consensus guidelines on usage of cerebral microdialysis in TBI patients

Proteomics for the Investigation of Surface-Exposed Proteins in Probiotics

Probiotics are commensal microorganisms that are present in the intestinal tract and in many fermented foods and positively affect human health, promoting digestion and uptake of dietary nutrients, strengthening intestinal barrier function, modulating immune response, and enhancing antagonism toward pathogens. The proteosurfaceome, i.e., the complex set of proteins present on the bacterial surface, is directly involved as leading actor in the dynamic communication between bacteria and host. In the last decade, the biological relevance of surface-exposed proteins prompted research activities exploiting the potentiality of proteomics to define the complex network of proteins that are involved in the molecular mechanisms at the basis of the adaptation to gastrointestinal environment and the probiotic effects. These studies also took advantages of the recent technological improvements in proteomics, mass spectrometry and bioinformatics that triggered the development of ad hoc designed innovative strategies to characterize the bacterial proteosurfaceome. This mini-review is aimed at describing the key role of proteomics in depicting the cell wall protein architecture and the involvement of surface-exposed proteins in the intimate and dynamic molecular dialogue between probiotics and intestinal epithelial and immune cells

Very early onset of ATTRE89Q amyloidosis in a homozygous patient

Case Presentarion: Hereditary transthyretin amyloidosis is a progressive, fatal disease that generally involves the peripheral nervous system, the autonomic nervous system, and the heart. It is autosomal dominant with different penetrance depending on the mutation and the genetic background. Many other missense mutations of the TTR gene may cause the disease. Being an overall rare disease is very rare to observe the condition of homozygosity. In particular, cases of homozygosity have been described in patients with ATTRV30M and ATTRV122I amyloidosis. In the former, the phenotype does not seem to be aggravated, having an age of onset and disease course that does not appear to differ from those of heterozygotes, while in the latter, the onset appears to be earlier. Conclusion: We report the first case of ATTRE89Q amyloidosis in a patient that was homozygous for the E89Q mutation in the TTR gene. The clinical phenotype resulted in the earlier disease onset reported in this form of amyloidosis, suggesting that the homozygous condition may be prognostically negative

Il trattamento del gozzo immerso. La nostra esperienza

Gli Autori, dopo avere accennato alla storia naturale del gozzo immerso, riferiscono la loro esperienza di tale patologia maturata negli ultimi 5 anni, sottolineando i caratteri della complessa sintoma - tologia osservata nei vari casi, la condotta terapeutica seguìta, i buoni risultati ottenuti. Si soffermano quindi ad elencare le molteplici classificazioni, via via proposte. Illustrano le complesse situazioni sia di ordine emodina - mico che respiratorio di particolare interesse anestesiologico. Discutono, infine, sulla diagnostica e soprattutto sul corretto atteggiamento terapeutico il cui obiettivo è duplice: risolvere la sinto - matologia prodotta dalla massa mediastinica ed escludere la possibi - lità di recidiv

6MWT performance correlates with peripheral neuropathy but not with cardiac involvement in patients with hereditary transthyretin amyloidosis (hATTR)

Abstract Hereditary transthyretin amyloidosis (hATTR) is a life-threatening multisystemic disease with sensory-motor peripheral neuropathy, cardiomyopathy and dysautonomia. Although the six-minute walk test (6MWT) is one of the most popular clinical tests to assess functional exercise capacity in cardiopulmonary and neuromuscular diseases, little is known about 6MWT in evaluating hATTR patients. A prospective single-center pilot study was performed in twenty hATTR patients, comparing 6MWT with widely used outcome measures. After 18 months, fourteen patients were re-evaluated. 6MWT performance was highly related with familial amyloidotic polyneuropathy stage and polyneuropathy disability score, and with CMT examination score, neuropathy impairment score-lower limbs and Kumamoto score. There was no correlation with compound autonomic dysfunction test, modified body mass index and numerous indices of heart dysfunction. After 18 months, familial amyloidotic polyneuropathy stage and polyneuropathy disability score systems were not able to reveal any significant change, whereas all other outcome measures significantly worsened. Among the outcome measures monitoring the neuropathic disturbances, neuropathy impairment score-lower limbs showed the highest responsiveness to change (adjusted effect size: 0.79), followed by CMT examination score (0.67), Kumamoto scale (0.65), 6MWT (0.62). 10MWT showed a very small value (0.21). Compound autonomic dysfunction test had a large value (0.91) whereas modified body mass index a small/moderate value (0.49). 6MWT is a simple and sensitive tool to monitor neuropathic involvement but not cardiac dysfunction in hATTR course

Rare among rare: phenotypes of uncommon CMT genotypes

(1) Background: Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited chronic motor and sensory polyneuropathy. Over 100 CMT causative genes have been identified. Previous reports found PMP22, GJB1, MPZ, and MFN2 as the most frequently involved genes. Other genes, such as BSCL2, MORC2, HINT1, LITAF, GARS, and autosomal dominant GDAP1 are responsible for only a minority of CMT cases. (2) Methods: we present here our records of CMT patients harboring a mutation in one of these rare genes (BSCL2, MORC2, HINT1, LITAF, GARS, autosomal dominant GDAP1). We studied 17 patients from 8 unrelated families. All subjects underwent neurologic evaluation and genetic testing by next-generation sequencing on an Ion Torrent PGM (Thermo Fischer) with a 44-gene custom panel. (3) Results: the following variants were found: BSCL2 c.263A > G p.Asn88Ser (eight subjects), MORC2 c.1503A > T p.Gln501His (one subject), HINT1 c.110G > C p.Arg37Pro (one subject), LITAF c.404C > G p.Pro135Arg (two subjects), GARS c.1660G > A p.Asp554Asn (three subjects), GDAP1 c.374G > A p.Arg125Gln (two subjects). (4) Expanding the spectrum of CMT phenotypes is of high relevance, especially for less common variants that have a higher risk of remaining undiagnosed. The necessity of reaching a genetic definition for most patients is great, potentially making them eligible for future experimentations

Primary progressive aphasia: six questions in search of an answer

Here, we review recent progress in the diagnosis and management of primary progressive aphasia—the language-led dementias. We pose six key unanswered questions that challenge current assumptions and highlight the unresolved difficulties that surround these diseases. How many syndromes of primary progressive aphasia are there—and is syndromic diagnosis even useful? Are these truly ‘language-led’ dementias? How can we diagnose (and track) primary progressive aphasia better? Can brain pathology be predicted in these diseases? What is their core pathophysiology? In addition, how can primary progressive aphasia best be treated? We propose that pathophysiological mechanisms linking proteinopathies to phenotypes may help resolve the clinical complexity of primary progressive aphasia, and may suggest novel diagnostic tools and markers and guide the deployment of effective therapies

Quantitative comparison between amyloid deposition detected by (99m)Tc-Diphosphonate imaging and myocardial deformation evaluated by strain echocardiography in transthyretin-related cardiac amyloidosis.

Methods and results 28 patients with transthyretin mutation and a group of 14 controls underwent echocardiography to quantify left ventricular (LV) dimensions and function, and global (G) longitudinal (L), radial (R) and circumferential (C) strain (S). 99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic-acid-scintigraphy (99mTc-DPD) was used to quantify cardiac amyloidosis (CA). 99mTc-DPD revealed accumulation in 14 of 28 patients (CA-group) and no accumulation (no CA-group) in 14 patients. Cardiac accumulation was mild-moderate in 5 (Mild-Moderate CA-group) and severe in 9 patients (Severe CA-group). Severe CA-group showed higher values of LV septal thickness (LVST), posterior wall thickness and E/E' ratio than the no CA-group and the control group (adj. p<0.05). Ejection fraction was similar among groups (p=0.65). GLS was lower (p=<0.001) in severe CA-group (-12.2 ± 4.5) respect to no CA-group (-19.3 ± 3.0) and to the control group (-20.9 ± 2.5). On the contrary, GCS and GRS were lower (p=<0.05) in mild-moderate CA-group (-10.8 ± 4.1 and 9.5 ± 5.7, respectively) respect to the severe CA-group (-18.9 ± 5.1 and 23.9 ± 6.3 respectively), no CA-group (-19.2 ± 4.1 and 28.4 ± 10.2 respectively) and the control group (-23.9 ± 4.4 and 29.9 ± 8.7 respectively). A correlation was found between the scintigraphic heart retention (HR) index and LVST (r=0.72; p<0.001) and E/E' (r=0.46; p=0.03). An inverse tendency was observed between HR and GLS (r=−0.40; p=0.06)