Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.     

The clinical significance of keratinized gingiva around dental implants

Whether or not keratinized tissue is needed around dental implants to maintain peri-implant health is a controversial subject. To clarify this issue a search was conducted for clinical trials that appraised the significance ofkeratinized gingiva (KG) around teeth and dental implants. A critical assessment of the data revealed that the literature is replete with studies that contradict one another with respect to the need for KG as it relates to survivability of implants, gingival response to plaque, inflammation, probing depths, recession, and loss of bone. When groups of patients with and without KG were compared with respect to various clinical parameters, a statistically significant better result in the presence of KG could be interpreted to indicate that having KG is advantageous. However, quantitative differences between groups with and without KG were usually very small. Overall, the data was interpreted to indicate that some patients may need augmentation of keratinized tissue to maintain peri-implant health. Ultimately, the decision to augment KG is a judgment call that needs to be made by the treating clinician, because there are not enough data to facilitate development of definitive guidelines relevant to this subject. Apparently, the need for KG is patient specific, and at present there is no method to reliably predict who would benefit from tissue augmentation.     

The relationship between biologic concepts and fabrication of surgical guides for dental implant placement

This article reviews guidelines for construction of surgical guides to direct dental implant placement. Biologic principles are discussed with regard to the mesiodistal, buccolingual, and apicocoronal insertion of implants. The application of these data to develop surgical guides is discussed. Also, with respect to specific prosthetic reconstructions, a variety of guides are described that can be fabricated for partially and fully edentulous arches.     

Clinical recommendations for avoiding and managing surgical complications associated with implant dentistry: a review

Proposing to place endosseous implants is an integral facet of dental treatment plans. Their insertion is usually associated with a low incidence of untoward events. However, despite careful planning, surgical complications can arise: infection, intraoral hemorrhage, wound dehiscence, postoperative pain, lack of primary implant stability, inadvertent penetration into the maxillary sinus or nasal fossa, sinus lift sequelae, neurosensory disturbances, injuries to adjacent teeth, tissue emphysema, and aspiration, or ingestion of surgical instruments. This article addresses some surgical complications associated with dental implant placement and discusses how to avoid and manage them when they occur.     

Influence of antisecretory treatment with proton pump inhibitors on serum pepsinogen I levels

It has been reported in literature that serum pepsinogen levels rise during omeprazole and lansoprazole administration. However, the influence of pantoprazole and esomeprazole on serum pepsinogens levels is still to be assessed. The aim of this study was to evaluate the influence of proton pump inhibitor (PPI) therapy on pepsinogen I (PGI) levels. PGI and gastrin (G17) levels (EIA; Biohit, Helsinki, Finland) in 126 consecutive patients (M 57; F 69, mean age 53, range 15-91), with upper gastrointestinal symptoms at baseline condition and after 2 months of PPI treatment, were evaluated. Patients underwent a therapy schedule based on: omeprazole 20 mg b.i.d. (20 patients), pantoprazole 40 mg b.i.d. (27 patients), esomeprazole 40 mg b.i.d. (29 patients), lansoprazole 30 mg b.i.d. (21 patients) and rabeprazole 20 mg b.i.d. (26 patients) for 2 months. A significant increase in serum PGI (sPGI) levels was found after a 2-month treatment for all five different PPIs: omeprazole, pantoprazole, esomeprazole, lansoprazole and rabeprazole (P < 0.05). The effect of rabeprazole on sPGI was less pronounced as compared with other PPIs, whereas esomeprazole achieved superior sPGI levels, with no overall statistically significant difference among the five groups (P > 0.05). However, a comparison within a single group of PPIs showed a statistical significance when the esomeprazole group was compared with the rabeprazole group (P = 0.007). sPGI levels are significantly influenced by antisecretory therapy, rising under PPI treatment. Moreover, a statistically significant difference in sPGI levels between the rabeprazole and esomeprazole groups has been demonstrated.     

Hypnotizability and Sensorimotor Integration: An Italian Space Agency Project

In highly hypnotizable individuals (highs), postural control is more independent of sensory information than in low hypnotizable subjects (lows). The aim of the study was to find out whether locomotion is also less affected in highs than in lows by visual suppression and changes in the neck proprioceptive input. Eighteen highs and 20 lows were asked to walk straight ahead, blindfolded, in basal conditions (face forward), during real and imagined right/left head rotation and mental computation. Highs detected deviations from the straight trajectory better than lows. Their walking direction was more straight during basal conditions and less influenced than the lows' one by mental computation and real/imagined rotation of the head. The results confirm highs' lower dependence on sensory inputs, although this cannot be definitely attributed to a better internal representation of space or to higher behavioral automaticity.     

Core-Shell Arginine-Containing Chitosan Microparticles for Enhanced Transcorneal Permeation of Drugs

Chitosan oligosaccharide (C) was functionalized with l-arginine (A) and short hydrocarbon chains (C₈) to design an amphiphilic copolymer, henceforth CAC₈, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). l-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC₈ MPs (CAC₈-MPs) were studied, showing that CAC₈-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC₈-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity.     

Endothelin-1 Induces Degeneration of Cultured Motor Neurons Through a Mechanism Mediated by Nitric Oxide and PI3K/Akt Pathway

Endothelin-1 (ET-1) is a vasoactive peptide produced by activated astrocytes and microglia and is implicated in initiating and sustaining reactive gliosis in neurodegenerative diseases. We have previously suggested that ET-1 can play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Indeed, we reported that this peptide is abundantly expressed in reactive astrocytes in the spinal cord of SOD1-G93A mice and ALS patients and exerts a toxic effect on motor neurons (MNs) in an in vitro model of mixed spinal cord cultures enriched with reactive astrocytes. Here, we explored the possible mechanisms underlying the toxic effect of ET-1 on cultured MNs. We show that ET-1 toxicity is not directly caused by oxidative stress or activation of cyclooxygenase-2 but requires the synthesis of nitric oxide and is mediated by a reduced activation of the phosphoinositide 3-kinase pathway. Furthermore, we observed that ET-1 is also toxic for microglia, although its effect on MNs is independent of the presence of this type of glial cells. Our study confirms that ET-1 may contribute to MN death and corroborates the view that the modulation of ET-1 signaling might be a therapeutic strategy to slow down MN degeneration in ALS.     

Brain and cancer: the protective role of erythropoietin

Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia-induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neurotransmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issue, because of its possible action as a growth and an angiogenic factor. In our speculative hypothesis Epo could be involved in a "two steps process" that, after a neovascularization phase, leads to its down regulation. Moreover, Epo-activated signaling pathways could be modulated as possible targets to interfere in neoplastic cells cycle. In conclusion, treatment with rHuEpo could change therapeutical perspectives in different pathological conditions, such as central nervous system (CNS) diseases, but further studies are needed to clarify its physiopathological activities in different clinical fields.     

The Italian Registry of Therapeutic Apheresis: granulocyte-monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte-monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn's disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn's disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered.