Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

Magnetic resonance imaging differential diagnosis of brainstem lesions in children

Differential diagnosis of brainstem lesions,either isolated or in association with cerebellar and supra-tentorial lesions,can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential,especially in the pediatric population. Magnetic resonance imaging(MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and,particularly,the brainstem. High magnetic static field MRI allows detailed visualization of the morphology,signal intensity and metabolic content of the brainstem nuclei,together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular,toxico-metabolic,infectiveinflammatory,degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions,the brainstem vascularization territories,gray and white matter distribution and tissue selective vulnerability.

Enteroscopy in children and adults with inflammatory bowel disease

Inflammatory bowel disease(IBD)includes Crohn’s disease(CD),ulcerative colitis and unclassified entities.CD commonly involves the terminal ileum and colon but at the time of diagnosis it can be confined to the small bowel(SB)in about 30%of the patients,especially in the young ones.Management of isolated SB-CD can be challenging and objective evaluation of the SB mucosa is essential in differentiating CD from other enteropathies to achieve therapeutic decisions and to plan the follow-up.The introduction of cross-sectional imaging techniques and capsule endoscopy(CE)have significantly expanded the ability to diagnose SB diseases providing a non-invasive test for the visualization of the entire SB mucosa.The main CE limitations are the low specificity,the lack of therapeutic capabilities and the impossibility to take biopsies.Device assisted enteroscopy(DAE)enables histological confirmation when traditional endoscopy,capsule endoscopy and cross-sectional imaging are inconclusive and also allows therapeutic interventions such as balloon stricture dilation,intralesional steroid injection,capsule retrieval and more recently stent insertion.In the current review we will discuss technical aspect,indications and safety profile of DAE in children and adults with IBD.

Levodopa/Carbidopa Intestinal Gel for Treatment of Advanced Parkinson’s Disease: An Update on the Effects of Cognitive Functions

Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circuitries. In advanced stages, worsening of dysexecutive symptoms is accompanied by disorientation and memory deficit leading to dementia in 30% of cases, due to multiple neurotransmitter derangement. Dysexecutive symptoms in the early stages of PD may benefit from dopamine replacement therapy (DRT). Conversely, severe cognitive symptoms in more advanced stages are frequently aggravated by DRT. In particular, pulsatile stimulation of dopaminergic receptors by orally administered levodopa (LD) plays a significant negative role on cognitive and neuropsychiatric symptoms in advanced PD. The introduction of a gel of LD-carbidopa for continuous intestinal administration (LCIG) allows marked stabilization of plasma LD concentrations and provides benefit on motor fluctuations and dyskinesia of significantly greater magnitude than conventional oral administration in advanced PD patients. The results from several preliminary studies suggest that efficacy of LCGI on motor symptoms may be accompanied by good tolerability and potential benefit on several non-motor symptoms, including cognitive impairment. Future studies with longer observation period and larger cohorts are advised to confirm these preliminary observations.

Early onset versus late onset in Alzheimer’s disease: What is the reliable cut-off?

Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer’s disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two sub-groups. Methods: Admixture analysis was performed to establish the AAO cut-off in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychoticor anti-depressant drugs. At the first diagnosticvisit, they were administered the Mini Mental StateExamination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventorytoassess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EO-from LO-AD was 66. Compared with the LO-AD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two sub-groups of AD patients.

COVID-19 pandemic:An update on the reaction attitude of the spine societies and their members worldwide

BACKGROUND All surgical specialties have been influenced by the coronavirus disease 2019(COVID-19)pandemic,and substantial changes have been determined in medical assistance,especially in elective surgery.Several spine societies have published recommendations to provide optimal care during this unique situation.AIM To discuss the recommendations by many spine societies for the management of spinal diseases during the COVID-19 pandemic.METHODS The present study was performed according to the PRISMA guidelines.A review of the MEDLINE database(PubMed–National Library of Medicine),Google,and Google Scholar was performed from March 2020 to date for articles published in the English Language.RESULTS Spine associations and societies worldwide were divided into three groups:Continental,specialty and country-based societies.A total of 27 spine associations were included in this review.There were eight major continental associations,but only one-third of these had published guidelines and recommendations on this topic.On the other hand,the specialty-based societies have not addressed the topic,except in two cases.CONCLUSION The national spine societies showed the deepest concern on this topic with several publications in scientific journals influenced by the local epidemiological severity.Contrarily,continental and specialty-based societies showed less interest in this topic.

Memantine: New prospective in bipolar disorder treatment

We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manicdepressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity(mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon(dopamine receptor desensitization) and an increased immobility time(depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action(at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in maniclike symptoms occurring in psychiatric disorders other than bipolar. Limitations: A randomized controlled clinical trial is needed to confirm our naturalistic observations.Conclusion: We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.

Respiratory syncytial virus and adenovirus in acute lower respiratory infections in hospitalized infants and children

Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than human adenovirus (HAdV) in cold seasons;recent data suggest that oropharyngeal swabs more frequently contain HAdV than RSV. Knowing more about virus detection with oropharyngeal swabs, seasonal fluctuations and age-related distribution of RSV and HAdV would help treat children hospitalized for LRTI more effectively. We investigated the seasonal virus-related frequency (as assessed by oropharyngeal swabs) and environmental and clinical features in infants and children hospitalized for LRTI from autumn to spring. Methods: We studied 98 subjects hospitalized for LRTI in our Pediatric Unit, from November 2006 to May 2007. RSV and HAdV in oropharyngeal swabs were assessed by real-time polymerase chain reaction (PCR) assay. Results: PCR assays more frequently detected HAdV (29.6% of patients) than RSV (25.5%). The seasonal incidence also differed (RSV, narrow peak in December and HAdV, wide peak from April to May). Most patients infected with RSV were aged 2 yrs or younger (23/25: 88%);no difference was found in age between subjects who tested HAdV-positive (13/29: 45%) or undetectable-virus (23/44: 52%). Bronchiolitis was more frequently associated with RSV than HAdV or undetectable-virus oropharyngeal swabs. No difference was found in risk factors (school attendance, atopic parents, exposure to cigarette smoking, home dampness or exposure to animals) or clinical features (vital parameters or duration of hospital stay) among the three viral groups. Conclusions: Our findings show a high frequency of HAdV-positive oropharyngeal swabs during acute LRTIs in infants and children and differences in the seasonal distribution of RSV and HAdV in Rome.

Role of stem cells-based in facial nerve reanimation:A meta-analysis of histological and neurophysiological outcomes

BACKGROUND Treatments involving stem cell(SC)usage represent novel and potentially interesting alternatives in facial nerve reanimation.Current literature includes the use of SC in animal model studies to promote graft survival by enhancing nerve fiber growth,spreading,myelinization,in addition to limiting fibrotic degeneration after surgery.However,the effectiveness of the clinical use of SC in facial nerve reanimation has not been clarified yet.AIM To investigate the histological,neurophysiological,and functional outcomes in facial reanimation using SC,compared to autograft.METHODS Our study is a systematic review of the literature,consistently conducted according to the preferred reporting items for systematic reviews and meta-analyses statement guidelines.The review question was:In facial nerve reanimation on rats,has the use of stem cells revealed as effective when compared to autograft,in terms of histological,neurophysiological,and functional outcomes?Random-effect meta-analysis was conducted on histological and neurophysiological data from the included comparative studies.RESULTS After screening 148 manuscript,five papers were included in our study.43 subjects were included in the SC group,while 40 in the autograft group.The meta-analysis showed no significative differences between the two groups in terms of myelin thickness[CI:-0.10(-0.20,0.00);I^(2)=29%;P=0.06],nerve fibers diameter[CI:0.72(-0.93,3.36);I^(2)=72%;P=0.6],compound muscle action potential amplitude[CI:1.59(0.59,3.77);I^(2)=89%;P=0.15]and latency[CI:0.66(-1.01,2.32);I^(2)=67%;P=0.44].The mean axonal diameter was higher in the autograft group[CI:0.94(0.60,1.27);I^(2)=0%;P≤0.001].CONCLUSION The role of stem cells in facial reanimation is still relatively poorly studied,in animal models,and available results should not discourage their use in future studies on human subjects.

Granulomatous Inflammatory Reaction in Breast Silicone Implants

Introduction： breast implants have been used to correct the size and the form of a breast in post-mastectomy breast reconstruction, for correcting congenital defects and deformities or for purely aesthetic breast augmentation. Silicone breast implants were introduced in the 1960s. They are non without complications, like rupture is or silicone gel bleeding. Materials and methods： the authors present the case of 50 patients, aged 45-55, who presented to our attention after 15 （＋ 5） years of the application of silicone breast implant for the appearance of lumps under the skin in the armpit area. These were palpable, painless except on palpation. The patients reported burning in the affected area, but no other symptoms. Results： considering the presence in each of them of silicone implants, and assuming a possible allergic basis, the authors performed a patch test series S1DAPA produced by F.I.R.M.A Spa, Firenze, ultrasound and MR and blood tests. In all patients the allergy test （patch test） were negative, ultrasound and MR have shown that no hearing was damaged or broken. Blood test showed no abnormalities. Discussion： comparing the authors＇ study with other similar works in the literature, they noted that the reported cases of hypersensitivity type 4 silicone prosthesis was not only initially accompanied by specific symptoms such as urticaria and blistering, but mostly it was found to be a net positive patch test. The absence of urticaria, the low values of lgE and total negativity of patch test confirmed the purely inflammatory nature of the lesions in our patients.

COVID-19 pandemic in the intensive care unit:Psychological implications and interventions,a systematic review

BACKGROUND The coronavirus disease 2019(COVID-19) pandemic produced changes in intensive care units(ICUs) in patient care and health organizations. The pandemic event increased patients’ risk of developing psychological symptoms during and after hospitalisation. These consequences also affected those family members who could not access the hospital. In addition, the initial lack of knowledge about the virus and its management, the climate of fear and uncertainty, the increased workload and the risk of becoming infected and being contagious, had a strong impact on healthcare staff and organizations. This highlighted the importance of interventions aimed at providing psychological support to ICUs, involving patients, their relatives, and the staff;this might involve the reorganisation of the daily routine and rearrangement of ICU staff duties.AIM To conduct a systematic review of psychological issues in ICUs during the COVID-19 pandemic involving patients, their relatives, and ICU staff.METHODS We investigated the PubMed and the ClinicalTrials.gov databases and found 65 eligible articles,upon which we commented.RESULTS Our results point to increased perceived stress and psychological distress in staff, patients and their relatives and increased worry for being infected with severe acute respiratory syndrome coronavirus-2 in patients and relatives. Furthermore, promising results were obtained for some psychological programmes aiming at improving psychological measures in all ICU categories.CONCLUSION As the pandemic limited direct inter-individual interactions, the role of interventions using digital tools and virtual reality is becoming increasingly important. All considered, our results indicate an essential role for psychologists in ICUs.