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Background: In recent years, due to the epidemiological transition, the burden of very complex patients in hospital wards has increased. Telemedicine usage appears to be a potential high-impact factor in helping with patient management, allowing hospital personnel to assess conditions in out-of-hospital scenarios. Methods: To investigate the management of chronic patients during both hospitalization for disease and discharge, randomized studies (LIMS and Greenline-HT) are ongoing in the Internal Medicine Unit at ASL Roma 6 Castelli Hospital. The study endpoints are clinical outcomes (from a patient’s perspective). In this perspective paper, the main findings of these studies, from the operators’ point of view, are reported. Operator opinions were collected from structured and unstructured surveys conducted among the staff involved, and their main themes are reported in a narrative manner. Results: Telemonitoring appears to be linked to a reduction in side-events and side-effects, which represent some of most commons risk factors for re-hospitalization and for delayed discharge during hospitalization. The main perceived advantages are increased patient safety and the quick response in case of emergency. The main disadvantages are believed to be related to low patient compliance and an infrastructural lack of optimization. Conclusions: The evidence of wireless monitoring studies, combined with the analysis of activity data, suggests the need for a model of patient management that envisages an increase in the territory of structures capable of offering patients subacute care (the possibility of antibiotic treatments, blood transfusions, infusion support, and pain therapy) for the timely management of chronic patients in the terminal phase, for which treatment in acute wards must be guaranteed only for a limited time for the management of the acute phase of their diseases.

Ramsay Hunt syndrome is due to reactivation of varicella zoster virus (VZV) dormant in the geniculate ganglion of the facial nerve. The diagnosis is typically based on clinical triad of ipsilateral facial paralysis, otalgia, and vesicles in the auditory canal or the auricle. However, Ramsay Hunt syndrome may occur without skin eruption in up to one third of patients. Moreover, the involvement of other cranial nerves in addition to the facial nerve has been also reported. Herein, we reported a case report of a man who developed a multiple cranial neuropathy caused by VZV reactivation without skin vesicular eruption. The present case underlines a possible diagnostic challenge that clinicians may hit when facing a common disorder such as peripheral facial palsy. Indeed, clinicians must be aware that Ramsay Hunt syndrome may develop without skin vesicular eruption as well it may be complicated by multiple cranial nerve involvement. Antiviral therapy is effective in VZV reactivation for recovery of nerve function.

Botulinum toxin (BT) is an effective treatment for spasticity symptoms in multiple sclerosis (MS). Despite its wide use in clinical practices, only few studies have explored long-term persistence. We aim to evaluate the rate of discontinuation of BT treatment and the correlation with MS, spasticity, and injection variables. This retrospective study on 3-year prospectively collected data included 122 MS patients receiving BT injections for spasticity. We collected MS clinical variables (disease durations, Expanded Disability Status Scales [EDSSs], disease-modifying treatments [DMT], and Symbol Digit Modalities Tests [SDMTs]), modified Ashworth scales [MASs], concomitant treatments, and injection variables (formulation, dose, number of injections, and intervals between injections). A total of 14 out of the 122 patients discontinued BT after a mean time of 3.0 ± 1.5 years. In the Cox regression model including the MS clinical variables, the probability of BT discontinuations increased in patients with DMT changes during follow-ups (HR = 6.34; 95%Cl = 2.47, 18.08; p < 0.01) and with impaired SDMTs (HR = 1.20; 95%Cl = 1.04, 1.96; p < 0.01). In the model including the spasticity variables, there were no associations between BT discontinuation and MAS or other spasticity treatments. In the model including the injection variables, the probability of discontinuation decreased by 80% for each cumulative injection (HR = 0.16; 95%Cl = 0.05, 0.45; p < 0.01), but increased by 1% for each additional day over the 3-month interval between injections (HR = 1.27; 95%Cl = 1.07, 1.83; p < 0.01). BT discontinuation was associated with concomitant MS-related issues (e.g., treatment failure and DMT change) and the presence of cognitive impairment, which should be accounted for when planning injections. The interval between injections should be kept as short as possible from regulatory and clinical perspectives to maximize the response across all of the spasticity symptoms and to reduce discontinuation in the long term.

Backgrounds Hereditary transthyretin amyloidosis (ATTRv) presymptomatic subjects undergo multidisciplinary evaluation to detect, as early as possible, a subclinical involvement of multisystem disease. Quantitative sensory testing (QST) that investigates and discriminates the function of C, Aδ and Aβ fibers is included as an instrumental test to monitor nerve fiber function. The purpose of this study was to evaluate the role of QST in the context of the multidisciplinary evaluation in late onset carriers. Methods Four-teen presymptomatic (namely carriers) were enrolled. Subjects underwent thermal [cold and warm detection threshold (CDT, WDT), cold and heat pain (CP and HP)] and tactile QST in four body sites: foot dorsum, distal lateral leg, distal thigh, hand dorsum. Results Overall, presymptomatic subject showed a significant difference in all thermal QST findings compared to the control group. All subjects had at least one altered thermal QST finding; the sites more frequently altered were foot and leg, whilst the thermal modalities which were more frequently abnormal were CDT, WDT and CP. Conclusions Our study highlights the importance of performing thermal QST in subjects carrying TTR mutation, given the high frequency of abnormal findings. Notably, performing both innocuous and painful stimulation in foot and/or leg increases the chance of detecting nerve fiber dysfunction. Moreover, the investigation of the hand may provide useful information in monitoring disease progression before the Predicted Age of Disease Onset (PADO).

Treatment-resistant schizophrenia (TRS) affects approximately one-third of individuals with schizophrenia, posing significant challenges for clinical management. Clozapine treatment is often delayed, underscoring the urgent need for an early potential signature of TRS. To date, specific alterations in cortical excitability and plasticity underlying TRS remain unexplored. We evaluated cortical excitability and plasticity in 30 patients with schizophrenia (15 TRS, 15 non-TRS) and 21 controls using transcranial magnetic stimulation (TMS). Measures included motor thresholds and protocols probing GABAergic inhibition and glutamatergic facilitatory activity, the excitation index (EI) in the primary motor cortex (M1), and long-term potentiation (LTP)-like plasticity using intermittent theta burst stimulation (iTBS). Clinical severity and cognitive performance were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS). TRS patients exhibited significantly higher active motor thresholds (p = 0.015) and impaired short-interval intracortical inhibition (SICI) (p = 0.001) vs healthy controls, reflecting GABAergic dysfunction. EI was elevated in TRS vs non-TRS patients (p = 0.034) and controls (p = 0.002), indicating pronounced cortical hyperexcitability. Both TRS (p = 0.008) and non-TRS patients (p = 0.033) showed reduced plasticity following iTBS compared to controls, with no TRS vs non-TRS difference. SICI deficits significantly correlated with negative (r = 0.524, padj = 0.03) and autistic (r = 0.517, padj = 0.03) symptom severity as assessed by the PANSS negative score and Positive and Negative Syndrome Scale Autism Severity Score (PAUSS). Our findings point to a neurophysiological continuum in schizophrenia, with TRS patients demonstrating the most pronounced cortical hyperexcitability and impaired plasticity, and non-TRS patients showing intermediate deficits.

Introduction. Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is an autosomal recessive metabolic disorder resulting from mutations in the genes that encode the electron transfer flavoprotein (ETF) or its associated dehydrogenase (ETFDH), resulting in defects in mitochondrial fatty acid oxidation and a broad range of clinical presentations, most notably in the form of muscle weakness; exercise intolerance; and, in some cases, life-threatening metabolic crises. Late-onset MADD represents the most common form of lipid storage myopathy, but its diagnosis can be elusive due to its varied and often nonspecific clinical symptoms and may resemble other neuromuscular conditions, like inflammatory myopathies or other peripheral neuropathies, complicating the diagnostic process and delaying appropriate treatment. Aims. This case series aims to provide additional insights into the clinical presentation of MADD, highlighting diagnostic challenges in differentiating metabolic myopathies and emphasizing the role of muscle biopsy in diagnosing these conditions. Results. We describe five clinical cases of patients who were diagnosed with MADD, their clinical manifestations, and the diagnostic processes undertaken to arrive at this diagnosis. Notably, three patients were initially misdiagnosed with inflammatory myopathy, and one was misdiagnosed with Guillain–Barré syndrome. The correct diagnosis was established following a muscle biopsy, which revealed characteristic findings consistent with lipid storage myopathy and prompted subsequent biochemical analyses and genetic testing that confirmed the diagnosis of MADD. Conclusions. MADD is an underdiagnosed condition, and the description of new patients with various clinical presentations could support the development of clinical tools to promptly recognize this disease and allow physicians to deliver the most appropriate and effective therapy protocol, with Riboflavin and Carnitine supplementations, avoiding inappropriate treatments. The muscle biopsy was essential for a correct diagnostic assessment.

Abnormalities in retinal vascularization and neural density have been found in many neurodegenerative diseases; however, conflicting results are described in Amyotrophic Lateral Sclerosis (ALS). The aim of the present study was, therefore, to systematically analyze retinal layers and vascularization by means of spectral-domain (SD-OCT) and optical coherence tomography angiography (OCT-A) in ALS patients. We enrolled 48 ALS patients and 45 healthy controls. ALS patients were divided into three groups: slow progressors (n = 10), intermediate progressors (n = 24) and fast progressors (n = 14), according to the disease progression rate. For SD-OCT, we evaluated the Subfoveal choroidal thickness (SFCT), ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Regarding the OCT-A, we assessed the vessel density (VD) in superficial and deep capillary plexuses, radial peripapillary capillary plexus, choriocapillary and the foveal avascular zone (FAZ) area. SD-OCT exam did not show any significant differences in GCC and RNFL thickness between patients and controls and among the three ALS groups. The SFCT was statistically greater in patients compared with controls (357.95 ± 55.15 µm vs. 301.3 ± 55.80 µm, p < 0.001); interestingly, the SFCT was thicker in patients with slow and intermediate disease progression than in those with fast disease progression (394.45 ± 53.73 µm vs. 393.09 ± 42.17 µm vs. 267.71 ± 56.24 µm, p < 0.001). OCT-A did not reveal any significant results. Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r) and disease duration did not correlate with any of the OCT parameters, except for SFCT with ALSFRS-r (r = 0.753, p = 0.024). This study demonstrated the possible association between choroidal thickness and disease activity in ALS. OCT could be a useful biomarker in the management of the disease.

Background and aimNeurodegeneration with brain iron accumulation (NBIA) and Wilson’s disease (WD) is considered the prototype of neurodegenerative disorders characterised by the overloading of iron and copper in the central nervous system. Growing evidence has unveiled the involvement of these metals in brain cortical neurotransmission. Aim of this study was to assess cortical excitability profile due to copper and iron overload.MethodsThree patients affected by NBIA, namely two patients with a recessive hereditary parkinsonism (PARK9) and one patient with aceruloplasminemia and 7 patients with neurological WD underwent transcranial magnetic stimulation (TMS) protocols to assess cortical excitability. Specifically, we evaluated the motor thresholds that reflect membrane excitability related to the voltage-gated sodium channels in the neurons of the motor system and the ease of activation of motor cortex via glutamatergic networks, and ad hoc TMS protocols to probe inhibitory-GABAergic (short interval intracortical inhibition, SICI; short-latency afferent inhibition, SAI; cortical silent period, CSP) and excitatory intracortical circuitry (intracortical facilitation, ICF).ResultsPatients with NBIA exhibited an abnormal prolongation of CSP respect to HC and WD patients. On the contrary, neurological WD displayed higher motor thresholds and reduced CSP and SICI.ConclusionHereditary conditions due to overload of copper and iron exhibited peculiar cortical excitability profiles that can help during differential diagnosis between these conditions. Moreover, such results can give us more clues about the role of metals in acquired neurodegenerative disorders, such as Parkinson disease, Alzheimer disease, and multiple sclerosis.

Chronic dysimmune neuropathies encompass a group of neuropathies that share immune-mediated pathomechanism. Chronic dysimmune antibody-related neuropathies include anti-MAG neuropathy, multifocal motor neuropathy, and neuropathies related to immune attack against paranodal antigens. Such neuropathies exhibit distinguishing pathomechanism, clinical and response to therapy features with respect to chronic inflammatory demyelinating polyradiculoneuropathy and its variants, which represent the most frequent form of chronic dysimmune neuropathy. This narrative review provides an overview of pathomechanism; clinical, electrophysiological, and biochemical features; and treatment response of the antibody-mediated neuropathies, aiming to establish when and why to look for antibodies in chronic dysimmune neuropathies.

Reactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of peroxides. We found that antigen-dependent activation represents a triggering element for SOD-1 production and secretion by human T lymphocytes. A deranged T-cell proinflammatory response characterizes the pathogenesis of multiple sclerosis (MS). We previously observed a decreased SOD-1 intracellular content in leukocytes of MS individuals at diagnosis, with increasing amounts of such enzyme after interferon (IFN)-b 1b treatment. Here, we analyzed in depth SOD-1 intracellular content in T cells in a cohort of MS individuals undergoing immune-modulating treatment. Higher amounts of the enzyme were associated with increased availability of regulatory T cells (Treg) preferentially expressing Foxp3-exon 2 (Foxp3-E2), as described for effective Treg. In vitro administration of recombinant human SOD-1 to activated T cells, significantly increased their IL-17 production, while SOD-1 molecules lacking dismutase activity were unable to interfere with cytokine production by activated T cells in vitro. Furthermore, hydrogen peroxide addition was observed to mimic, in vitro, the SOD-1 effect on IL-17 production. These data add SOD-1 to the molecules involved in the molecular pathways contributing to re-shaping the T-cell cytokine profile and Treg differentiation.