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Chemotherapy-induced neuropathy (CIN) is a major adverse effect associated with many chemotherapeutics, including bortezomib (BTZ). Several mechanisms are involved in CIN, and recently a role has been proposed for prokineticins (PKs), a chemokine family that induces proinflammatory/pro-algogen mediator release and drives the epigenetic control of genes involved in cellular differentiation. The present study evaluated the relationships between epigenetic mechanisms and PKs in a mice model of BTZ-induced painful neuropathy. To this end, spinal cord alterations of histone demethylase KDM6A, nuclear receptors PPARα/PPARγ, PK2, and pro-inflammatory cytokines IL-6 and IL-1β were assessed in neuropathic mice treated with the PK receptors (PKRs) antagonist PC1. BTZ treatment promoted a precocious upregulation of KDM6A, PPARs, and IL-6, and a delayed increase of PK2 and IL-1β. PC1 counteracted allodynia and prevented the increase of PK2 and of IL-1β in BTZ neuropathic mice. The blockade of PKRs signaling also opposed to KDM6A increase and induced an upregulation of PPAR gene transcription. These data showed the involvement of epigenetic modulatory enzymes in spinal tissue phenomena associated with BTZ painful neuropathy and underline a role of PKs in sustaining the increase of proinflammatory cytokines and in exerting an inhibitory control on the expression of PPARs through the regulation of KDM6A gene expression in the spinal cord.

Changes of brain structure and function have been described in peripheral neuropathies. The aim of our study was to systematically investigate possible modifications of major large-scale brain networks using resting-state functional magnetic resonance imaging (RS-fMRI) in Charcot–Marie–Tooth disease type 1A (CMT1A) patients. In this cross-sectional study, 3-T MRI brain scans were acquired of right-handed genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing neurological impairment. RS-fMRI data were analysed using a seed-based approach, with 32 different seeds sampling the main hubs of default mode, sensorimotor, visual, salience (SN), dorsal attention, frontoparietal, language and cerebellar networks. Between-group differences in terms of functional connectivity (FC) with the explored seeds were tested voxelwise, correcting for local grey matter density to account for possible structural abnormalities, whilst the relationship between FC modifications and neurological impairment was investigated using robust correlation analyses. Eighteen CMT1A patients (34.0  11.4 years; M/F 11/7) were enrolled, along with 20 healthy controls (30.1  10.2 years; M/F 11/9). In the CMT group compared to controls, clusters of increased FC with the visual cortex (P = 0.001), SN (P < 6 9 10 4), dorsal attention network (P < 8 9 105) and language network (P < 7 9 10–4) were found, along with a single cluster of reduced FC with the visual cortex in the left lentiform nucleus (P = 10–6). A significant correlation emerged between neurophysiological impairment and increased FC with right temporal language areas (r = 0.655, P = 0.006), along with an association between walking ability and increased FC with the left supramarginal gyrus (SN) (r = 0.620, P = 0.006). Our data show evidence of diffuse functional reorganization involving multiple large-scale networks in the CMT1A brain, independent of structural modifications and partially correlating with peripheral nerve damage and functional impairment.

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Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (

Central nervous system involvement has been described in peripheral neuropathies, including different forms of Charcot-Marie-Tooth (CMT) disease. The aimof our study was to systematically investigate possible brain structural modifications in CMT1A patients, using volumetric MRI, and diffusion tensor imaging (DTI). In this prospective cross-sectional study, from May 2017 to May 2019, we acquired 3T MRI brain scans of genetically confirmed CMT1A patients and age- and sex-comparable healthy controls. Patients also underwent clinical and electrophysiological examinations assessing motor and sensory domains. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were performed using a non-parametric approach based on permutations, including age and sex (and total intracranial volume for VBM) as nuisance covariates. When between-group differences emerged at VBM or TBSS analyses, the first eigenvariate was extracted from the cluster and its age- and sex-adjusted standardized residuals tested for correlation with clinical and electrophysiological variables. Twenty CMT1A patients (34.5 +/- 11.1 years; M/F:11/9) were enrolled, along with 20 healthy controls (30.1 +/- 10.2 years; M/F:11/9). The VBM analysis revealed clusters of significantly increased GM volume in CMT1A patients compared to healthy controls, encompassing the bilateral cerebellar lobules III-VI and the left hippocampus (all ps = 0.04), with no differences in terms of DTI metrics at the TBSS analysis. A negative correlation (r = -0.502, p = 0.03) emerged between ulnar compound motor action potential and the z-scores corresponding to the right cerebellar cluster of augmented GM volume. Our data show evidence of structural reorganization in the brain of CMT1A patients, possibly reflecting neural plasticity mechanisms in response to peripheral nerve pathology and modulating the effect of axonal degeneration on functional impairment.

Background Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients’ health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients’ reported health instruments for use in routine clinical practice. Methods At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. Results Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p

Background and aim: Peripheral neuropathy is a disorder with often unknown causes. Some drugs, including statins, are proposed to be among the causes of peripheral neuropathy. This study aimed at evaluating this condition by electrodiagnostic study among patients who had received statins. Methods: This case-control study was conducted in Shiraz, Iran in 2015, and included 39 patients aged 35-55 who had received statins for at least 6 months, and 39 healthy matched controls. Using electrodiagnosis, the sensory and motor wave features (amplitude, latency and nerve conduction velocity) of the peripheral nerves (Median, Ulnar, Tibial, Sural, and Peroneal) were evaluated among the subjects. Data were analyzed using SPSS software and p

Since the outbreak of the new coronavirus, healthcare systems around the world have witnessed not only COVID-19 symptoms but also long-term complications of the aforementioned, including neurological problems. We report a clinical case of an adult patient with bilateral facial nerve palsy and progressive ascending paresis of the limbs after contracting the novel coronavirus (COVID-19). Additionally, the systematic review aimed to identify and summarize specific clinical features, outcomes and complications of the studies focusing on bilateral facial diplegia as a sequela of COVID-19 infection. The total number of analyzed patients was 15. Only one patient was diagnosed with isolated bilateral palsy; the rest had Guillain-Barré Syndrome (GBS). With one exception, all the presented cases had favorable outcomes, with facial palsy recovery from slight to almost complete. In patients with a confirmed COVID-19 diagnosis, bilateral facial palsy may be an isolated symptom as well as a variant of GBS. Symptoms of cranial nerve damage during a COVID-19 infection may explain the appearance of facial nerve damage. In order to clarify the spectrum of neurological manifestations and a causal relation between SARS-CoV-2, COVID-19 vaccination and neurological symptoms, direct attention towards the study of this virus is crucial. It seems reasonable to recognize human coronavirus as another potential GBS trigger.

Objective To report morbidity and oncological outcomes in a consecutive series of lateral isolated recurrent gynecological cancer involving the pelvic side wall (PSW) including the iliopsoas muscle. Material and methods We retrospectively evaluated a consecutive series between 6/2013 and 12/2015 of lateral isolated recurrent gynecological malignancies treated with a lateral endopelvic resection (LEPR). LEPR was defined as an en-bloc lateral resection of a pelvic tumor with sidewall muscle, and/or bone, and/or major nerve, and/or major vascular structure. Post-surgical complications, quality of life (QoL) and survivals were computed. Results Seventy-four women with pelvic isolated relapse were admitted for surgery during the study period. Among them, 8 cases (10.8%) showed lateral isolated relapse involving the iliopsoas muscle and were treated with LEPR. R0 resection was achieved in 6/8 patients (75.0%), while the pathologic margins were microscopically and macroscopically positive in 1 patient (12.5%), respectively. There were no perioperative mortalities. Major postoperative complications occurred in 3 patients (37.5%) through peripheral neuropathies, thrombosis of the vascular graft and compartment syndrome of the leg. Median follow-up time was 21 months (range, 12–28). The 2-year overall survival (OS) was 88% improving up to 100% if R0 resection was achieved. In patients with positive pathologic margins (n = 2), the 2-year OS was 50%. All women showed an improved QoL after surgery. Conclusion LEPR with iliopsoas resection can be safely performed in selected cases with lateral isolated gynecological relapse involving the PSW and was associated with improved QoL and prolonged survival when an R0 resection was achieved.

Peripheral neuropathies are frequently encourtered in clinical practice and are assiociated with a major impairment in quality of life . Howewvwr, their management reamans poor, and current therapies are often burdened with major side effects and can present poor efficacy on pain and functionality. Therefore, it has been suggested that the combination of two or more different drugs may improve analgesis efficacy and reduce side effects. Tricortin 1000 is formulated with 12 mg of Brain cortex phospholipid liposomes + 1000 microgrammi of Cyanocobalamin injectable (PL+ CNCb1) for intramuscolar use and is indicated in the tratment of poly-algo-neuropathic syndromes. This combination exerts a marked neurotrophic action by promoting the syntesis of endogenous phospholipids; moreover the peculiar formulation optimized the delivery of CNCb1 wich has analgesis and neurotrophic action. This paper discusses the pharmacotherapy of peripheral neuropathies, including low back pain, neck pain, post herpetic neuropathy (PHN) and focuses on the fixed dose combination PL+CNCb1 ckinical efficacy in association with other treatment or in monotherapy.

Introduction Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a debilitating autoimmune neuropathy that is treated with intravenous immunoglobulin (IVIG). The aim of this retrospective study was to investigate the efficacy and safety of the sucrose-free IVIG Octagam® (Octapharma AG, Lachen, Switzerland) in patients with CIDP. Methods Data from 47 patients who received at least one dose of Octagam were collected from the records of 11 centres in France. Efficacy was assessed using Overall Neuropathy Limitation Scale (ONLS). Safety was evaluated using adverse event rates. Results Data from 24 patients who were IVIG naïve (n = 11) or had stopped IVIG ≥ 12 weeks before initiation of Octagam therapy (washout group; n = 13) were included in the efficacy analysis. At 4 months post-initiation of Octagam treatment, 41.7% of patients had improved their functional status (decrease of ≥ 1 ONLS score) with a significant change in the ONLS score from baseline (– 0.42; p = 0.04; signed test). Functional status was reduced in only two patients: one patient in the IVIG-naïve group and one patient in the IVIG-washout group. All 47 patients were included in the safety analysis, which showed that Octagam was well tolerated, with a frequency of 0.04 adverse events per Octagam course. The most common adverse drug reaction was headache. Conclusions These real-life results are consistent with the efficacy and safety of IVIG reported in randomised controlled studies. A long-term prospective study of Octagam in patients with CIDP is warranted. Funding Octapharma, France SAS.

International audience; BACKGROUND:Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.METHODS:We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).RESULTS:At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P

Neuromuscular choristoma (NMC) is a very rare, developmental malformation characterized by the endoneurial intercalation of mature muscle fibers among peripheral nerve fibers. NMC typically arises in the major proximal peripheral nerves, most commonly the sciatic nerve, and may involve the lumbosacral and brachial plexus. Patients present clinically with progressive neuropathy or plexopathy. NMC is strongly associated with development of a fibromatosis, histologically identical to conventional desmoid-type fibromatosis (NMC-fibromatosis). The development of NMC-fibromatosis is often precipitated by iatrogenic trauma (ie, biopsy). Desmoid-type fibromatosis is characterized by CTNNB1 exon 3 mutations, which result in aberrant nuclear β-catenin localization and dysregulated canonical Wnt signaling. In contrast, the pathogenesis of NMC and NMC-fibromatosis is unknown. Desmoid-type fibromatosis expresses estrogen receptors (ER), specifically the ER-beta isoform (ERβ), and endocrine therapies may be used in surgically unresectable cases. In contrast, the ER expression profile of NMC-fibromatosis is unknown. We evaluated a series of NMC and NMC-fibromatosis for CTNNB1 mutations, β-catenin expression, and ER isoform expression. Five NMCs occurred in 2 female and 3 male patients (median age: 14 y, range T (p.S45F) and 1 c.121 A>G (p.T41A). Four patients subsequently developed NMC-fibromatosis, and all 4 cases contained CTNNB1 mutations, including 1 p.T41A and 3 p.S45F mutations. In 3 patients, the NMC and NMC-fibromatosis had identical CTNNB1 mutations. Only 1 NMC had no detectable CTNNB1 mutation; however, the patient's subsequent NMCfibromatosis had a CTNNB1 p.T41A mutation. All NMC and NMC-fibromatosis showed aberrant nuclear localization of β-catenin, nuclear ERβ expression, and no ERα expression. The presence of CTNNB1 mutations both in NMC and NMC-fibromatosis may be a shared molecular genetic abnormality underlying their pathogenesis.

AIM: This study aimed to confirm the role of f VEGF gene 936 C/T polymorphism and Diabetic Polyneuropathy (DPN) in the Indonesian population as well as to investigate its relationship with VEGF-A level and the role of vascular risk factors. MATERIAL AND METHODS: This was a cross-sectional study involving 152 subjects. Clinical symptoms and signs of DPN were examined using DNE and DNS scoring followed by nerve conduction study. All subjects underwent anthropometric, clinical examination and laboratory procedures to obtain body mass index, HbA1C level, lipid profile, Polymorphism of +936 C/T VEGF gene (PCR-RFLP technique), and VEGF-A plasma level (ELISA). Statistical analysis using a t-test or Mann-Whitney was performed to assess continuous data and Chi-square for categorical data. Multivariate logistic regressions were also performed to determine the relationship between independent variables and DPN. RESULTS: Sixty-nine (45.4%) fulfilled the diagnostic criteria of DPN. There was a significant association between CT + TT genotype and DPN (OR 0.35 95%CI 0.16-0.79 p = 0.01). Multivariate logistic regression showed that plasma VEGF-A level (OR = 1.003; 95% CI = 1.000-1.007; p = 0.03), diabetes duration (OR = 1.108; 95% CI = 1.045-1.175; p = 0.001), and CT+TT genotype (OR = 0.347; 95%CI = 0.148-0.817; p = 0.013) were associated with DPN. Sub-group analysis on subjects with HbA1C level ≥7% showed that VEGF-A (OR = 1.011; 95%CI = (1.004-1.017; p = 0.03), diabetes duration (OR = 1.245; 95% CI = 1.117-1.388; p < 0.001), CT + TT genotype (OR = 0.259; 95%CI = 0.074-0.911p = 0.035), with an adition of HDL (OR = 0.916; 95% CI = 0.857-0.978; p = 0.009) were significant predictors of DPN while LDL (OR = 1.017; 95% CI = 1.000-1.035; p = 0.053) acted as modifying factor. CONCLUSION: It appeared that CT + TT genotype of VEGF +936 gene might act as a protecting factor for DPN while VEGF-A, diabetes duration, HDL, and LDL acted as risk factors especially on subjects with HbA1C level ≥ 7.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect of cancer treatment; however, the effects of CIPN on the daily life of individuals are not completely understood. CIPN can be induced by several types of drugs that are widely used in the treatment of solid and hematological malignancies. Our knowledge of the mechanisms underlying CIPN is incomplete, but structural properties of the various neurotoxic compounds might contribute to variations in the pathogenetic mechanisms of damage, in addition to the type of neurotoxicity, severity of the clinical condition, and incidence of CIPN. No drugs capable of preventing the occurrence of CIPN or ameliorating its long-term course are available, and chemotherapy schedule modification is often required to limit its severity, which could potentially prevent patients from receiving the most effective treatment for cancer. Moreover, symptomatic therapy is often largely ineffective in reducing CIPN symptoms. In this Review, the mechanistic and clinical aspects of this unpredictable condition are considered, along with the controversial aspects of CIPN, including the onset mechanisms associated with the different drug types, assessment of the patient's condition, and the current status of neuroprotection and treatment options.

Carpal tunnel syndrome (CTS) is a musculoskeletal condition that often impairs the fitness to work. Our aim is to retrospectively evaluate the association between physical exposures in meat processing industry in Northern Italy and the CTS, taking into account non-occupational factors.A cross-sectional study was performed to include 434 workers (236 males, 198 females, 37.0±10.6 years old, working age: 12.6±10.8 years) from meat processing industries. Signs and symptoms were collected at the compulsory occupational medical surveillance. Occupational risk factors were assessed through a questionnaire and direct assessment by investigators. Adjusted odds ratios (ORDiagnosis of the CTS was reported for 61 out of 434 subjects (14.1%) for an incidence of 11.3/1000 person- years. In general, signs and symptoms for the CTS were associated with the following demographic factors: smoking history (OR = 1.909, 95% confidence interval (CI): 1.107-3.293), previous traumas of the upper limb (OR = 3.533, 95% CI: 1.743-7.165), hypothyroidism status (OR = 7.897, 95% CI: 2.917-21.38) and, in the case of female participants only, previous pregnancies (OR = 2.807, 95% CI: 1.200-6.566) as well as a personal history of oral contraceptive therapy and/or steroidal replacement therapy (OR = 11.57, 95% CI: 4.689-28.56). The carpal tunnel syndrome cases were associated with the following occupational factors (4 h/day): forceful hand exertion (ORIncreasing levels of hand activity and force were associated with the increased CTS prevalence among participants. Recommendations have to be provided in order to reduce occupational exposure to these risk factors and improve medical surveillance. Med Pr 2017;68(2):199-209.Carpal tunnel syndrome (CTS) is a musculoskeletal condition that often impairs the fitness to work. Our aim is to retrospectively evaluate the association between physical exposures in meat processing industry in Northern Italy and the CTS, taking into account non-occupational factors.A cross-sectional study was performed to include 434 workers (236 males, 198 females, 37.0±10.6 years old, working age: 12.6±10.8 years) from meat processing industries. Signs and symptoms were collected at the compulsory occupational medical surveillance. Occupational risk factors were assessed through a questionnaire and direct assessment by investigators. Adjusted odds ratios (ORDiagnosis of the CTS was reported for 61 out of 434 subjects (14.1%) for an incidence of 11.3/1000 person- years. In general, signs and symptoms for the CTS were associated with the following demographic factors: smoking history (OR = 1.909, 95% confidence interval (CI): 1.107–3.293), previous traumas of the upper limb (OR = 3.533, 95% CI: 1.743–7.165), hypothyroidism status (OR = 7.897, 95% CI: 2.917–21.38) and, in the case of female participants only, previous pregnancies (OR = 2.807, 95% CI: 1.200–6.566) as well as a personal history of oral contraceptive therapy and/or steroidal replacement therapy (OR = 11.57, 95% CI: 4.689–28.56). The carpal tunnel syndrome cases were associated with the following occupational factors (4 h/day): forceful hand exertion (ORIncreasing levels of hand activity and force were associated with the increased CTS prevalence among participants. Recommendations have to be provided in order to reduce occupational exposure to these risk factors and improve medical surveillance. Med Pr 2017;68(2):199–209.

Objectives The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. Methods In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. Results Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. Conclusions MTX may be effective and safe for remission-maintenance in AAV. Trial registration clinicaltrials.gov NCT00751517.

Peripheral neurotoxicity is a frequent complication limiting docetaxel chemotherapy in patients with cancer. We developed an experimental model that closely mimics the course of neuropathy in patients, aiming to investigate both the mechanisms of neurotoxicity at biochemical, functional and morphological levels and the potential neuroprotective role of neuroactive steroids. We demonstrated that treatment with dihydroprogesterone (DHP) or progesterone (P) counteracts docetaxel-induced neuropathy, preventing nerve conduction and thermal threshold changes, and degeneration of skin nerves in the foodpad. Neuroactive steroids also counteract the changes in gene expression of several myelin proteins and calcitonin gene-related peptide induced by docetaxel in sciatic nerve and lumbar spinal cord, respectively. Most nerve abnormalities observed during the treatment with docetaxel spontaneously recovered after drug withdrawal, similarly to what occurs in patients. However, results of midterm follow-up experiments indicated that animals cotreated with DHP or P have a faster recovery of the neuropathy compared with docetaxel-treated rats. Our study confirmed that neuroactive steroids exert a protective effect on peripheral nerves at different levels, suggesting that they might represent a new therapeutic frontier for patients with chemotherapy-induced neuropathy.

Background Increasing evidence suggests that the immune system has a beneficial role in the progression of amyotrophic lateral sclerosis (ALS) although the mechanism remains unclear. Recently, we demonstrated that motor neurons (MNs) of C57SOD1G93A mice with slow disease progression activate molecules classically involved in the cross-talk with the immune system. This happens a lot less in 129SvSOD1G93A mice which, while expressing the same amount of transgene, had faster disease progression and earlier axonal damage. The present study investigated whether and how the immune response is involved in the preservation of motor axons in the mouse model of familial ALS with a more benign disease course. Methods First, the extent of axonal damage, Schwann cell proliferation, and neuromuscular junction (NMJ) denervation were compared between the two ALS mouse models at the disease onset. Then, we compared the expression levels of different immune molecules, the morphology of myelin sheaths, and the presence of blood-derived immune cell infiltrates in the sciatic nerve of the two SOD1G93A mouse strains using immunohistochemical, immunoblot, quantitative reverse transcription PCR, and rotating-polarization Coherent Anti-Stokes Raman Scattering techniques. Results Muscle denervation, axonal dysregulation, and myelin disruption together with reduced Schwann cell proliferation are prominent in 129SvSOD1G93A compared to C57SOD1G93A mice at the disease onset, and this correlates with a faster disease progression in the first strain. On the contrary, a striking increase of immune molecules such as CCL2, MHCI, and C3 was seen in sciatic nerves of slow progressor C57SOD1G93A mice and this was accompanied by heavy infiltration of CD8+ T lymphocytes and macrophages. These phenomena were not detectable in the peripheral nervous system of fast-progressing mice. Conclusions These data show for the first time that damaged MNs in SOD1-related ALS actively recruit immune cells in the peripheral nervous system to delay muscle denervation and prolong the lifespan. On the contrary, the lack of this response has a negative impact on the disease course. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0732-2) contains supplementary material, which is available to authorized users.

Objectives Carpal tunnel syndrome (CTS) is the most common nerve entrapment syndrome, which since the beginning of the seventies has been linked to the keyboard and visual display unit (VDU). The objective of this study was to investigate the prevalence and personal factors associated with CTS in female VDU workers in Italy. Material and methods Participants in this study were female adult subjects, working ≥ 20 h/week (N = 631, mean age 38.14±7.81 years, mean working age 12.9±7.24 years). Signs and symptoms were collected during compulsory occupational medical surveillance. The binary logistic regression was used to estimate adjusted odds ratios for the factors of interest. Results Diagnosis of CTS was reported in 48 cases (7.6%, 11 of them or 1.7% after a surgical correction) for the incidence of 5.94/1000 person-years. In general, signs and symptoms of CTS were associated with the following demographic factors: previous trauma of upper limb (adjusted odds ratio (ORa) = 8.093, 95% confidence interval (CI): 2.347-27.904), history (> 5 years) of oral contraceptives therapy/hormone replacement therapy (ORa = 3.77, 95% CI: 1.701-8.354) and cervical spine signs/symptoms (ORa = 4.565, 95% CI: 2.281-9.136). Conclusions The prevalence of CTS was similar to the estimates for the general population of Italy. Among personal risk factors, hormone therapy, previous trauma of the upper limb and signs/symptoms of the cervical spine appeared to be associated with a higher risk of CTS syndrome. Eventually, the results reinforce interpretation of CTS in VDU workers as a work-related musculoskeletal disorder rather than a classical occupational disease. Int J Occup Med Environ Health 2016;29(6):927-936.

IMiDs compounds are a class of analogues of thalidomide, with greater immunomodulatory activity and a superior safety profile compared to the parent compound. They show substantial increase in potency and an interesting tolerability profile, primarily due to a decreased incidence of the most severe side effect of thalidomide, i.e. Chemotherapy-Induced Peripheral Neurotoxicity (CIPN). These novel aspects of the IMiDs compounds will be discussed.

Cisplatin, paclitaxel and bortezomib are effective chemotherapy drugs in cancer treatment. However, they share severe peripheral neurotoxicity (PN) as one of their major dose-limiting side effects, often impairing cancer patients' quality of life and sometimes being permanent. Even if preclinical oncology is largely based on the use of immune-deficient mice, rodent models used to study the chemotherapy-induced PN are available only in immune-competent animals. In this study we characterized for the first time the PN induced by these chemotherapies through neurophysiological, behavioral, morphological and morphometric studies in athymic nude mice, a commonly employed strain in the preclinical oncology. The animals, divided into four groups, were chronically treated with cisplatin, paclitaxel or bortezomib once or twice a week for 4 or 6. weeks or were left untreated. These schedules were tolerated, neurotoxic and in the range of antineoplastic effectiveness. Despite similarities, differences in the features of PN were evident if compared with immune-competent models under comparable regimens of treatment. The results of this study may provide a basis for future combined analysis of antineoplastic and neurotoxic effects of chemotherapy in the same animals.

Quantification of cutaneous innervation in rat footpad is a useful tool to investigate sensory small-diameter nerve fibers, which are affected early in peripheral neuropathies. The aim of this work was to provide normative reference data on the density of intraepidermal nerve fibers (IENFs) and Langerhans cells in the hindpaw footpad of Sprague-Dawley and Wistar rats. We also evaluated the sensibility of IENF density by comparing neuropathologic findings with neurophysiologic examination and the presence of peripheral neuropathy in two well-characterized animal models of neuropathy. IENF density was quantified in 22 Sprague-Dawley rats and 13 Wistar rats and compared with 19 age-matched Sprague-Dawley rats with streptozotocin-induced diabetic neuropathy and 30 age-matched Wistar rats with cisplatin- or paclitaxel-induced neuropathy. Antidromic tail sensory nerve conduction velocity (SNCV) was assessed in all animals. IENF and Langerhans cell densities were constant in healthy Sprague-Dawley rats at any age, and they were similar to those observed in healthy Wistar rats. In neuropathic rats, both SNCV and IENF density were significantly reduced with respect to controls. Quantification of IENF density was significantly correlated with changes in conduction velocity. Diabetic neuropathy rats alone showed a significantly higher density of Langerhans cells compared with controls. Our study demonstrated that IENF density quantification correlates with SNCV changes and suggests that this might represent a useful outcome measurement in experimental neuropathies. © 2005 Peripheral Nerve Society.