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Velasco R.,Hospital Universitari Of Bellvitge Ico Duran ynals | Velasco R.,Autonomous University of Barcelona | Videla S.,Laboratorios del Doctor Esteve S.A. | Villoria J.,Medicxact S.L. | And 3 more authors.
Acta Neurologica Scandinavica

Objectives: Thermal quantitative sensory testing (QST) is a non-invasive procedure helpful in the assessment of the function of small Aδ and C nerve sensory fibres. Oxaliplatin (OXA) is an effective chemotherapeutic agent, but is frequently associated with neurotoxic dose-limiting side effects. This controlled clinical trial evaluated the reliability and accuracy of thermal QST for assessing the OXA-induced acute neuropathic syndrome, whose clinical hallmark is cold-triggered painful paraesthesia. Materials & methods: A testing protocol with the Thermal Sensory Analyzer (Medoc) was carried out in 20 colorectal cancer patients during the initial four cycles of OXA-based chemotherapy and in 20 age- and sex-matched healthy volunteers. Testing was carried out on the hands and included the determination of thermal detection and pain thresholds and the intensity of pain evoked by cold stimuli. Calculations were made of: coefficients of test-retest and inter-rater reliability, indices of responsiveness and parameters that quantify diagnostic accuracy. Results: Thermal thresholds showed moderate to good reliability (ρ ≥ 0.383), but were not consistently responsive to the effects of chemotherapy (cold pain thresholds decreased in both groups, although almost twice in patients compared to healthy volunteers). Conversely, the intensity of pain evoked by suprathreshold cold stimuli was reliable (ρ ≥ 0.822), responsive (detected changes over time) and discriminated between patients and healthy volunteers (area under the ROC curve = 0.700). Conclusions: The procedure was reliable and accurate to evaluate cold hyperalgesia resulting from OXA administration. The data provided may be used to define efficacy endpoints for future clinical trials of therapies for OXA-induced neuropathies and calculate appropriate sample sizes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Argyriou A.A.,Saint Andrews State General Hospital of Patras | Argyriou A.A.,University of Patras | Cavaletti G.,University of Milan Bicocca | Bruna J.,Hospital Universitari Of Bellvitge Ico Duran ynals | And 2 more authors.
Archives of Toxicology

This review paper provides a critical exploration of updates concerning the spectrum of characteristics and treatment options of bortezomib-induced peripheral neuropathy (BIPN). Emphasis is given on pathogenesis issues. Although the mechanism underlying BIPN still remains elusive, it is increasingly acknowledged that the inhibition of proteasome activity in dorsal root ganglia and peripheral nerves, the mitochondrial-mediated disruption of Ca++ intracellular homeostasis and the disregulation in nuclear factor κB and brain-derived neurotrophic factor play a significant pathogenic role. Assessment of BIPN is based on comprehensive grading scales, using a combination of "subjective" and "objective" parameters, which turn out to be ambiguously interpreted, thus leading to both under- and misreporting of its true incidence and severity. BIPN is clinically defined as a typical example of a dose-dependent, distally attenuated painful, sensory neuronopathy. Patients pre-treated with neurotoxic regimens and those with pre-existing neuropathy are more likely to develop severe neurotoxicity. To date, there is no effective pharmacological treatment to prevent BIPN, and therefore, interventions remain merely symptomatic to focus on the alleviation of neuropathic pain. Hence, strict adherence to the dose reduction and schedule change algorithm is recommended in order to prevent treatment-emergent BIPN and allow the continuation of treatment. Further studies in animal models and humans, including experimental, clinical, neurophysiological and pharmacogenetic approaches, are needed to allow the identification of the true spectrum of BIPN pathogenesis and characteristics. It is expected that such comprehensive approaches would be the starting point for the development of early preventive and therapeutic interventions against BIPN. © 2014 Springer-Verlag. Source

Velasco R.,Hospital Universitari Of Bellvitge Ico Duran ynals | Velasco R.,Autonomous University of Barcelona | Bruna J.,Hospital Universitari Of Bellvitge Ico Duran ynals | Bruna J.,Autonomous University of Barcelona
Current Colorectal Cancer Reports

Oxaliplatin (OXA) is a first-line agent in the systemic treatment of colorectal cancer (CRC). OXA-induced neuropathy is the most prominent adverse effect, both during and after the completion of chemotherapy. OXA neurotoxicity (OXA-NTX) is a dose-limiting, frequent, and long-lasting adverse event that may compromise therapeutic outcome and the quality-of-life of CRC patients. Increased knowledge of the pathophysiology and clinical profile of this neuropathy is being achieved. Two types of neuropathy are usually observed, and evidence suggests a link between the acute symptoms and the development of chronic NTX. In this paper we review the main advances and the outstanding issues concerning OXA-NTX, for example calcium/magnesium and other drugs in the prophylaxis and treatment of this neuropathy. Recently available and ongoing investigation of pharmacogenomics, clinical and neurophysiological risk factors, and early markers of OXA-NTX are of great value in clinical decision-making, contributing to minimizing the risk of severe neuropathy. © 2014 Springer Science+Business Media New York. Source

Izquierdo C.,Hospital Universitari Of Bellvitge Ico Duran ynals | Velasco R.,Hospital Universitari Of Bellvitge Ico Duran ynals | Velasco R.,Autonomous University of Barcelona | Vidal N.,Hospital Universitari Of Bellvitge Ico Duran ynals | And 6 more authors.

Background. Primary central nervous system lymphomas may present as diffuse, nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis cerebri (LC). We did a systematic review and analysis of the literature, adding our own cases, to better characterize LC in order to improve early diagnosis and treatment. Methods. PubMed, ISI Web of Knowledge, and hospital databases were reviewed. Information was extracted regarding demographic, clinical, histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables. The impact of single parameters on overall survival (OS) was determined by applying univariate and multivariate analyses. Results. Forty-two patients were included (median age: 58 y; range: 28-80 y). At consultation, 52% of patients had a poor KPS. The most common presenting symptom was cognitive decline (59.5%). Imaging studies showed supratentorial and infratentorial infiltration in 55% of patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1-30) months, and the diagnosis was not established until autopsy for 33% of patients. The median OS was 2.95 (range: 0.33-56) months; however, those patients who received methotrexate had a median OS of 13.8 (range: 0.7-56) months. Analysis identified KPS ≥ 70 (HR: 0.32; 95% CI: 0.114-0.894; P =. 03) and treatment with methotrexate (HR: 0.19; 95% CI: 0.041-0.886; P =. 034) as independent favorable prognostic factors, whereas T-cell lymphoma was independently related with a worse outcome (HR: 6.62; 95% CI: 1.317-33.316; P =. 022). Conclusions. LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS. © 2015 The Author(s). Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. Source

Briani C.,University of Padua | Argyriou A.A.,Saint Andrews State General Hospital of Patras | Argyriou A.A.,University of Patras | Izquierdo C.,Hospital Universitari Of Bellvitge Ico Duran ynals | And 11 more authors.
Journal of the Peripheral Nervous System

This prospective study sought to identify the potential reversibility of oxaliplatin-induced peripheral neuropathy (OXAIPN) by following-up its long-term course 2 years after discontinuation of oxaliplatin (OXA)-based chemotherapy. Participants were 91 colorectal cancer patients treated with OXA-based chemotherapy. Neurological assessment, clinical Total Neuropathy Score© (TNSc©) and nerve conduction studies were performed at baseline (T0), the end of chemotherapy (T1) and 2 years (T2) after discontinuation of chemotherapy. A total of 73 of 91 (80%) patients experienced OXAIPN at T1. At a median follow-up of 25 months, persistence of chronic OXAIPN was present in 61 of 73 patients (84%) and complete resolution was present in 12 patients (17%). Longitudinal comparison of TNSc© values between T1 and T2 revealed that the overall severity of OXAIPN in those 61 patients significantly decreased over time. Median TNSc© values were nine (range: 2-15) at T1 vs. four (range: 2-12) at T2 (P < 0.001). Likewise, sensory nerve conduction measures at T2 significantly improved in all sensory nerves tested, compared with T1. Severity of OXAIPN at T2 was significantly associated (P < 0.001) with high severity of OXAIPN at T1. In conclusion, persistence of OXAIPN beyond 2 years after finishing chemotherapy is common. Clinical and neurophysiological improvement is observed, although recovery is often incomplete. © 2015 Peripheral Nerve Society. Source

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