Panagiotis Polychronopoulos

A review on oxaliplatin-induced peripheral nerve damage

Platinum compounds are a class of chemotherapy agents that posses a broad spectrum of activity against several solid malignancies. Oxaliplatin (OXL) is a third-generation organoplatinum compound with significant activity mainly against colorectal cancer (CRC). Peripheral neuropathy is a well recognized toxicity of OXL, usually resulting in dose modification. OXL induces two types of peripheral neuropathy; acute and chronic. The acute oxaliplatin-induced peripheral neuropathy (OXLIPN) may be linked to the rapid chelation of calcium by OXL-induced oxalate and OXL is capable of altering the voltage-gated sodium channels through a pathway involving calcium ions. On the other hand, decreased cellular metabolism and axoplasmatic transport resulting from the accumulation of OXL in the dorsal root ganglia cells is the most widely accepted mechanism of chronic oxaliplatin-induced peripheral neuropathy (OXLIPN). As a result, OXL produces a symmetric, axonal, sensory distal primary neuronopathy without motor involvement. The incidence of OXLIPN is usually related to various risk factors, including treatment schedule, dosage, cumulative dose and time of infusion. The assessment of OXLIPN is primarily based on neurologic clinical examination and quantitative methods, such as nerve conduction study. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested for their ability to prevent OXLIPN. However, the clinical data are still controversial. We herein review and discuss the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of OXLIPN. We also highlight areas of future research.

Family history of stroke in stroke types and subtypes

Many studies have provided data showing that family history of stroke (FHS) is associated with an increased risk of stroke. The association of the FHS with the various stroke subtypes has not been adequately studied. The purpose of this study was to assess the association of the FHS with the two major stroke types (cerebral haematomas and ischaemic strokes) and the four stroke subtypes (cardioembolic, large artery disease, small artery disease, and undetermined) in a Greek population. The FHS was obtained from 421 consecutive acute stroke patients and from 239 matched control subjects. Positive FHS was observed in 49% of all stroke patients compared with 28% of the control subjects [adjusted OR=2.06 (95% confidence intervals (CI) 1.42-3.00)]. Haematomas, ischaemic strokes, and from the ischaemic strokes, both large and small artery disease strokes were strongly associated with positive FHS compared with the control subjects [adjusted OR=2.06 (95% CI 9-3.04), 2.07 (95% CI 1.09-3.91), 2.05 (95% CI 1.24-3.38), and 2.76 (95% CI 1.55-4.91), respectively]. There was no difference between maternal and paternal heritable contribution.In conclusion, FHS was found in this study to be an independent risk factor for all strokes combined, for each stroke type, and for the large and small-artery disease stroke subtypes, but not for the cardioembolic and undetermined stroke subtypes.

Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy

We conducted a randomized, open-label, controlled trial to assess the efficacy of oxcarbazepine for prophylaxis against oxaliplatin-induced peripheral neuropathy (OxIN). Thirty-two patients with colon cancer received 12 courses of the FOLFOX-4 regimen and were randomly assigned to receive oxcarbazepine (600 mg BID) or chemotherapy without oxcarbazepine. The incidence of OxIN was strikingly decreased in patients receiving oxcarbazepine (31.2% vs 75%). Oxcarbazepine may prevent OxIN symptoms. Further larger placebo-controlled trials are warranted to confirm our results.

Incidence and characteristics of peripheral neuropathy during oxaliplatin-based chemotherapy for metastatic colon cancer

Aim. The current prospective study sought to trace the incidence and severity of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical and electrophysiological pattern. Patients and methods. Twenty-five adult patients scheduled to be treated with 12 courses of the oxaliplatin-based regimen, FOLFOX-4, for metastatic colon cancer participated in this study. Patients were clinically and electrophysiologically monitored at baseline and followed-up during chemotherapy. The severity of OXLIPN was summarized by means of a modified Total Neuropathy Score (TNS). Results. Evidence of OXLIPN was disclosed in 16 of the 25 patients (64%). The mean TNS values for patients manifesting some grade of OXLIPN were 13.9±5.8 (range 7–28). All longitudinal comparisons concerning the motor conduction parameters failed to reach significance. By contrast, comparisons of the median changes at baseline and each of the follow-up studies revealed significant decrease in all sensory action potentials examined. Conclusion. Our results indicate that the majority of patients treated with the FOLFOX-4 regimen would manifest an axonal, predominately sensory peripheral neuropathy, of mild to moderate severity.

Peripheral neuropathy induced by administration of cisplatin- and paclitaxel-based chemotherapy. Could it be predicted?

GoalThe goal of this study was to investigate the potential role of clinical and electrophysiological signs of chemotherapy-induced neurotoxicity (CIPN) in predicting the final outcome of CIPN.Patients and methodsWe prospectively studied 46 cancer patients treated with paclitaxel, cisplatin, or their combination-containing regimens for a nonmyeloid malignancy. The clinical evaluation of neuropathy was based on the modified Neurological Symptom and Neurological Disability Scores. Neurophysiological examination was also carried out. The battery of clinical and electrophysiological tests was repeated at the third and sixth courses of chemotherapy and up to 3 months after its cessation. Results of the clinical and electrophysiological study were summarized by means of a modified peripheral neuropathy (PNP) score.ResultsPatients were divided according to the PNP scores obtained at follow-ups into those with better outcome (group 1, PNP <14, n=19) and those with worse outcome (group 2, PNP >15, n=27). In each patient and before the maximum severity of CIPN had been reached, the incidence of clinical and electrophysiological variables was determined and compared between groups. After univariate analysis two variables from the clinical evaluation and one from the neurophysiological evaluation were related to higher severity of CIPN and thus with worse outcome. Multivariate regression analysis defined only one of them, namely, the decrease sural a-SAP >50% of the baseline value, as being the sole, significant predictor of worse neurological outcome.ConclusionOur study indicates that a precise clinical evaluation combined with a detailed electrophysiological evaluation could predict the final neurological outcome of the cisplatin- or/and paclitaxel-based chemotherapy.

Lunar phases and seizure occurrence: Just an ancient legend?

The authors retrospectively reviewed all neurologic records of an emergency unit from 1999 to 2003 to identify a potential association between lunar phases and seizure occurrence. Overall 859 patients admitted for seizure occurrence were divided into the four quarters of the synodic month according to moon phases. A significant clustering of seizures around the full moon period was observed, supporting the ancient belief of periodic increased seizure frequency during full-moon days.

Clinical and epidemiological features of motor neuron disease in south‐western Greece

Objective –  To evaluate the epidemiological and clinical features of motor neuron disease (MND) in a region (835,000 inhabitants) of south‐western Greece.

Factors associated with poor compliance of patients with epilepsy driving restrictions

The authors sought to identify factors associated with poor compliance with driving restrictions due to a diagnosis of epilepsy. They compared the demographic and clinical characteristics of 60 patients with epilepsy who, despite the authors’ recommendation, continued to drive, with those of 60 age- and sex-matched epileptic patients who refrained from driving. The results showed that patients with epilepsy do not comply with driving restrictions, mainly for employment-related reasons.

Paclitaxel plus carboplatin-induced peripheral neuropathy. A prospective clinical and electrophysiological study in patients suffering from solid malignancies.

ObjectiveThe current study intended to determine the incidence, severity and reversibility of paclitaxel plus carboplatin (CP)–induced peripheral neuropathy (CPPN) and to describe its clinical and electrophysiological features.Patients and methodsWe prospectively studied 21 adult patients scheduled to be treated with 6 courses of cumulative carboplatin plus paclitaxel (CP) regimens for a non–myeloid malignancy. They were followed–up by neurological examination and electrophysiological study during chemotherapy and 3 months after its discontinuation. The severity of neurotoxicity was assessed by means of a modified peripheral neuropathy (PNP) score.ResultsEvidence of CPPN was recorded in 14 of the 21 patients (66.6 %). The sensory symptoms were present in the lower limbs first and then involved the upper limbs. No statistical significance, concerning the changes from baseline to subsequent mean scores in all motor conduction parameters examined,was revealed. By contrast, comparisons of the mean changes at baseline and each of the follow–up studies showed significant decrease in all sensory action potentials examined. The mean PNP scores for patients that manifested some grade of neurotoxicity were 17.9 ± 9.8. The followup data 3 months after the discontinuation of chemotherapy showed that the CP–induced neuropathy was at least partially reversed.ConclusionsCP–induced neuropathy was symmetrical, distal and predominately sensory in character, though minor to moderate motor signs were only evident in severely affected patients. Reversibility of CPinduced neuropathy was partially observed after the suspension of chemotherapy.

The Association of Stroke with Life Events

The association of stressful life events with stroke was examined in a prospective controlled study which included 84 consecutive stroke patients and a comparison group of 84 control cases. The result