Elisabeth Chroni

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.

Vitamin E for prophylaxis against chemotherapy-induced neuropathy: A randomized controlled trial

Background: The authors conducted a pilot, randomized, open label with blind assessment, controlled trial to determine whether vitamin E supplementation has a neuroprotective effect in chemotherapy-induced peripheral nerve damage. Methods: Thirty-one patients with cancer treated with six courses of cumulative cisplatin, paclitaxel, or their combination regimens were randomly assigned in two groups and followed by neurologic examination and electrophysiologic study. Patients assigned in Group I (n = 16) received oral vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of Group II (n = 15), who received no supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified peripheral neuropathy score. Results: The incidence of neurotoxicity differed between the two groups, occurring in 4/16 (25%) patients assigned in the vitamin E supplementation group and in 11/15 (73.3%) patients assigned in the control group (p = 0.019). Mean peripheral neuropathy scores were 3.4 ± 6.3 for patients of Group I and 11.5 ± 10.6 for patients of Group II (p = 0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of control patients, RR = 0.34, 95% CI = 0.14 to 0.84. Conclusion: Vitamin E supplementation in cancer patients may have an important neuroprotective effect.

F-waves in clinical neurophysiology: a review, methodological issues and overall value in peripheral neuropathies

This report comments on methodological issues related to the use of F-wave in clinical neurophysiology. An F-wave study aims to describe with relative accuracy the properties of the compound F-wave population which is the population of F-waves consecutively recorded from a muscle. This can only be achieved if an adequate number of F-waves is sampled. In order to avoid inaccuracies, correction of F-wave latency measurements for height or limb length and age is also required. Differences in the recording procedure could account for the variability in F-wave measurements. The usefulness of F-wave parameters other than latency is discussed. F-chronodispersion and F-tacheodispersion are more sensitive than conventional neurophysiological methods in detecting mild nerve lesions. F-persistence provides valuable information only if the findings are interpreted in correlation with the particular clinical setting. The suitability of the F-wave technique for routine studies is examined and a current view on the clinical applications is briefly recounted. There is an urgent need for the standardization of F-wave methodology.

Focal Electroencephalographic Abnormalities in Juvenile Myoclonic Epilepsy

Summary: A detailed study of EEGs of patients with an unequivocal diagnosis of juvenile myoclonic epilepsy (JME) showed a high prevalence of focal EEG abnormalities. Focal slow waves, spikes, and sharp waves and focal onset of the generalized discharge were present in 36.7% of EEGs in our patients with JME. In more than half of the patients, at least one EEG showed focal abnormalities. These features should not be misconstrued as indicative of partial epilepsy.

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.

Deep brain stimulation for secondary dystonia: results in 8 patients

BackgroundDystonia is a medically intractable condition characterized by involuntary twisting movements and/or abnormal postures. Deep Brain Stimulation (DBS) has been used successfully in various forms of dystonia. In the present study, we report on eight patients with secondary dystonia, treated with DBS in our clinic.MethodEight patients (five males, three females) underwent DBS for secondary dystonia. The etiology of dystonia was cerebral palsy (n = 2), drug-induced (n = 1), post encephalitis (n = 2) and postanoxic dystonia (n = 3). The functional capacity was evaluated before and after surgery with the use of Burke-Fahn-Mardsen Dystonia Rating Scale (BFM scale), both movement and disability scale (MS and DS, respectively). The target for DBS was the globus pallidus internus (GPi) in 7 patients and in one patient, with postanoxic damaged pallidum, the ventralis oralis anterior (Voa) nucleus. Brain perfusion scintigraphy using Single Photon Emission Computed Tomography (SPECT) was performed in two separate studies for each patient, one in the “off-DBS” and the other in the “on-DBS” state.FindingsPostoperative both MS and DS scores were found to be significantly lower compared to preoperative scores (p = 0.018 and p = 0.039, respectively). Mean improvement rate after DBS was 41.4% (0 – 94.3) and 29.5% (0 – 84.2) in MS and DS scores, respectively. The SPECT Scan, during the “on-DBS” state, showed a decrease in regional cerebral blood flow (rCBF), compared to the “off-DBS” state.ConclusionsOur results seem promising in the field of secondary dystonia treatment. More studies with greater number of patients and longer follow-up periods are necessary in order to establish the role of DBS in the management of secondary dystonia. Finally, the significance of brain SPECT imaging in the investigation of dystonia and functional effects of DBS should be further evaluated.

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.

The effect of vascular disease on late onset Parkinson's disease

The clinical severity of late onset Parkinsons disease (PD) varies from patient to patient and it is further complicated by the increasing prevalence of accompanying disorders in the elderly. We set out to study the impact of ischemic heart disease, minor stroke, hypertension and diabetes mellitus in a group of late onset PD patients (age ≥70 years). Consecutive late onset PD patients seen in the Department of Neurology, Medical School of Patras, Greece were included in this study. We used very strict criteria to eliminate the possibility of including patients with vascular parkinsonism. Comparisons were made between groups of patients suffering with idiopathic Parkinsons disease (IPD) and the above‐mentioned diseases. One hundred and sixty‐seven consecutive late onset PD patients were included in this study. The most common accompanying disorders in our group were hypertension in 31 (18%) of the patients and minor stroke in 20 (12%). The Hoen and Yahr score in late onset IPD patients who suffered from minor stroke, ischemic heart disease or diabetes mellitus was significantly higher when compared with patients without the above disorders. The results clearly suggest that the presence of vascular disease on an IPD patient may aggravate PD severity. In clinical grounds, these findings can be proved significant since early and aggressive prevention of vascular disease and treatment of vascular risk may contribute in controlling symptom severity in PD.

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.

Vegetative State and Minimally Conscious State: A Review of the Therapeutic Interventions

Background/Aims: The purpose of the present article is a systematic review of the proposed medical or surgical treatments in patients in chronic vegetative state (VS) or minimally conscious state (MCS), as well as of their mechanisms of action and limitations. Methods: For this review, we have agreed to include patients in VS or MCS having persisted for over 6 months in posttraumatic cases, and over 3 months in nontraumatic cases, before the time of intervention. Searches were independently conducted by 2 investigators between May 2009 and September 2009 in the following databases: Medline, Web of Science and the Cochrane Library. The electronic search was complemented by cross-checking the references of all relevant articles. Overall, 16 papers were eligible for this systematic review. Results: According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. Conclusion: The treatments proposed for disorders of consciousness have not yet gained the level of ‘evidence-based treatments’; moreover, the studies to date have led to inconclusiveness. The published therapeutic responses must be substantiated by further clinical studies of sound methodology.