कीमोथेरेपी प्रेरित neurotoxicity में तंत्रिका excitability आकलन
Summary
इस सार के लिए रसायन चिकित्सा उपचार प्राप्त रोगियों में न्यूरोटॉक्सिटी के विकास का आकलन करने के लिए एक उपन्यास विधि का वर्णन करता है. जबकि पारंपरिक मूल्यांकन विधियों उनके तंत्रिका समारोह में प्रारंभिक परिवर्तन का पता लगाने की क्षमता में सीमित कर रहे हैं, तंत्रिका excitability तकनीक गंभीर और pathophysiology में न्यूरोटॉक्सिटी अंतर्दृष्टि के जोखिम में रोगियों की जल्दी पहचान प्रदान करते हैं.
Abstract
Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies1,2. Chemotherapy-induced peripheral neuropathy produces symptoms of numbness and paraesthesia in the limbs and may progress to difficulties with fine motor skills and walking, leading to functional impairment. In addition to producing troubling symptoms, chemotherapy-induced neuropathy may limit treatment success leading to dose reduction or early cessation of treatment. Neuropathic symptoms may persist long-term, leaving permanent nerve damage in patients with an otherwise good prognosis3. As chemotherapy is utilised more often as a preventative measure, and survival rates increase, the importance of long-lasting and significant neurotoxicity will increase.
There are no established neuroprotective or treatment options and a lack of sensitive assessment methods. Appropriate assessment of neurotoxicity will be critical as a prognostic factor and as suitable endpoints for future trials of neuroprotective agents. Current methods to assess the severity of chemotherapy-induced neuropathy utilise clinician-based grading scales which have been demonstrated to lack sensitivity to change and inter-observer objectivity4. Conventional nerve conduction studies provide information about compound action potential amplitude and conduction velocity, which are relatively non-specific measures and do not provide insight into ion channel function or resting membrane potential. Accordingly, prior studies have demonstrated that conventional nerve conduction studies are not sensitive to early change in chemotherapy-induced neurotoxicity4-6. In comparison, nerve excitability studies utilize threshold tracking techniques which have been developed to enable assessment of ion channels, pumps and exchangers in vivo in large myelinated human axons7-9.
Nerve excitability techniques have been established as a tool to examine the development and severity of chemotherapy-induced neurotoxicity10-13. Comprising a number of excitability parameters, nerve excitability studies can be used to assess acute neurotoxicity arising immediately following infusion and the development of chronic, cumulative neurotoxicity. Nerve excitability techniques are feasible in the clinical setting, with each test requiring only 5 -10 minutes to complete. Nerve excitability equipment is readily commercially available, and a portable system has been devised so that patients can be tested in situ in the infusion centre setting. In addition, these techniques can be adapted for use in multiple chemotherapies.
In patients treated with the chemotherapy oxaliplatin, primarily utilised for colorectal cancer, nerve excitability techniques provide a method to identify patients at-risk for neurotoxicity prior to the onset of chronic neuropathy. Nerve excitability studies have revealed the development of an acute Na+ channelopathy in motor and sensory axons10-13. Importantly, patients who demonstrated changes in excitability in early treatment were subsequently more likely to develop moderate to severe neurotoxicity11. However, across treatment, striking longitudinal changes were identified only in sensory axons which were able to predict clinical neurological outcome in 80% of patients10. These changes demonstrated a different pattern to those seen acutely following oxaliplatin infusion, and most likely reflect the development of significant axonal damage and membrane potential change in sensory nerves which develops longitudinally during oxaliplatin treatment10. Significant abnormalities developed during early treatment, prior to any reduction in conventional measures of nerve function, suggesting that excitability parameters may provide a sensitive biomarker.
Protocol
Discussion
कीमोथेरेपी प्रेरित न्युरोपटी कैंसर के इलाज की एक गंभीर पक्ष प्रभाव है, जो इलाज के पाठ्यक्रम को प्रभावित और लंबे समय तक चलने वाले रोगी विकलांगता का उत्पादन हो सकता है. संवेदनशील और उद्देश्य आकलन करने के लिए विशेष रूप से रसायन चिकित्सा रोगियों का इलाज में तंत्रिका शिथिलता को मापने के उपायों की कमी है. axonal excitability तकनीक के नैदानिक विकास कीमोथेरपी प्रेरित न्यूरोटॉक्सिटी के आकलन के लिए उपयोगी और भविष्य कहनेवाला जानकारी प्रदान की गई है. आयन चैनल समारोह, आराम संभावित, और axonal झिल्ली समारोह के बारे में जानकारी प्रदान करके, इन तकनीकों pathophysiological कैंसर कीमोथेरपी के साथ इलाज के रोगियों में axonal रोग के अंतर्निहित प्रक्रियाओं में के अंतर्दृष्टि सक्षम. इसके अलावा, axonal excitability के तकनीक के लिए नैदानिक ऑन्कोलॉजी सेटिंग में संभव हो गया है का प्रदर्शन किया है, और एक टेस्ट मैच 5-10 मिनट में पूरा किया जा सकता है.
Oxaliplatin रोगियों का इलाज में, axonal excitability तकनीक उपलब्ध कराने केसंवेदनशील biomarker जिसे गंभीर न्यूरोटॉक्सिटी के जोखिम में रोगियों की जल्दी पहचान के लिए सक्षम बनाता है. Axonal नुकसान के बाद ही oxaliplatin प्रेरित तंत्रिका क्षति की पहचान पारंपरिक तंत्रिका चालन अध्ययन की तुलना में पहले से ही हुआ है, axonal excitability के अध्ययन तंत्रिका रोग की पेशीनगोई मार्करों पूर्व प्रदान axonal नुकसान. जैसे, axonal excitability के अध्ययन के लिए संभावित neuroprotective रणनीतियों के नैदानिक परीक्षणों में तंत्रिका समारोह का मूल्यांकन प्रदान करने के लिए, निष्पक्ष neuroprotective प्रभावकारिता निर्धारित करने के लिए उपयोग किया जा सकता है.
Divulgations
The authors have nothing to disclose.
Materials
| Equipment and Materials | Company |
| QTracS program | Digitimer, Institute of Neurology, Queen Square, UK |
| DS5 isolated linear bipolar constant current stimulator | Digitimer |
| Sapphire IIA Amplifier | Medelec |
| Humbug 50/60 Hz Noise eliminator | Quest Scientific Instruments |
| Non-polarizable electrodes | Unomedical |
| Electrosurgical neutral earth plate | Unomedical |
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