العصب تقييم الإثارة في العلاج الكيميائي الناجم عن العصبية
Summary
هذا الملخص يصف طريقة جديدة لتقييم تطور العصبية في المرضى الذين يتلقون العلاج الكيماوي. في حين تقتصر وسائل التقييم التقليدية في قدرتها على الكشف عن التغييرات في وقت مبكر في وظيفة العصب، وتقنيات استثارة العصب توفير التعرف المبكر على المرضى المعرضين للخطر من العصبية الشديدة والتبصر في الفيزيولوجيا المرضية.
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
الناجم عن العلاج الكيماوي الاعتلال العصبي هو أحد الآثار الجانبية الخطيرة لعلاج السرطان، والتي قد تؤثر على مسار العلاج وطويلة الأمد عجز المريض. هناك عدم وجود تدابير تقييم حساسة وموضوعية لقياس تحديدا خلل الأعصاب لدى مرضى العلاج الكيميائي العلاج. وقد وفرت التنمية السريرية لتقنيات استثارة محواري معلومات مفيدة والتنبؤية لتقييم العلاج الكيميائي الناجم عن العصبية. من خلال توفير المعلومات حول وظيفة القناة الايونية، وإمكانات يستريح، ومحور عصبي وظيفة الغشاء، وهذه التقنيات تمكن التبصر في العمليات الفيزيولوجية المرضية الكامنة وراء الخلل في محواري مرضى السرطان للعلاج الكيماوي. وبالإضافة إلى ذلك، ثبت عمليا أن تقنيات استثارة محواري أن يكون ذلك ممكنا في وضع علم الأورام السريرية، ويمكن الانتهاء من اختبار واحد في 5-10 دقائق.
في اوكزالبلاتين المرضى الذين عولجوا، وتقنيات توفير استثارة محواريالعلامات البيولوجية الحساسة التي يمكن التعرف المبكر على المرضى المعرضين للخطر من العصبية الشديدة. بالمقارنة مع التقليدية دراسات التوصيل العصبي الذي يحدد اوكزالبلاتين الناجم عن تلف الأعصاب فقط بعد خسارة محواري حدث بالفعل، والدراسات استثارة محواري توفير علامات تنبئ عن ضعف العصب قبل فقدان محور عصبي. على هذا النحو، يمكن استخدام دراسات استثارة محواري لتقديم تقييم وظيفة العصب في التجارب السريرية لاستراتيجيات اعصاب محتمل، لتحديد فعالية بموضوعية اعصاب.
Disclosures
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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