الفهرس 
Anatomy of the Peripheral Nervous SystemOnly 14 pages are availabe for public view
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Abstract
Peripheral neuropathy is the most common neurological complication of cancer. The differential diagnosis of peripheral nervous system dysfunction in cancer patients is broad and includes: direct nerve compression or infiltration by tumor, indirect tumour effects (paraneoplastic effects), neurotoxicity of cancer treatment, nutritional deficiencies, metabolic derangements and other co-morbidities.
Cancer could compress or invade nerves, causing ”neuropathic pain”. In a cancer microenvironment, cancer invading the nerves, with the surrounding immune cells secreting inflammatory mediators, sensitizes afferent nociceptors which increases spontaneous activity of the nerve and pain. This could be discovered by radiological imaging and treatment should address the tumour itself (e.g. chemotherapy, radiotherapy) and meanwhile symptomatic treatment should be received for pain management.
A peripheral neuropathy is defined as paraneoplastic when no causes could be detected (by exclusion) or when cancer-related immunological mechanisms are incriminated where a cross-reaction against antigens shared by the tumour and nervous system cells takes place. A classical example is sensory neuropathy in patients with SCLC and is typically associated anti-Hu antibody (Hu-Ab) and less frequently with anti-CV2/CRMP-5 antibodies (CV2/CRMP5-Ab) which strongly supports the diagnosis of paraneoplastic syndrome. The presence of neuronal anti-Hu paraneoplastic antibodies in thymoma patients is very rare.
Beyond treatment of the underlying tumor, immune modulation is a key component of paraneoplastic neuropathy therapy. Specific modalities include corticosteroids, corticosteroid-sparing agents (e.g. azathioprine, cyclophosphamide), the antiCD20 monoclonal antibody Rituximab, IV immunoglobulin (IVIG), and plasmapheresis.
Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect of many commonly used chemotherapeutic agents.
In the majority of the patients CIPN is reversible if recognized early enough and the treatment is discontinued or the dose is reduced. However, recovery may take months or even years.
Knowing chemotherapeutic dose limits is crucial to predict the onset of peripheral neuropathy:
Paclitaxel causes peripheral neurotoxicity at doses >175 mg/m2 which is mainly sensory. Docetaxel-induced neuropathy is not common when using therapeutic doses and is usually mild and disappears on drug discontinuation.
Usual vincristine dose is 1.4 mg/m2 per single dose with an upper limit of 2 mg for single doses. The earliest symptoms of neuropathy develop after 5-6 mg, but considerable toxicity is commonly not seen below the cumulative dose of 15-20 mg. Nearly all patients develop some degree of neuropathy during the treatment and the neuropathy is still progressing (“coasting”) in every third patient after discontinuation of the treatment.
It’s not common to encounter peripheral neurotoxicity with the other vinca alkaloids like vincristine and it’s usually mild and reversible.
Peripheral neurotoxicity is the most important dose-limiting problem associated with cisplatin; peripheral neurotoxicity develops in approximately 50% of patients receiving cisplatin, but the onset of toxicity is delayed until a cumulative dose higher than 300 mg/m2 has been given. Whereas Oxaliplatin’s toxicity develops in about 15% of patients with prolonged treatment with oxaliplatin cumulative dose of 850 mg/m2, eventually causing impaired proprioception and neurosensory function. In contrast to cisplatin-induced neuropathy, oxaliplatin-induced neuropathy is reversible within 3-4 months of treatment discontinuation.
As for Carboplatin, compared to other platinum derivatives, neurotoxicity is less frequent (4 to 6%) and relatively mild. The risk of neurotoxicity is more dependent on the partnering agent.
Thalidomide dose as a single agent ranges from 100 to 1200 mg per day, peripheral neuropathy is not dose or duration dependant.
Though it’s a Thalidomide analog, the incidence of peripheral neuropathy with lenalidomide is very low and some researchers even see that this therapy does not even worsen peripheral neuropathy.
Peripheral neuropathy is a significant toxicity of bortezomib, the reported incidence of bortezomib induced neuropathy ranged between 30% and 64%. It’s given at a dose of 1.5 mg/m2 administered twice weekly and neurotoxicity has no correlation with cumulative dose or dose intensity of bortezomib. Dose reduction or discontinuation of treatment reverses or improves symptoms.
Ixabepilone, received at a dose of 40 mg/m2 IV every 3 weeks, causes peripheral sensory neuropathy in 20% of patients. Dose reduction or discontinuation of treatment is advised if neuropathy went severe. Ixabepilone-induced peripheral neuropathy is reversible and rapid.
Unfortunately, no successful treatment for established CIPN was discovered; recommendations on treatment of CIPN in cancer patients are usually based on studies concerning ‘benign’ neuropathic pain, such as painful diabetic neuropathy, post-herpetic neuralgia and trigeminal neuralgia. Most of the efforts are now directed towards prophylaxis against CIPN and relief of symptoms.
Treatment of radiation-induced neuropathies in general is symptomatic, others also suggest removing co-morbidity factors as controlling diabetes and high blood pressure and stopping alcohol abuse. The main act is prophylaxis; trying to keep nerve plexuses away from the target volume through optimal field arrangement and if inevitably irradiated, received doses shouldn’t go beyond the acceptable tolerance dose.
Treatment of post-operative pain involves a multimodal approach that includes injections (e.g. regional nerve blocks using lidocaine and/or corticosteroids), pharmacotherapy (e.g. opioids, anticonvulsants, antidepressants and local anaesthetics), physiotherapy, complementary and alternative therapies (e.g. hypnosis and cognitive behavioural therapy), surgery, and prevention.
It’s also important to not forget to pay attention to the patient’s nutritional status and the presence of co-morbidities that may aggravate peripheral neuropathy. Nutritional deficiencies should be supplemented and co-morbidities should be managed accordingly.