The best magazine
Clinical Manifestations and Assessment
As the most frequently encountered neuropathic mechanisms target neurons or their axons (see Table 1 and Fig. 1), toxic, DIPNs, and CIPNs are mainly most often characterized by the development of a subacute or chronic, length-dependent, distal, symmetrical polyneuropathy with a predominant sensory involvement, with or without associated dysautonomia. This corresponds to the so-called 'dying back axonal degeneration' affecting distal segments of the peripheral nerves. Interestingly, most chemotherapeutic drugs poorly penetrate through the blood–brain barrier, but readily pass through the blood–nerve barrier, probably explaining the clinical observation of toxic damage preferentially affecting the sensory neurons of the dorsal root ganglia (DRG). These induced sensory neuronopathies are now more easily recognized by newly proposed diagnostic strategies. Chronic alcoholic neuropathy, vitamin-related neuropathies, and CIPNs (platin compounds, vinka alkaloids, taxanes, bortezomib, and thalidomide) are classical examples of substance-induced neuropathies, and have been recently extensively reviewed. CIPN is one of the main reasons for patients to prematurely terminate antineoplastic treatment. This is now well recognized, but as the number of long-term cancer survivors increases, new methods of rehabilitation are discussed to improve the patients' functions and quality of life. Other recently recognized DIPNs include those from long-term triazole antifungal therapies – ixabepilone for metastatic breast cancer, bendamustine for lymphomas, and stavudine in children receiving antiretroviral treatment. Less toxic and potentially superior alternatives are now reported for the management of nonsmall cell lung cancer and for the front-line treatment of advanced gastric or gastroesophageal adenocarcinoma.
(Enlarge Image)
Figure 1.
Neuronal targets of drug-induced peripheral neuropathy (numbers refer to Table 1).
More rarely, a nonlength-dependent or multifocal neuropathy may be encountered, either resembling chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or Lewis Sumner syndrome in DIPN associated with underlying inflammatory or dysimmune mechanisms. A nonlength-dependent small-fiber neuropathy may also be observed, such as in nitrofurantoin toxicity.
Assessment and grading of peripheral neuropathies remain subject to discussions, as most of the frequently used scales and grading systems rely on subjective evaluation either by the patient or the examiner. This is well illustrated in CIPN, where use of one of the classical grading systems, the National Cancer Institute Common Toxicity Criteria (NCI-CTC), tends to overestimate motor neuropathies compared to a composite scale designed to grade impairment in neuropathy patients [Total Neuropathy Score (TNS)], despite both grading systems having good inter and intra-observer reproducibility. The newly developed Chemotherapy-Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx) questionnaire acknowledge a considerable negative impact of neuropathy symptoms on daily activities in cancer patients treated with chemotherapy. Quantification or early detection is a persistent matter of debate, but new noninvasive tools for diagnosis are emerging, such as nerve excitability studies utilizing threshold tracking techniques, or laser Doppler flowmetry quantifying the small-fiber impairment by the reduced axon-reflex flare areas.
Source: ...