Neurophysiological, nerve imaging and other techniques to assess chemotherapy-induced peripheral neurotoxicity in the clinical and research settings

Abstract

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common dose-limiting side effect of several anticancer medications. CIPN may involve multiple areas of the peripheral nervous system from the autonomic and dorsal root ganglia (DRG) to the axon and any peripheral nerve fibre type. Large diameter sensory myelinated (Aβ) fibres are more frequently involved, but motor, small myelinated (Aδ), unmyelinated (C) or autonomic fibres may also be affected. Here, we review the current evidence on techniques for the CIPN assessment in the clinical and experimental settings. Nerve conduction studies (NCS) may be used at the subclinical and early CIPN stage, to assess the extent of large nerve fibre damage and to monitor long-term outcomes, with the sural or dorsal sural nerve as the most informative. The quantitative sensory neurological examination provides valuable data alongside NCS. Quantitative sensory testing and nerve excitability studies add information regarding pathophysiology. Nerve MRI and ultrasound may provide information on enlarged nerve, increased nerve signal intensity and DRG or spinal cord changes. Skin biopsy, corneal confocal microscopy, laser-evoked potentials, contact heat-related potentials and microneurography may reveal the extent of damage to small unmyelinated nerve fibres that go undetected by NCS. The information on the role of these latter techniques is preliminary. Hence, the use of multimodal testing is recommended as the optimal CIPN assessment strategy, employing objective NCS and other specialised techniques together with subjective patient-reported outcome measures.

Oxaliplatin‐ and docetaxel‐induced polyneuropathy: clinical and neurophysiological characteristics

“…53 For bedside testing, vibration detection threshold might be a useful screening tool, 54 which supports the use of vibration sense as a bedside test and early predictor of CIPN. 3,17,55 There was a poor agreement between abnormal thermal detection and mechanical pain thresholds, and more studies are needed to identify reliable bedside tests to assess small fiber function.…”

“…15,16 There is an increased awareness of the need for multimodal assessment tools to accurately diagnose and characterize CIPN. 4,17 No screening tools have been developed for detecting the presence or absence of CIPN. Despite the similarity between CIPN and other polyneuropathies, such as painful diabetic polyneuropathy, 18 the screening tools commonly used for diabetes, such as the grading system proposed by the Toronto Diabetic Neuropathy Expert group, 19 the Michigan Neuropathy Screening Instrument (MNSI), 20 and the Toronto Clinical Scoring System (TCSS), 21 are not used for diagnosing CIPN.…”

“…25,26 There is a need for a detailed assessment of large and small nerve fiber function as well as a quantification of motor function after chemotherapy. 17 We therefore conducted a deep-profile study of patients 5 years after receiving chemotherapy with docetaxel or oxaliplatin using a wide scale of assessment tools to determine the pattern of their neuropathy and neuropathic pain and the effect of quality of life and psychological functioning. The study is part of a 5-year follow-up of a prospective questionnaire study.…”

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

“…Only clinical assessment tools (not functional assessment tools) specifically designed for or validated in CIPN were included. Quantification of CIPN through neurophysiological means is not addressed but is reviewed in Argyriou et al Similarly, general toxicity or chemotherapy‐specific general toxicity measures were excluded.…”

Evidence of Altered Peripheral Nerve Function in a Rodent Model of Diet-Induced Prediabetes

“…In addition to standard electrophysiological measures, we utilized nerve excitability studies, which enable the indirect measurement of axonal ion-channel function and membrane potential [15]. Nerve excitability measures have proven sensitive to alterations in nerve function due to metabolic and toxic exposures [16,17] although they have not been extensively utilized in animal models. These measures demonstrate changes prior to nerve conduction abnormalities and thus represent a marker of early pathology [18,19].…”