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ABSTRACT: The mechanisms of lead neuropathy remain unexplained. A 48-year-old painter presented after undertaking a 3-week project of paint removal without the use of a protective mask. Two weeks later, he developed fasciculations, weakness, and muscle wasting. Nerve conduction studies demonstrated a motor neuropathy. A high serum lead level was identified, leading to a diagnosis of acute lead neuropathy.
To investigate the pathophysiology, nerve excitability studies were undertaken acutely and in convalescence. Studies were undertaken at baseline and after the induction of limb ischemia.
Prominent abnormalities of excitability were noted, including a rightward shift of stimulus-response curves, reduction in depolarizing threshold electrotonus, and increased refractoriness. These changes became more severe with limb ischemia, and there was abolition of the superexcitable period and increased refractoriness.
We identified prominent changes in nerve excitability in lead neuropathy. The results suggest that there is impairment of axonal energy-dependent processes in lead neuropathy. Muscle Nerve, 2012.
Muscle & Nerve 12/2012; 46(6):954-6. · 2.37 Impact Factor
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ABSTRACT: OBJECTIVE: To elucidate longitudinal changes in axonal function in amyotrophic lateral sclerosis (ALS) patients, and to relate such changes with motor unit loss and functional impairment. METHODS: 37 ALS patients (age, 53.7±1.7years; 22 males) were studied using axonal excitability techniques at baseline and 12weeks follow-up. RESULTS: Longitudinal measurements across excitability parameters suggested increasing K(+) channel dysfunction, with further increases in depolarising threshold electrotonus (90-100ms, baseline, 46.8±1.0%; follow-up, 48.7±0.8%; P=0.02) and superexcitability (baseline, -24.0±1.2%; 12weeks, -26.0±1.2%; P=0.04). Patients with preserved compound muscle action potential (CMAP) amplitude at follow-up developed more severe changes in axonal excitability than those in whom CMAP decreased from baseline, suggesting that the most pronounced disease effects were on motor axons immediately prior to axonal loss in ALS patients. Fine motor decline was associated with more severe changes in axonal excitability, suggesting that functional impairment was related to axonal dysfunction. CONCLUSIONS: Longitudinal changes in axonal excitability in ALS patients suggest increasing K(+) channel dysfunction in motor axons. SIGNIFICANCE: Axonal excitability studies enable investigation of longitudinal changes in axonal ion channel dysfunction, and thereby the processes that potentially contribute to axonal degeneration in ALS.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 08/2012; · 3.12 Impact Factor
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ABSTRACT: To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA(1c) levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0-1 [n = 35]), grade 1 (TNS 2-8 [n = 42]), and grade 2/3 (TNS 9-24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA(1c) level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction.
Diabetes 04/2012; 61(6):1592-8. · 8.29 Impact Factor
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ABSTRACT: Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment, producing initial acute neurotoxicity and chronic neuropathy with increasing exposure. The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin has highlighted the need for valid and reliable assessment of peripheral neuropathy.
The objective of this paper was to explore neuropathic symptoms in oxaliplatin-treated patients as assessed using different methods.
Consecutive symptomatic patients reporting peripheral neuropathy after oxaliplatin chemotherapy for colorectal cancer were interviewed using a semi-structured clinical interview. Neurotoxicity was also assessed using the National Cancer Institute Common Toxicity Criteria scale (clinician-rated), patient 'self-report' questionnaires (PNQ), nerve conduction and clinical assessment.
Twenty patients were assessed, 12.6 ± 2.8 months after treatment cessation (mean cumulative oxaliplatin dose, 789 mg/m(2)). In 40% of patients, neurotoxicity necessitated early cessation of treatment. Only 10% of patients were designated by clinicians with severe neurotoxicity, whilst, in contrast, patient interviews and self-report questionnaires described significant physical limitations due to neuropathic symptoms in 60% of patients. The majority (85%) of patients had objective evidence of sensory neuropathy with nerve conduction studies. Reports from clinical interviews were strongly correlated with patient self-assessment (Pearson coefficient = 0.790, p < 0.0005).
Given the discrepancies in symptom prevalence highlighted by these findings, the monitoring of oxaliplatin-induced neurotoxicity would benefit from more informative clinical assessment, with inclusion of patient-reported outcome measures. Such an approach would be beneficial in a clinical trial setting to monitor the efficacy of interventions and in prospective studies of survivorship to determine the true burden of peripheral neuropathy in oxaliplatin-treated patients.
Supportive Care in Cancer 03/2012; 20(11):2959-67. · 2.09 Impact Factor
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Neurology 01/2012; 78(2):152. · 8.31 Impact Factor
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ABSTRACT: Chemotherapy-induced neurotoxicity is a serious consequence of cancer treatment, which occurs with some of the most commonly used chemotherapies(1,2). 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 prognosis(3). 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 objectivity(4). 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 neurotoxicity(4-6). 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 axons(7-9). Nerve excitability techniques have been established as a tool to examine the development and severity of chemotherapy-induced neurotoxicity(10-13). 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 axons(10-13). Importantly, patients who demonstrated changes in excitability in early treatment were subsequently more likely to develop moderate to severe neurotoxicity(11). However, across treatment, striking longitudinal changes were identified only in sensory axons which were able to predict clinical neurological outcome in 80% of patients(10). 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 treatment(10). 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.
Journal of Visualized Experiments 01/2012;
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ABSTRACT: Spinal muscular atrophy is distinct among neurodegenerative conditions of the motor neuron, with onset in developing and maturing patients. Furthermore, the rate of degeneration appears to slow over time, at least in the milder forms. To investigate disease pathophysiology and potential adaptations, the present study utilized axonal excitability studies to provide insights into axonal biophysical properties and explored correlation with clinical severity. Multiple excitability indices (stimulus-response curve, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle) were investigated in 25 genetically characterized adolescent and adult patients with spinal muscular atrophy, stimulating the median motor nerve at the wrist. Results were compared with 50 age-matched controls. The Medical Research Council sum score and Spinal Muscular Atrophy Functional Rating Scale were used to define the strength and motor functional status of patients with spinal muscular atrophy. In patients with spinal muscular atrophy, there were reductions in compound muscle action potential amplitude (P < 0.0005) associated with reduction in stimulus response slope (P < 0.0005), confirming significant axonal loss. In the patients with mild or ambulatory spinal muscular atrophy, there was reduction of peak amplitude without alteration in axonal excitability; in contrast, in the non-ambulatory or severe spinal muscular atrophy cohort prominent changes in axonal function were apparent. Specifically, there were steep changes in the early phase of hyperpolarization in threshold electrotonus (P < 0.0005) that correlated with clinical severity. Additionally, there were greater changes in depolarizing threshold electrotonus (P < 0.0005) and prolongation of the strength-duration time constant (P = 0.001). Mathematical modelling of the excitability changes obtained in patients with severe spinal muscular atrophy supported a mixed pathology comprising features of axonal degeneration and regeneration. The present study has provided novel insight into the pathophysiology of spinal muscular atrophy, with identification of functional abnormalities involving axonal K(+) and Na(+) conductances and alterations in passive membrane properties, the latter linked to the process of neurodegeneration.
Brain 09/2011; 134(Pt 11):3185-97. · 9.46 Impact Factor
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ABSTRACT: Weakness and fatigue are commonly encountered symptoms in neurological disorders and significantly impair quality of life. In the case of motor axons, conduction block contributes to weakness and fatigue and may be associated with aberrant nerve activity including fasciculations and cramp. These symptoms result from dysfunction of the constituent channels and pumps of the axonal membrane. In critically conducting axons, impulse conduction can be impaired by the effects of activity or by other mechanisms that produce a significant shift in membrane potential. Conduction failure may be accentuated or relieved by maneuvers that manipulate the time course of the driving current, including the administration of agents that interfere with Na(+) channel function. In patients with inflammatory neuropathies, normal activity may be sufficient to precipitate conduction failure at sites of impaired function in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). From a clinical perspective, these features are not assessed adequately by conventional neurophysiological techniques. As weakness and fatigue may only develop following activity or exertion, it is useful to assess the effects of impulse trains to determine the extent of conduction failure and the resulting symptoms in neurological patients. These techniques and the physiological mechanisms underlying the development of activity-dependent hyperpolarization will be critically appraised in this review, with a focus on demyelinating neuropathies, MMN and the neurodegenerative disease, and amyotrophic lateral sclerosis (ALS).
Journal of the Peripheral Nervous System 09/2011; 16(3):159-68. · 2.80 Impact Factor
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ABSTRACT: The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays during an acute attack. If administered early, intravenous haemin may prevent progression of neuropathy. While the pathophysiology of AIP neuropathy remains unclear, axonal dysfunction appears intrinsically linked to the effects of neural energy deficits acquired through haem deficiency coupled to the neurotoxic effects of porphyrin precursors. The present review will provide an overview of AIP neuropathy, including discussion of recent advances in understanding developed through neurophysiological approaches that have further delineated the pathophysiology of axonal degeneration.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 08/2011; 122(12):2336-44. · 3.12 Impact Factor
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ABSTRACT: To investigate the immediate and longitudinal mechanisms of action of intravenous immunoglobulin (IVIg) on axonal function in chronic inflammatory demyelinating polyneuropathy (CIDP).
Prospective single-center study.
Hospitals and outpatient clinics.
Clinical and functional assessment, nerve conduction studies, and 526 motor excitability studies were undertaken in 27 patients, matched before and immediately after infusion and followed up longitudinally.
Axonal excitability variables were measured before and immediately after infusion and compared with matched studies and findings in healthy controls.
Immediately after infusion, patients demonstrated decreased threshold, with significant reduction in strength-duration time constant (P = .003), reduction in accommodation to depolarization (P = .04), and reduced threshold change during hyperpolarization (P = .003), accompanied by significant decreases in superexcitability (P = .03) and subexcitability (P = .02). In contrast, changes were absent in disease controls, confirming a specific IVIg action in CIDP patients. Longitudinally, changes correlated with clinical improvement (mean [SE] increase in the Medical Research Council sum score, 2.7 [0.7]; P = .005). Increased compound muscle action potential amplitude was associated with reduction in terminal latency (correlation coefficient, -0.65; P = .02). In addition, these changes translated into improvement in functional assessment with the adjusted Inflammatory Neuropathy Cause and Treatment score, which demonstrated a significant correlation with nerve excitability variables longitudinally (P = .01).
Findings from the present series establish a modulatory effect of IVIg on axonal function in CIDP patients, suggesting that IVIg stabilizes axonal membrane potential and promotes axonal recovery.
Archives of neurology 07/2011; 68(7):862-9. · 6.31 Impact Factor
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Journal of Clinical Oncology 06/2011; 29(18):e553-4; author reply e555-6. · 18.37 Impact Factor
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ABSTRACT: Paclitaxel is used in the adjuvant treatment of breast cancer. It induces disabling and potentially long-lasting sensory neuropathy. This study systematically and prospectively investigated sensory function, using clinical grading scales, quantitative sensory testing, and neurophysiological and nerve excitability studies in 28 patients with early-stage breast cancer. After administration of 529 ± 41 mg/m(2) paclitaxel, 71% of patients developed neuropathic symptoms by 6 weeks of treatment. Early and progressive increases in stimulus threshold (P < 0.05) and reduction in sensory amplitudes from 47.0 ± 3.3 μV to 42.4 ± 3.4 μV (P < 0.05) occurred by 4 weeks, with a further reduction by final treatment (33.7 ± 3.0 μV, P < 0.001). The majority of patients (63%) did not experience recovery of neuropathic symptoms at follow-up. Axonal disruption did not relate to membrane conductance dysfunction. We found that paclitaxel produces early sensory dysfunction and leads to persistent neuropathy. Importantly, significant axonal dysfunction within the first month of treatment predated symptom onset, suggesting a window for neuroprotective therapies.
Muscle & Nerve 03/2011; 43(3):367-74. · 2.37 Impact Factor
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Cancer Chemotherapy and Pharmacology 02/2011; 67(5):1189-90; author reply 1191-2. · 2.83 Impact Factor
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ABSTRACT: To assess whether there are differences in nerve excitability properties between proximal and distal stimulation sites in the ulnar nerve in healthy controls, which may provide information on whether alteration in ion channel function predisposes to the development of ulnar neuropathy at the elbow.
Nerve excitability studies were undertaken in 11 healthy controls. Studies were undertaken with stimulation of the ulnar nerve at the elbow and wrist. Recordings were obtained from abductor digiti minimi in both sets of studies.
Recordings obtained following stimulation of the nerve at the elbow demonstrated significant differences to those obtained following stimulation of the nerve at the wrist. Specifically, there was a left shift in stimulus-response curves at the elbow compared to the wrist, with prolonged strength-duration time constant, and reduced rheobase (P<0.05). These changes were accompanied by increased refractoriness and reductions in superexcitability and late subexcitability (P<0.05).
The present findings may suggest relative depolarization of ulnar nerve axons at the elbow.
These changes may reflect regional differences in axonal Na(+)/K(+) pump function and thereby predispose the ulnar nerve to conduction failure and axonal degeneration when exposed to trauma.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 01/2011; 122(1):194-8. · 3.12 Impact Factor
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ABSTRACT: Oxaliplatin, a platinum-based chemotherapy utilised in the treatment of colorectal cancer, produces two forms of neurotoxicity--acute sensorimotor neuropathic symptoms and a dose-limiting chronic sensory neuropathy. Given that a Na(+) channelopathy has been proposed as the mechanism underlying acute oxaliplatin-induced neuropathy, the present study aimed to determine specific mechanisms of Na(+) channel dysfunction.
Specifically the function of transient and persistent Na(+) currents were followed during treatment and were investigated in relation to oxaliplatin dose level. Eighteen patients were assessed before and after a single oxaliplatin infusion with motor and sensory axonal excitability studies performed on the median nerve at the wrist. While refractoriness (associated with Na(+) channel inactivation) was significantly altered post-oxaliplatin infusion in both motor (Pre: 31.7±6.4%; Post: 68.8±14.5%; P≤.001) and sensory axons (Pre: 31.4±5.4%; Post: 21.4±5.5%; P<.05), strength-duration time constant (marker of persistent Na(+) conductances) was not significantly altered post-infusion (Motor Pre: 0.395±0.01 ms; Post: 0.394±0.02 ms; NS; Sensory Pre:0.544±0.03 ms; Post: 0.535±0.05 ms; NS). However, changes in strength-duration time constant were significantly correlated with changes in refractoriness in motor and sensory axons (Motor correlation coefficient = -.65; P<.05; Sensory correlation coefficient = .67; P<.05).
It is concluded that the predominant effect of acute oxaliplatin exposure in human motor and sensory axons is mediated through changes in transient rather than persistent Na(+) conductances. These findings are likely to have implications for the design and trial of neuroprotective strategies.
PLoS ONE 01/2011; 6(4):e18469. · 4.09 Impact Factor
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ABSTRACT: Oxaliplatin-induced neuropathy is a significant and dose-limiting toxicity that adversely affects quality of life. However, the long-term neurological sequelae have not been adequately described. The present study aimed to describe the natural history of oxaliplatin-induced neuropathy, using subjective and objective assessments.
From a population of 108 oxaliplatin-treated patients referred for neurological assessment in 2002-2008, 52.2% of the surviving patient cohort (n = 24) was available for follow-up at a median of 25 months post-oxaliplatin. Patients underwent a protocol that incorporated clinical assessment scales, patient questionnaires, standard electrodiagnostic assessments, and novel nerve excitability studies to precisely assess nerve function.
At follow-up, 79.2% of patients reported residual neuropathic symptoms, with distal loss of pin-prick sensibility in 58.3% of patients and loss of vibration sensibility in 83.3% of patients. Symptom severity scores were significantly correlated with cumulative dose. There was no recovery of sensory action potential amplitudes in upper and lower limbs, consistent with persistent axonal sensory neuropathy. Sensory excitability parameters had not returned to baseline levels, suggesting persisting abnormalities in nerve function. The extent of excitability abnormalities during treatment was significantly correlated with clinical outcomes at follow-up.
These findings establish the persistence of subjective and objective deficits in oxaliplatin-treated patients post-oxaliplatin, suggesting that sensory neuropathy is a long-term outcome, thereby challenging the literature on the reversibility of oxaliplatin-induced neuropathy.
The Oncologist 01/2011; 16(5):708-16. · 3.91 Impact Factor
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ABSTRACT: Oxaliplatin is first-line chemotherapy for colorectal cancer, but produces dose-limiting neurotoxicity. Acute neurotoxicity following infusion produces symptoms including cold-triggered fasciculations and cramps, with subsequent chronic neuropathy developing at higher cumulative doses. Axonal excitability studies were undertaken in 15 oxaliplatin-treated patients before and immediately after oxaliplatin infusion to determine whether the mechanisms underlying acute neurotoxicity altered resting membrane potential or Na(+)/K(+) pump function. Excitability properties were assessed before and after maximal voluntary contraction (MVC) of the abductor pollicis brevis. Following oxaliplatin infusion, abnormalities developed in the recovery cycle with refractoriness markedly increased. Following activity, changes developed consistent with axonal hyperpolarization, with proportional changes pre- and post-oxaliplatin in normalized threshold. However, recovery cycle parameters following activity were significantly and disproportionally enhanced post-oxaliplatin, with partial normalization of the recovery cycle curve post-activity. Patients with the most abnormal change in the recovery cycle after infusion demonstrated the greatest changes post-contraction. Prominent abnormalities developed in Na(+) channel-associated parameters in response to natural activity, without significant alteration in axonal membrane potential or Na(+)/K(+) pump function. Findings from the present series suggest that oxaliplatin affects nerve excitability through voltage-dependent mechanisms, with specific effects mediated through axonal Na(+) channel inactivation.
Experimental Neurology 10/2010; 227(1):120-7. · 4.70 Impact Factor
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ABSTRACT: The pathophysiology of stroke-like episodes in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) remains unresolved. Possible mechanisms include mitochondrial angiopathy, cytopathy, or both, collectively resulting in cellular energy depletion. To clarify disease mechanisms, axonal excitability properties were investigated in a 10-year-old child with MELAS. Serial assessments during a stroke-like episode revealed reversible depolarization of the axonal membrane consistent with disruption of energy-dependent processes. Axonal parameters correlated with the clinical assessment of central dysfunction and biochemical measures of acidosis. Novel axonal excitability techniques have established acute, reversible ischemic-like depolarization that may serve as a surrogate marker of central events that develop during stroke-like episodes in MELAS.
PEDIATRICS 09/2010; 126(3):e734-9. · 4.47 Impact Factor
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ABSTRACT: Chemotherapy-induced neurotoxicity is a common and dose-limiting side effect of many cancer treatments. While other dose-limiting
toxicities such as myelosupression and hypersensitivity reactions are largely amenable to treatment, chemotherapy-induced
neurotoxicity remains a significant problem, with limited treatment options and no standardized diagnostic or management criteria.
Receiving a full course of chemotherapy on schedule is a critical factor that determines patient survival. Neurotoxicity may
necessitate changes to dosage level, scheduling or intensity, and thereby interfere with the ability to complete a full treatment
regimen, even if therapy is proving effective.
With the majority of chemotherapies, the pathophysiological mechanisms of neurotoxicity remain unknown (Hausheer et al. 2006).
Neurotoxicity may occur as a consequence of treatment with platinum agents (cisplatin, carboplatin, oxaliplatin), taxanes
(paclitaxel, docetaxel) and vinca alkaloids (vincristine). Other therapies such as suramin, thalidomide, and bortezomib can
also produce significant neurotoxicity (Quasthoff and Hartung 2002; Hausheer et al. 2006). Previous or coincident administration
of neurotoxic chemotherapy or preexisting neuropathy may serve to accelerate the severity of symptoms (Chaudhry et al. 2003).
While neuropathy may be regarded as an acceptable outcome if disease progression has been arrested, neurotoxicity becomes
more problematic in the setting of adjuvant therapy.
12/2009: pages 99-119;
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ABSTRACT: Lhermitte's phenomenon, characterized by 'electric-shock' sensations precipitated by neck flexion, may develop during oxaliplatin treatment. Limited cases have been described previously and the pathophysiology underlying Lhermitte's phenomenon in oxaliplatin-treated patients has not been established.
Patients who developed Lhermitte's phenomenon during oxaliplatin therapy were investigated by neurological examination, neurotoxicity grading and conventional nerve conduction studies (NCS). Structural (magnetic resonance imaging) and functional (somatosensory evoked potentials) spinal assessment was also undertaken. Sensory nerve excitability recordings were performed longitudinally across treatment to investigate ion channel function.
Five oxaliplatin-treated patients reported Lhermitte's phenomenon, with a mean cumulative dose of 861 +/- 84 mg/m(2) oxaliplatin (range 574-1,100 mg/m(2)). NCS revealed severe sensory neuropathy in all patients. There was no evidence of structural or functional spinal cord damage. Nerve excitability studies revealed progressive alterations in sensory excitability throughout treatment, consistent with oxaliplatin-induced nerve dysfunction. In patients with Lhermitte's phenomenon, refractoriness was reduced to -14.4% (confidence interval, CI: -20.5 to -8.4%) by late treatment, a significantly greater reduction than in oxaliplatin-treated patients who did not develop Lhermitte's phenomenon (-2.7%; CI: -7.6 to 2.2; p = 0.013).
Lhermitte's phenomenon represents a severe presentation of oxaliplatin-induced neurotoxicity, associated with generalized nerve dysfunction in the absence of structural spinal abnormalities.
Oncology 12/2009; 77(6):342-8. · 2.27 Impact Factor
