Balance impairments and neuromuscular changes in breast cancer patients with chemotherapy-induced peripheral neuropathy

Kneis, Sarah; Wehrle, Anja; Freyler, Kathrin; Lehmann, K.; Rudolphi, Britta; Hildenbrand, Bernd; Bartsch, Hans Helge; Bertz, Hartmut; Gollhofer, Albert; Ritzmann, Ramona

doi:10.1016/j.clinph.2015.07.022

Cited by 83 publications

(63 citation statements)

References 63 publications

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“…the sensory ataxia with postural instability and clumsiness (Bennett et al, 2012; Kneis et al, 2015) that can be induced by chemotherapy and continue long after its removal, we developed a rodent model of chronic OX treatment. This model reproduced the absence of neuropathy observed in some OX patients, but it revealed chronic dysfunction in proprioceptive signaling (Bullinger et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

Vincent

Wieczerzak

Gabriel

et al. 2016

Neurobiology of Disease

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Persistent neurotoxic side effects of Oxaliplatin (OX) chemotherapy, including sensory ataxia, limit the efficacy of treatment and significantly diminish patient quality of life. The common explanation for neurotoxicity is neuropathy, however the degree of neuropathy varies greatly among patients and appears insufficient in some cases to fully account for disability. We recently identified an additional mechanism that might contribute to sensory ataxia following OX treatment. In the present study, we tested whether that mechanism, selective modification of sensory signaling by muscle proprioceptors might result in behavioral deficits in rats. OX was administered once per week for seven weeks (cumulative dose i.p. 70 mg/kg) to adult female Wistar rats. Throughout and for three weeks following treatment, behavioral analysis was performed daily on OX and sham control rats. Compared to controls, OX rats demonstrated errors in placing their hind feet securely and/or correctly during a horizontal ladder rung task. These behavioral deficits occurred together with modification of proprioceptor signaling that eliminated sensory encoding of static muscle position while having little effect on encoding of dynamic changes in muscle length. Selective inability to sustain repetitive firing in response to static muscle stretch led us to hypothesize that OX treatment impairs specific ionic currents, possibly the persistent inward Na currents (NaPIC) that are known to support repetitive firing during static stimulation in several neuron types, including the class of large diameter dorsal root ganglion cells that includes muscle proprioceptors. We tested this hypothesis by determining whether the chronic effects of OX on the firing behavior of muscle proprioceptors in vivo were mimicked by acute injection of NaPIC antagonists. Both riluzole and phenytoin, each having multiple drug actions but having only antagonist action on NaPIC in common, reproduced selective modification of proprioceptor signaling observed in OX rats. Taken together, these findings lead us to propose that OX chemotherapy contributes to movement disability by modifying sensory encoding, possibly via a chronic neurotoxic effect on NaPIC in the sensory terminals of muscle proprioceptors.

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Section: Introductionmentioning

confidence: 99%

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

Vincent

Wieczerzak

Gabriel

et al. 2016

Neurobiology of Disease

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“…The feasibility of collecting objective balance data in the oncology clinic has been demonstrated, 4,5 and several groups have reported balance impairments that are demonstrated in cancer patients in different stages of treatment or survivorship. 2,4,[6][7][8][9][10][11] However, much is still unknown about how common neurotoxic adverse effects of treatment associate with balance impairments.…”

Section: Introductionmentioning

confidence: 99%

Impaired Postural Control and Altered Sensory Organization During Quiet Stance Following Neurotoxic Chemotherapy: A Preliminary Study

et al. 2019

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Individuals diagnosed with chemotherapy-induced peripheral neuropathy (CIPN) demonstrate impaired balance and carry an increased risk of falling. However, prior investigations of postural instability have only compared these individuals against healthy controls, limiting the understanding of impairments associated with CIPN. Therefore, the purpose of this study was to better isolate postural control impairments that are associated with CIPN. Twenty cancer survivors previously diagnosed with breast or colorectal cancer participated. Participants were separated into 3 groups: no prior chemotherapy exposure (CON, n = 6), and recent treatment with taxane-or oxaliplatin-based chemotherapy with no/mild symptoms of CIPN (−CIPN, n = 8) or moderate/severe symptoms of CIPN (+CIPN, n = 6). Postural control was assessed by measuring center of pressure during standing balance conditions that systematically interfered with somatosensory, visual, and/or vestibular information. The presence of CIPN sensory symptoms was associated with impaired postural control, particularly during eyes-closed balance conditions (P < .05). Additionally, medial-lateral postural instability was more pronounced in the +CIPN group compared with the −CIPN group and CON participants (P < .05). Greater postural instability during eyes-closed balance in individuals with CIPN is consistent with impaired peripheral sensation. Balance impairments in cancer survivors with CIPN demonstrate the unique challenges in this population and motivate the need for targeted efforts to mitigate postural control deficits that have previously been associated with fall risk.

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“…Therefore, although evidence supports that unmyelinated C and myelinated Aδ fibers may experience a neurotoxic effect due to chemotherapy, and possibly even type Ia afferent fibers part of reflex arcs, the primary fibers that experience the neurotoxic effect of thermotherapy may not be prime gait mediators, which may explain why there were no significant differences found in EFFECTS OF CIPN ON GAIT AND FALL RISK 89 spatial and temporal gait parameters other than velocity between those with CIPN and their healthy and morphologically matched controls (Kneis et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…In cancer patients with CIPN, impairments may manifest as gait or balance disorders, which may be linked to higher rates of falling, limiting activities of daily living. However, the exact nature in which CIPN affects the spatiotemporal mechanism of gait remains largely unknown (Kneis et al, 2015).…”

Section: Effects Of Cipn On Gait and Fall Risk 92mentioning

confidence: 99%

Effects of Chemotherapy-Induced-Peripheral-Neuropathy on Spatiotemporal Gait Parameters and Fall Risk in Cancer Patients After the Completion of Chemotherapy Drug Treatment

Marshall

Zipp²,

Battaglia³

et al. 2016

Archives of Physical Medicine and Rehabilitation

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Balance impairments and neuromuscular changes in breast cancer patients with chemotherapy-induced peripheral neuropathy

Cited by 83 publications

References 63 publications

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

A novel path to chronic proprioceptive disability with oxaliplatin: Distortion of sensory encoding

Impaired Postural Control and Altered Sensory Organization During Quiet Stance Following Neurotoxic Chemotherapy: A Preliminary Study

Effects of Chemotherapy-Induced-Peripheral-Neuropathy on Spatiotemporal Gait Parameters and Fall Risk in Cancer Patients After the Completion of Chemotherapy Drug Treatment

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