Antineoplastic agents exacerbating Charcot Marie Tooth disease: red flags to avoid permanent disability

Ibáñez-Juliá, María-José; Berzero, Giulia; Reyes-Botero, G; Maisonobe, Thierry; Lenglet, Timothée; Slim, Michel S.; Louis, Sarah; Balaguer, Aitana; Sanson, Marc; Guern, E. Le; Latour, Philippe; Ricard, Damien; Stojkovic, Tanya; Psimaras, Dimitri

doi:10.1080/0284186x.2017.1415462

Cited by 24 publications

(24 citation statements)

References 39 publications

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“…In addition, the NCVs measured between the sciatic notch and the lumbrical muscle of the foot was significantly reduced after acrylamide treatment in mutant animals compared to their wild type littermates. Similarly, an exacerbation of the phenotype has been observed in mildly affected patients carrying mutations in PMP22, SH3TC2, and MPZ undergoing chemotherapy, supporting the relevance of the model [43].…”

Section: Modelling Lrsam1mentioning

confidence: 58%

LRSAM1 and the RING domain: Charcot–Marie–Tooth disease and beyond

Palaima

Berciano

Peeters

et al. 2021

Orphanet J Rare Dis

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In the past decade, mutations in LRSAM1 were identified as the genetic cause of both dominant and recessive forms of axonal CMT type 2P (CMT2P). Despite demonstrating different inheritance patterns, dominant CMT2P is usually characterized by relatively mild, slowly progressive axonal neuropathy, mainly involving lower limbs, with age of onset between the second and fifth decades of life. Asymptomatic individuals were identified in several pedigrees exemplifying the strong phenotypic variability of these patients requiring serial clinical evaluation to establish correct diagnosis; in this respect, magnetic resonance imaging of lower-limb musculature showing fatty atrophy might be helpful in detecting subclinical gene mutation carriers. LRSAM1 is a universally expressed RING-type E3 ubiquitin protein ligase catalysing the final step in the ubiquitination cascade. Strikingly, TSG101 remains the only known ubiquitination target hampering our mechanistic understanding of the role of LRSAM1 in the cell. The recessive CMT mutations lead to complete loss of LRSAM1, contrary to the heterozygous dominant variants. These tightly cluster in the C-terminal RING domain highlighting its importance in governing the CMT disease. The domain is crucial for the ubiquitination function of LRSAM1 and CMT mutations disrupt its function, however it remains unknown how this leads to the peripheral neuropathy. Additionally, recent studies have linked LRSAM1 with other neurodegenerative diseases of peripheral and central nervous systems. In this review we share our experience with the challenging clinical diagnosis of CMT2P and summarize the mechanistic insights about the LRSAM1 dysfunction that might be helpful for the neurodegenerative field at large.

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Section: Modelling Lrsam1mentioning

confidence: 58%

LRSAM1 and the RING domain: Charcot–Marie–Tooth disease and beyond

Palaima

Berciano

Peeters

et al. 2021

Orphanet J Rare Dis

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“…A clinical challenge is undiagnosed cases of CMT, and seeking information about family history of CMT before initiating chemotherapy with vincristine could possibly prevent patients from severe neuropathy given that pediatric ALL often is diagnosed before the age of 10 and CMT after the age of 10 [51]. Pediatric and adult cancer patients are at risk of undiagnosed CMT [50]. Even small doses of vincristine that are normally not associated with neuropathy can cause exaggerated and irreversible neuropathy in these patients [50].…”

Section: Resultsmentioning

confidence: 99%

“…Pediatric and adult cancer patients are at risk of undiagnosed CMT [50]. Even small doses of vincristine that are normally not associated with neuropathy can cause exaggerated and irreversible neuropathy in these patients [50]. Another form of neuropathy presenting clinical problems is the autoimmune Guillain–Barré syndrome (GBS).…”

Section: Resultsmentioning

confidence: 99%

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Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review

Madsen

Due

Ejskjær

et al. 2019

Cancer Chemother Pharmacol

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Purpose Vincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy, possibly including both peripheral sensory and motor nerves, autonomic nervous functions, and the central nervous system. This dose-limiting side-effect can diminish quality of life and, furthermore, cause discontinuation of vincristine treatment. The present review elucidates the current knowledge regarding vincristine-induced neuropathy in hematologic malignancies, focusing on neuropathy assessment, clinical and molecular predictive markers, drug–drug interference, prevention, and treatment. Methods This review is conducted by a systematic search strategy for the identification of relevant literature in the PubMed and Embase databases. Results No clinical parameters displayed convincing potential as predictors of vincristine-induced neuropathy; however, preexisting neuropathy was consistently reported to be associated with an increased risk of neurotoxicity. In contrast, molecular markers, including polymorphisms in genes involved in the pharmacodynamics and pharmacokinetics of vincristine, displayed great potential as predictive markers of neuropathy incidence and severity. Furthermore, antifungal drugs, such as itraconazole and voriconazole, decrease the metabolism of vincristine and consequently lead to severe neuropathy when co-administered with vincristine, underscoring why fluconazole should be the antifungal drug of choice. Conclusion Reports from the 71 included studies clearly emphasize the lack of consistency in neuropathy assessment, grading systems, and reporting, making it difficult to interpret results between studies. Thus, truer clinical and molecular markers could emerge if the consistency of neuropathy detection and reporting increases by the use of conventional standardized neuropathy assessment tools and grading scales. Electronic supplementary material The online version of this article (10.1007/s00280-019-03884-5) contains supplementary material, which is available to authorized users.

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“…In addition, patients' characteristics, such as an older age, increased body mass index, race, and genetic background also influence PIPN risk . Comorbidities such as diabetes mellitus, Charcot–Marie–Tooth disease, alcoholism, liver diseases, and concurrent medications have also been suggested to predispose patients to drug‐induced peripheral neuropathies . However, many of these results have not been replicated or have contradictory results in the literature.…”

Section: Introductionmentioning

confidence: 99%

Concomitant Medications and Risk of Chemotherapy-Induced Peripheral Neuropathy

et al. 2018

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Background Peripheral neuropathy is the dose‐limiting toxicity of many oncology drugs, including paclitaxel. There is large interindividual variability in the neuropathy, and several risk factors have been proposed; however, many have not been replicated. Here we present a comprehensive study aimed at identifying treatment and physiopathology‐related paclitaxel‐induced neuropathy risk factors in a large cohort of well‐characterized patients. Patients and Methods Analyses included 503 patients with breast or ovarian cancer who received paclitaxel treatment. Paclitaxel dose modifications caused by the neuropathy were extracted from medical records and patients self‐reported neuropathy symptoms were collected. Multivariate logistic regression analyses were performed to identify concomitant medications and comorbidities associated with paclitaxel‐induced neuropathy. Results Older patients had higher neuropathy: for each increase of 1 year of age, the risk of dose modifications and grade 3 neuropathy increased 4% and 5%, respectively. Cardiovascular drugs increased the risk of paclitaxel dose reductions (odds ratio [OR], 2.51; p = .006), with a stronger association for beta‐adrenergic antagonists. The total number of concomitant medications also showed an association with dose modifications (OR, 1.25; p = .012 for each concomitant drug increase). A dose modification predictive model that included the new identified factors gave an area under the curve of 0.74 (p = 1.07 × 10−10). Preexisting nerve compression syndromes seemed to increase neuropathy risk. Conclusion Baseline characteristics of the patients, including age and concomitant medications, could be used to identify individuals at high risk of neuropathy, personalizing chemotherapy treatment and reducing the risk of severe neuropathy. Implications for Practice Peripheral neuropathy is a common adverse effect of many cancer drugs, including chemotherapeutics, targeted therapies, and immune checkpoint inhibitors. About 40% of survivors of cancer have functional deficits caused by this toxicity, some of them irreversible. Currently, there are no effective treatments to prevent or treat this neuropathy. This study, performed in a large cohort of well‐characterized patients homogenously treated with paclitaxel, identified concomitant medications, comorbidities, and demographic factors associated with peripheral neuropathy. These factors could serve to identify patients at high risk of severe neuropathy for whom alternative non‐neurotoxic alternatives may be considered.

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Antineoplastic agents exacerbating Charcot Marie Tooth disease: red flags to avoid permanent disability

Abstract: A brief checklist to disclose long-standing signs of peripheral neuropathy could be helpful to detect patients with undiagnosed hereditary neuropathies who could be at risk of developing severe irreversible neurotoxicity following the administration of neurotoxic agents.

Cited by 24 publications

References 39 publications

LRSAM1 and the RING domain: Charcot–Marie–Tooth disease and beyond

LRSAM1 and the RING domain: Charcot–Marie–Tooth disease and beyond

Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review

Concomitant Medications and Risk of Chemotherapy-Induced Peripheral Neuropathy

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