Guillain-Barré syndrome in a patient with metastatic colon cancer receiving oxaliplatin-based chemotherapy

Abstract

We report Guillain-Barre syndrome (GBS), developed in a patient with metastatic colon cancer, receiving oxaliplatin-based chemotherapy. The 53-year-old patient was treated with first-line chemotherapy consisting of oxaliplatin 45 mg/m2, 5-fluorouracil 450 mg/m2 and folinic acid 200 mg/m2, all given on the same day in a weekly schedule. After 13 weeks of treatment and a cumulative oxaliplatin dose of 585 mg/m2, the patient developed unsteadiness of gait, dysphagia, and weakness of both the upper and lower limbs, as well as impairment of all sensory modalities. Clinical examination, computed tomography and magnetic resonance imaging scans of the brain, blood tests, nerve conduction studies, and cerebrospinal fluid analysis confirmed the diagnosis of GBS. Intravenous immunoglobulin G was administered for 5 days and the patient recovered fully. Oxaliplatin can cause acute and delayed neurotoxicity, but this is the first report of GBS in a patient receiving oxaliplatin-based chemotherapy. Elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, induced by oxaliplatin, may represent the relevant causal links involved in the cascade of events which have led to the immune-mediated demyelination in the peripheral nervous system in this patient.

Platinum‐induced peripheral neurotoxicity: From pathogenesis to treatment

“…Therefore, when motor and autonomic symptoms are predominant and/or there is an absence of sensory involvement, an alternative diagnosis should be considered. As an example, platinum‐based compounds have been rarely associated with acute inflammatory demyelinating polyradiculoneuritis in patients with solid tumor, which appears to respond well to standard immunotherapy. Additionally, it is important to be aware that treatment with more than one neurotoxic agent may increase the likelihood of peripheral neuropathy, which may be associated with involvement of the autonomic system (especially parasympathetic heart innervation) …”

Delayed Oxaliplatin-Induced Sensorimotor Polyneuropathy

“…All platinum compounds typically produce 'coasting' where neuropathy progresses for weeks to several months after drug treatment ends, and our findings may be correlatedwiththisphenomenon.However,sincethemotor symptomssharesimilaritieswiththoseobservedintheacute neurotoxicity of oxaliplatin, it could also be speculated that animmuno-mediatedNa + channeldysfunctionplaysarolein thepathogenesisofdelayedneuropathy.Notably,allpatients developedacutesymptomsofcoldhypersensitivity,and2pa-tients muscle discomfort. In agreement with this hypothesis, Christodoulou et al [13] reported the occurrence of Guillan-Barrèsyndromeinapatientwithmetastaticcoloncancer receivingoxaliplatin-basedchemotherapy.Theauthorsargue that elevation of pro-inflammatory cytokines such as tumor necrosisfactor-alphaandinterleukin-6,inducedbyoxaliplatin mayrepresenttherelevantcausallinkinvolvedinthecascade ofeventswhichhaveledtotheimmune-mediateddemyelinationinthispatient.Interestingly,Noronhaetal. [14]recently reported the case of a woman with metastatic carcinoma of theileocecalregion,whoreceivedFOLFOXand,afterpartial remission with minimal side-effects, developed a mild selflimitedepisodeofimmune-mediatedhemolyticanemia.Our preliminary observations indicate that delayed sensorimotor polyneuropathy is a complication which must be considered forpatientsreceivingadjuvantoxaliplatin-containingchemotherapy.…”

A case of Guillain-Barre syndrome in a patient with small cell lung cancer treated with chemotherapy

“…[16,17] Okzaliplatin, vinkristin, L-asparginaz, daunorubisin gibi bazı kemoterapi ajanları GBS gelişimi ile ilişkili bulunmuştur. [8][9][10] Tümör hücrelerinden eksprese edilen onko-nöral antijenlerin, anti-onko-nöral veya anti-myelin antikorları uyararak nöron hasarını başlattığı düşünül-mektedir. Ayrıca platin bazlı kemoterapinin TNFalfa ve IL-6 gibi sitokinleri artırdığı ve nöronlarda enflamatuvar hasarı tetiklediği de gösterilmiştir.…”

“…[6] Literatürde, kanserle ve antikanser tedaviyle iliş-kili GBS olguları bildirilmiştir. [7][8][9][10] Burada kanser ve febril nötropeni ile ilişkili olabilecek nadir bir durum olan GBS deneyimimizi sunmak istedik.…”