Irinotecan-Induced Dysarthria

Abstract

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria.

Temporary Dysarthria Induced by Irinotecan-Case Report of This Rare Adverse Event

“…Furthermore, in this case the event was fully reversible and does not justify the discontinuation of the drug [15]. The duration of the event may vary between 15 min [16] and 24 h [17], but in most reported cases there was spontaneous resolution of the symptom after a few hours [11,14].…”

“…Only Gomez et al [9] reported a case of a patient who presented dysarthria associated to ataxia and tremors with complete resolution of the symptoms after administering atropine [9]. In this case dysarthria was not an isolated symptom, and the dose used was relatively lower to those administered in other case reports (80 mg/m²-350 mg/m²) [9,[14][15].…”

“…One would see higher frequency of dysarthria in these individuals which does not occur [14]. Another possibility outlined in the literature is the overstimulation of the hypoglossal nerve by accumulation of acetylcholine; however, this hypothesis is challenged by the concept of atropine preventing systemic cholinergic events but, in most cases, often does not prevent dysarthria [14,15]. Only Gomez et al [9] reported a case of a patient who presented dysarthria associated to ataxia and tremors with complete resolution of the symptoms after administering atropine [9].…”

“…MRI is commonly performed but rarely yields additional information. The measures described in the literature to alleviate this symptomatology are shown in Table 1 [8,9,11,[14][15][16][17][18][19][20].…”

FOLFIRINOX-induced reversible dysarthria: A case report and review of previous cases

“…Therefore, the unexpectedly high incidence of dysarthria appears to be a characteristic adverse effect of FOLFIRINOX that extends beyond ethnicity. Conversely, it is known that irinotecan directly causes dysarthria, although only 10 cases have been reported in the literature (2,3,(6)(7)(8)(9)(10)(11)(12)(13). Although irinotecan exerts its antitumor activity after being metabolized to SN-38 in vivo, dysarthria is apparently caused by the parent compound irinotecan binding to the active site of Table I.…”