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The Natural History of Vincristine-Induced Laryngeal Paralysis in Children

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The Natural History of Vincristine-Induced Laryngeal Paralysis in Children ORIGINAL ARTICLE The Natural History of Vincristine-Induced Laryngeal Paralysis in Children George Kuruvilla, MS(ENT); Shirley Perry, APN; Beverly Wilson, MD; Hamdy El-Hakim, FRCS(Ed), FRCS(ORL) Objective: To outline the natural history of vincristine- dren (1 girl, 8 boys, and 1 with sex omitted) were de- induced laryngeal paralysis (VLP) in children. scribed in the English-language literature. Four children had unilateral vocal fold paralysis only, all left-sided. The Design: Retrospective case series and review of re- median age was 2.6 years. Acute lymphoblastic leuke- ported cases in the English-language literature. mia was the underlying diagnosis in 8 patients. Two pa- tients had Down syndrome, and 1 patient had Charcot- Setting: Tertiary pediatric center. Marie-Tooth disease, type 1. Only 2 patients required tracheotomies, and 1 patient was treated temporarily with Patients: The study included all children with a con- bilevel positive-pressure ventilation. The median dura- firmed diagnosis of VLP by inspection and with com- tion of paralysis was 6.8 weeks. The prevalence of VLP plete clinical information. The sources for patient iden- was 1.36%. tification were a prospectively kept database and a review of the English-language literature, conducted on PubMed Conclusions: The data suggest that VLP is probably since 1966, as well as a bibliography search. underreported and possibly underdiagnosed. Endo- Main Outcome Measures: Charts and literature were scopic inspection is a must in all patients with airway reviewed for demographics, primary diagnosis, other di- symptoms who are receiving vicristine therapy. Early rec- agnoses, and duration and method of treatment. The ognition of VLP is mandatory, as it is reversible, has a prevalence of VLP, locally, was also calculated. good prognosis, and usually needs only interruption of vincristine therapy and conservative treatment. Results: Four children (3 boys and 1 girl) were identi- fied in our database over a 51⁄2-year period, and 10 chil- Arch Otolaryngol Head Neck Surg. 2009;135(1):101-105 INCA ALKALOIDS WERE FIRST nary retention, and orthostatic hypoten- introduced as antineoplas- sion), cranial neuropathy, and encepha- tic agents in early 1960. lopathy. Colicky abdominal pain and They are derived from the constipation are often among the earliest periwinkle plant (Vinca manifestations of vincristine neurotoxic- Vrosea). Vincristine has a well-established ity, occurring within days of drug admin- role in the treatment of hematologic ma- istration and antedating paresthesia or re- lignant neoplasms and solid tumors.1 Vinca flex depression.4 The first sign of peripheral alkaloids act as mitotic inhibitors by bind- neuropathy is loss of deep-tendon re- ing to the protein component of microtu- flexes, which is followed by paresthesia, Author Affiliations: Pediatric bules. Their neurotoxicity is thought to oc- ataxia, foot drop, and muscle wasting.2,5 Otolaryngology Service, cur because of the binding with tubulin,2,3 Cranial neuropathy is less common than Division of Pediatric Surgery (Drs Kuruvilla and El-Hakim), where it interferes with microtubule as- autonomic or peripheral neuropathy but Division of Otolaryngology sembly, axonal transport, and secretory is associated with more morbidity. Neu- (Drs Kuruvilla and El-Hakim), functions, thereby causing primary axo- rotoxicity has been reported to involve Department of Pediatrics nal degeneration. This process has been nearly all cranial nerves. It mostly mani- (Drs Kuruvilla, Wilson, and documented by nerve biopsy and elec- fests as transient cortical blindness, occu- El-Hakim and Ms Perry), and tron microscopy.3 The most common clini- lomotor nerve dysfunction with ptosis, Division of Hematology and Oncology (Ms Perry and cal manifestations of neurologic toxicity diplopia, ophthalmoplegia, jaw pain, fa- Dr Wilson), The Stollery are peripheral neuropathy, autonomic dys- cial palsy, sensorineural hearing loss, and Children’s Hospital, Edmonton, function (eg, constipation, abdominal pain, vocal cord paralysis. Jaw pain, which rep- Alberta, Canada. paralytic ileus, bladder atony with uri- resents trigeminal nerve toxicity, can oc- (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 135 (NO. 1), JAN 2009 WWW.ARCHOTO.COM 101 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/23/2021 Table 1. Children Diagnosed as Having Vincristine-Induced Laryngeal Paralysis (VLP) in Our Institution Alternate Patient No./ Underlying Duration of Airway Associated Swallowing Feeding Chemotherapy Sex/Age, y Oncological Diagnosis Paralysis, wk VLP Intervention Neuropathy Dysfunction Route Complications 1/F/2 ALL 37.3 B T No Yes NJT No 2/M/4 ALLϩDown syndrome 20.0 B IPAP Yes Yes GT No 3/M/5 Ewing sarcoma (patient died) 7.5 B No No No NGT No 4/M/3 Rhabdomyosarcoma of the testicles 4.0 L No No Yes No No Abbreviations: ALL, acute lymphoblastic leukemia; B, bilateral; GT, gastrostomy tube; IPAP, intermittent positive airway pressure; L, left-sided; NGT, nasogastric tube; NJT, nasojejunal tube; T, tracheostomy. cur suddenly within a few hours of vincristine adminis- swallowing dysfunction manifestations (repeated coughing or tration.4 Vincristine treatment can also be associated with choking) were also documented. Endoscopic findings (unilat- encephalopathy seizures and a syndrome of inappropri- eral or bilateral laryngeal paralysis, arytenoid fixation, subglot- ate antidiuretic hormone secretion. However, these forms tic lesions, and postcricoid growth) were documented. The du- of central neurotoxicity are very uncommon.4 ration of VLP was calculated by noting the interval between onset and resolution as confirmed on endoscopic inspection. The air- It appeared to us that there are very few reports in way interventions performed in the affected population (tra- the literature that discuss vincristine-induced laryngeal cheostomy, alternate route of feeding, continuous or bilevel posi- paralysis (VLP), especially in children. The goal of our tive airway pressure, and nasal trumpet), as well as other relevant study was to review our institutional experience and the diagnoses, were documented along with relevant complica- documented cases from the English-language literature tions. The prevalence of pediatric VLP in our center was cal- in order to better understand the natural course of the culated by collecting a list of the total number of children who disease. underwent vincristine therapy from June 2002 to December 2007 from the regional pharmacy services. METHODS LITERATURE SEARCH This retrospective study was based on a prospectively kept da- An English-language literature search of indexed articles pub- tabase of surgical and endoscopic procedures (Microsoft Ac- lished between 1966 and 2007 was conducted. PubMed was cess Database version 2000), which was created and updated searched using the following MeSH terms: vincristine, vocal cord by one of us (H.E.-H.) on an ongoing basis since June 2002. paralysis, stridor, acute lymphoblastic leukemia, neuropathy, Char- Other sources of patient identification were hospital and prac- cot-Marie-Tooth disease (CMT), hereditary motor, and sensory tice medical charts. All data collected from the surgical data- neuropathy. We also checked the bibliographies of pertinent ar- base and the hospital and practice medical charts were con- ticles for other articles that might be relevant to our study. firmed and cross-checked across at least 2 of these 3 sources. All patients were treated in the same pediatric center (The Stol- lery Children’s Hospital, Edmonton, Alberta, Canada), which RESULTS serves a population of 1.7 million in North and Northwestern Canada, including the provinces of Alberta, British Columbia, Of the 293 children who received vincristine therapy in and Saskatchewan and the Yukon and Northwest territories. our center in the last 51⁄2 years, 4 developed VLP. There- We included only children younger than 17 years who devel- fore, the prevalence of the condition, locally, is 1.36%. oped respiratory symptoms after vincristine therapy for their primary malignant neoplasm and who received a diagnosis of The characteristics of these children are reported in laryngeal paralysis confirmed by endoscopy. The laryngeal mo- Table 1). Three were boys. The median age was 3.5 years bility was ascertained using a 2.2-mm flexible endoscope (LF-P (range, 2.0-5.0 years). Two children had underlying acute Pediatric Intubation Fiberscope; Olympus America Inc, Cen- lymphoblastic leukemia (ALL), and one of them also had ter Valley, Pennsylvania) with the patient under spontaneous Down syndrome. The other 2 children had underlying ventilation using intravenous propofol and remifentanil hy- Ewing sarcoma and rhabdomyosarcoma of the testicles, drochloride. Bronchoscopy was performed using a rigid bron- respectively. Bilateral VLP was noted in 3 children, and choscope (Karl Storz GmbH & Co KG, Tuttlingen, Germany) 1 child had unilateral left-sided paralysis. The median du- to visualize the subglottis, trachea, and bronchi. Arytenoid fixa- ration of paralysis was 13.8 weeks (range, 4.0 to 37.3 tion, subglottic lesions, and lesions that could affect cord mobil- weeks). One boy required bilevel intermittent positive ity were ruled out. The diagnosis was, by definition, confirmed in children who had no airway-, voice-, or swallowing-related airway pressure, and 1 girl needed a tracheostomy, symptoms before the initiation of vincristine therapy. whereas the other 2 children
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