Headache and other complications following intrathecal chemotherapy administration

To the Editor:

Intrathecal chemotherapy (IC) is administered invasively by performing a lumbar puncture, and is widely used in hematological and systemic malignancies with either prophylactic or therapeutic intention. The aim of this study was to describe the incidence of headache and other complications after IC administration.

For that purpose, an observational prospective study was carried out in patients with hematologic or systemic malignancies receiving one or successive IC medications in a single tertiary hospital from July 2012 to December 2014. Neurology residents in their second year of training performed all the procedures. Lumbar punctures were performed with 20G Quincke spinal needles inserted in the L2-L3 or L3-L4 interspace; patients were placed in their lateral decubitus position with knees flexed; local anaesthesia with either bupivacaine or mepivacaine was used, and the volume of liquid collected was equal to the volume of IC medication administered afterwards. Patients were asked to drink liquids and rest in bed for the subsequent 3–4 hours on a routine basis, and personal surveys were conducted within three to seven days after IC administration.

During the study, 97 IC administrations were performed in 30 patients. The most prevalent underlying pathology was non-Hodgkin’s lymphoma and the most frequent IC combination was methotrexate, cytarabine and hydrocortisone ; the aim was prophylactic in 75% of the administrations. The median age of patients was 55.0 (35.0-67.5), 33.3% were female and the median number of IC administrations per patient was two. Headache was reported in 10 procedures (10.3%) and in six patients (20% of patients), and the median duration of the headache ranged between four and 36 hours with a median of 15 hours. Five patients took oral analgesics, acetaminophen, ibuprofen or dexketoprofen to alleviate the headache, and no blood patch was needed. Patients having headache once may have it in subsequent procedures, as headache recurred in 50% of the sample. Other complications observed were lumbar pain in seven patients and transient paraesthesia in the legs of a single patient. Ten patients had a least one of the above-mentioned complications and three had two complications, headache and lumbar pain. Severe complications were not observed in this study.

Headache attributed to intrathecal injection has been included in the International Classification of Headache disorders since its second edition (1). However, no reports on the incidence of this phenomenon have been found related to IC administration. Apart from the adverse events related to the lumbar puncture itself, patients receiving IC are also exposed to the inherent toxic effects of the chemotherapy drugs and neurotoxicities have been attributed to IC, including spinal cord lesions, seizures, and encephalopathy (2).

Our study shows that IC-related complications are frequently mild, but may occur as often as in a third of patients. Prophylactic strategies are needed in order to minimize the incidence of bothersome complications in this particularly vulnerable population.