Intrathecal Methotrexate: Pose Before You Probe

Résumé fourni par la source

To the Editor, Intrathecal methotrexate (IT Mtx) is used for treatment as well as for prophylaxis in patients with acute leukemia with central nervous system (CNS) involvement.[1] However, IT Mtx administration is associated with acute neurotoxicities like seizures.[2] Here, we present one such case where a seizure developed during the administration of IT Mtx, but the cause of the seizure was not iatrogenic. A 45-year-old male was posted for IT Mtx administration for CNS prophylaxis of diffuse large B-cell lymphoma. Since the procedure was to be done by anesthetists, preanesthetic checkup was done before it. The patient declared that he had no known comorbidities and all investigations were normal. On the day of the procedure, the patient was positioned in the lateral decubitus position, and after aseptic sterile cleaning and draping, infiltration of 2 mL of 2% lignocaine locally, a 26-G Quincke Babcock spinal needle was inserted in the L3-L4 space. After the loss of resistance, the stylet was withdrawn and cerebrospinal fluid (CSF) was seen in the needle hub. After aspiration of CSF in a drug-filled syringe, we started to inject 12.5 mg methotrexate. With the initiation of methotrexate injection, the patient started developing tonic–clonic seizures with uprolling of the eyeballs. The procedure was stopped midway, midazolam 5 mg was given intravenous and vitals were checked which was found to be normal. Postictal confusion lasted for around 30 min. There was no neurological deficit. The patient was kept under observation for the next 12 h. On further inquiring about other comorbidities of the patient once again, the mother of the patient revealed a history of seizures for the past 20 years, but the patient was not on any medications for the same. He had an episode of seizure at his home 2 years back. Magnetic resonance imaging brain was done the next day, which was found to be normal. Electroencephalography, microbiological cultures, and metabolic workup were also normal. The patient was discharged uneventfully. IT Mtx is the most common drug to prevent CNS spread of hematologic malignancies. Seizures are seen in 8%–13% of patients with acute lymphocytic leukemia, most of them occurring in the first 6 weeks of remission-inducing treatment.[3] Acute neurotoxicity is an important side effect of IT Mtx therapy and can manifest within hours to days.[4] These may include acute seizures, encephalopathy, stroke-like episodes, and chronic cognitive impairment. The neurotoxic effects of methotrexate have been attributed to various factors, including folate deficiency and elevated homocysteine levels. Imaging studies done in patients with acute Mtx toxicity are usually normal.[3] Various case reports and studies have found an association between methotrexate and seizure episodes in patients given therapy for hematologic malignancies.[1-3] In our case also, initially, we suspected the cause of the seizure to be methotrexate toxicity. However, on history taking, he was found to be a patient with a previous history of seizures not on any therapy. Literature has shown that induction of seizure only occurred after administration of IT Mtx and not while injecting the drug during the procedure itself as seen in our case.[2,3] The presence of triggering factors in the form of an afferent stimulus, such as stress, fatigue, sleep deprivation, and noncompliance with antiepileptic medications, is known to cause reflex seizures. In a patient with epilepsy, there is the presence of dynamic multifactorial facilitating and triggering factors that can modulate the seizure threshold.[5] We believe that the immediate seizure onset on methotrexate injection was precipitated due to the presence of one of these sensory triggers and his previous status of being an epileptic. Thus, our experience from this case reinforces the age-old emphasis on diligent and detailed history taking (“pose” all possible questions) from a patient before any anesthetic procedure (“probe”). Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and that due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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