Lacosamide-Induced Downbeat Nystagmus

Sir, A 69-year-old woman with prior medical history of depression and gastroesophageal reflux disease presented with headache, seizures, and fever. Her seizures were characterized by clonic movements of bilateral upper extremities. She was placed in continuous video-electroencephalography (VEEG) that showed generalized periodic epileptiform discharges. Levetiracetam 4500 mg IV was started, and her maintenance dose was levetiracetam 1500 mg BID and lacosamide 100 mg BID. On the following day, patient was noted to be aggressive and agitated. Levetiracetam was discontinued, and valproic acid was started. A brain magnetic resonance imaging was normal, and her cerebrospinal fluid analysis was positive for herpes simplex virus 1. She received a total of 21 days of IV acyclovir with improvement of her headaches and seizures, but some mild cognitive impairment was persistent, as well as confusion. VEEG showed focal slowing, and epileptiform discharges suggest focal cerebral dysfunction with epileptogenic potential over fronto-central areas. The dose of lacosamide was increased, and valproate was tapered and discontinued. After two weeks of lacosamide monotherapy, her dose was increased from 200 mg BID to 250 mg BID IV. Following two weeks on this regimen, abnormal eye movements were observed. Interestingly, after 15–20 minutes of receiving lacosamide 250 mg IV, patient developed acute downbeat nystagmus [Video 1]. The nystagmus would stop within 5–10 minutes after onset. These findings were observed for three days. The patient was worked up with repeated brain MRI, cranial CT scan, and a comprehensive metabolic panel, which were normal. Lacosamide was decreased from 250 mg BID IV to 200 mg BID IV, and her abnormal eye movements disappeared [Supplementary Material 1]. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1.","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"neurol-india.Neurol-India-D-24-00895video1.mp4"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Table 1: Summary of previous reported and presented cases with epilepsy and lacosamide-induced downbeat nystagmusIn this context, downbeat nystagmus is commonly observed in patients with epilepsy who are on antiseizure medications (ASMs).[1] The occurrence of nystagmus has been associated with supratherapeutic and also therapeutic doses of ASMs. We reviewed the PubMed literature and found only one case of lacosamide-induced downbeat nystagmus [Table 1].[1] The Naranjo algorithm was applied to assess the probability that the observed adverse drug reaction was directly attributable to the drug, as opposed to being influenced by other external factors.[2] Interestingly, the oscillopsia was continuous and without an evident fluctuation with drug intake in the case of Wu et al., but in our patient, an apparent fluctuation was observed.[1] This may be explained by the fact that our patient was receiving intravenous formulation and the report by Wu et al. that the patient was receiving oral lacosamide.[1] There is only one other report regarding nystagmus in the setting of lacosamide use. Hu et al. described a case of a young adult with focal epilepsy after traumatic brain injury. He was taking carbamazepine, but due to liver impairment, his antiseizure medications were changed to lacosamide and lamotrigine.[3] His regimen was lacosamide 100 mg/day, which was increased to 200 mg/day. A routine EEG revealed horizontal nystagmus during eye closure. Lacosamide was reduced to 100 mg/day, and he had complete improvement of the eye movements. It is worth mentioning that the present report was the only one to reveal a time–dose relationship with lacosamide intake and also the only one to be on lacosamide monotherapy. The articles of Wu et al. and Sasaki et al. reported patients taking lamotrigine, which is a drug well known to be associated with nystagmus.[1,4] Furthermore, Sawyer et al. reported vertical nystagmus in a dog (Labrador mix) who ingested several lamotrigine tablets.[5] In a review of the eye disorders related to antiseizure medications, topiramate and lamotrigine were commonly associated with eye-related side effects.[1] However, lacosamide was rarely associated, and the most common findings were diplopia and metamorphopsia.[1] Downbeat nystagmus is believed to arise from dysfunction within the vestibulocerebellum. Also, it is worth mentioning that cerebellar Purkinje neurons express voltage-gated sodium channels.[1] Therefore, antiseizure medications altering these voltage-gated sodium channels may lead to abnormalities in the vestibulocerebellum, resulting in downbeat nystagmus. 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 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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