Topiramate-Induced Severe Heatstroke in an Adult Patient: a Case Report Lucie Canel1*, Sofia Zisimopoulou2, Marie Besson3 and Mathieu Nendaz1
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Canel et al. Journal of Medical Case Reports (2016) 10:95 DOI 10.1186/s13256-016-0835-5 CASEREPORT Open Access Topiramate-induced severe heatstroke in an adult patient: a case report Lucie Canel1*, Sofia Zisimopoulou2, Marie Besson3 and Mathieu Nendaz1 Abstract Background: Heatstroke is a life-threatening condition defined by failure of heat load dissipation, resulting in a core temperature higher than 40 °C (104 °F) associated with neurological dysfunction. Topiramate may cause anhidrosis, potentially resulting in heatstroke, as reported especially in children. Case presentation: A 57-year-old Caucasian man was admitted to the emergency room in a febrile comatose state. After a complete workup ruling out the usual etiologies of such a condition, we assumed the hypothesis of a heatstroke caused by topiramate, recently prescribed for essential tremor. Conclusions: Topiramate-related heatstroke has been described in children but must be recognized in adults as well. Outcomes may range from total clinical recovery to persistent neurological dysfunction or death. The prescription of topiramate and the follow-up of adult patients under this medication should include an evaluation of hypohidrosis, especially in contexts of high temperature. Keywords: Topiramate, Heatstroke, Adult, Anhidrosis, Febrile coma Background topiramate-associated heatstroke in an adult patient suf- Heatstroke is a life-threatening condition defined by fering from essential tremor. failure of heat load dissipation, resulting in a core temperature higher that 40 °C (104 °F) associated Case presentation with neurological dysfunction, ranging from mild al- A 57-year-old Caucasian man was admitted to the tered mental status to coma [1]. Mortality is high emergency room in a febrile comatose state. He was among patients presenting to the hospital. Two types working as a chimney sweep and was known for hyper- can be distinguished, exertional and classical heat- tension, type II diabetes, dyslipidemia and essential stroke. Exertional heatstroke is related to strenuous tremor for which he had been prescribed topiramate 6 exercise during periods of high temperature. Classical weeks earlier, at an initial dosage of 25 mg per day. The heatstroke is favored by any mechanism decreasing dosage was progressively increased by his physician, up heat loss (anticholinergic or antihistamine drugs, ad- to 50 mg twice a day on the day of admission. Other … vanced age, high ambient temperature, ) or increas- medication included citalopram, clonazepam, allopurinol, ing heat production (sepsis, stimulant drugs, thyroid ibuprofen, mefenamic acid, metformin, esomeprazole, pro- … storm, ). Multiple organ complications are common, pranolol, losartan, torasemide, and hydrochlorothiazide. including acute respiratory distress syndrome, acute Our patient was admitted in July, and the renal failure, hepatic injuries, and rhabdomyolysis. temperature on the day of his admission reached 39.7 °C Topiramate has been described as a trigger for heat- (103.4 °F, heat index >93). The mean temperature of stroke, essentially in epileptic children, leading to an the week before was 36.6 °C (97.3 °F), making this FDA warning about monitoring patients on topiramate week the second warmest week noted in Switzerland in case of hot weather. We present here the case of a for more than 150 years, according to the national meteorological station [2]. * Correspondence: [email protected] Earlier on that day, as he was walking toward his car 1Department of Internal Medicine, HUG Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland after work, our patient suddenly lost consciousness. At Full list of author information is available at the end of the article the arrival of the ambulance, our patient was found in a © 2016 Canel et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Canel et al. Journal of Medical Case Reports (2016) 10:95 Page 2 of 4 comatose state, with a Glasgow Coma Score (GCS) of 3. fluid (CSF) remained sterile and viral polymerase chain re- He was tachypneic with a rate of 50 breaths per minute action (PCR) assays [enteroviruses, human immunodefi- with a preserved oxygen saturation and his tympanic ciency virus (HIV), herpes simplex virus (HSV), human temperature was more than 41 °C (105.8 °F), reaching the herpes virus 6 (HHV6), Epstein-Barr virus (EBV)] were maximal scale of the thermometer. His blood pressure negative, as well as blood serologies (HIV, parvovirus B19) was 110/62 mmHg and his heart rate was 89 beats and blood cultures. Toxicological analysis was only per minute. The onsite glycemia was 10 mmol/L. He positive for benzodiazepines. The electroencephalo- was intubated and then brought to the emergency gram (performed when our patient was already extu- room. Given these circumstances, the initial neuro- bated and alert) showed no sign of epilepsy. logic examination was limited, but showed no asym- The hemodynamical and neurological courses were metrical pattern, no clonus, and no hyperreflexia. quickly favorable, allowing for an extubation and a On arrival, his temperature was 40.4 °C (104.7 °F) and transfer to a regular hospital ward within 24 hours. A he became hemodynamically shocked, needing volume clinical examination after extubation was strictly normal, resuscitation with 4 liters of sodium chloride 0.9 % and including complete neurological status, and our patient administration of noradrenaline. The electrocardiogram was symptom-free. showed ventricular bigeminy and he received intra- Our patient could not recall what happened on the venous magnesium. Ceftriaxone and acyclovir were day he lost consciousness. Given our suspicion of administrated, given a primary hypothetical diagnosis heatstroke and the lack of evidence for an infectious of meningoencephalitis. disease, antibiotics and antivirals were stopped. His Table 1 depicts the blood analyses at admission and a history was completed. Our patient had spent several few hours later. They reflect a progressive multiple hours in an unusually hot environment 3 days before organ failure developing within 48 hours. A brain and the admission, while attending a meeting under a thoracoabdominal computed tomography (CT) scan tent. It has to be pointed out that the weather had with injection of radiocontrast media showed no abnor- been exceptionally hot in Switzerland during this malities except nonspecific, basilar pulmonary infiltrates period of time, with temperatures reaching record of limited interest to explain our patient’s condition. levels. When specifically asked about his sweating, Echocardiography showed a normal left ventricular ejec- our patient immediately reported a decrease in his tion fraction and no pericardial effusion. sweating since he started to take topiramate, while he A lumbar puncture showed an albuminocytologic used to sweat profusely before. dissociation (1 M/L leukocytes, 0.72 g/L proteins) The clinical and biological courses were uneventful, without oligoclonal distribution, and an augmented with a normalization of all the parameters within 1 glycorrachia (5 mmol/L). Cultures of the cerebrospinal week, except for his gamma-glutamyl transpeptidase Table 1 Laboratory values at admission and worst values within 48 hours Test Unit Value at admission Worst value within 48 h Value one week later Hemoglobin g/L 101 101 128 Leukocytes G/L 20.6 20.6 7.3 Thrombocytes G/L 181 131 377 PTT seconds >140 >140 25.5 INR 1.05 1.04 0.9 CRP mg/L 2.5 6.4 5.1 Creatinine umol/L 151 91 76 CK U/L 160 829 50 AST U/L 30 137 17 ALT U/L 34 346 64 Alkaline phosphatase U/L 39 48 72 GGT U/L 122 183 112 Total bilirubin umol/L 4 9 6 D day, PTT partial thromboplastin time, INR international normalized ratio, CRP C-reactive protein, CK creatine kinase, AST aspartate aminotransferase, ALT alanine transaminase, GGT gamma-glutamyl transpeptidase Canel et al. Journal of Medical Case Reports (2016) 10:95 Page 3 of 4 (GGT) level, which remained at the upper limits of spontaneously reported hyperthermia when they were normal, as already noted by his physician in the past. asked about side effects in general compared to 0.5 % of patients on other antiepileptics [15]. Described risk factors Discussion to develop topiramate-associated hyperthermia are young Heatstroke is a life-threatening condition resulting in age, high doses and hot weather [15]. failure of normal compensatory heat-shedding mecha- In our patient’s case, the dosage of topiramate was ra- nisms. When heat gain exceeds heat loss, the body ther low, but our patient was taking ibuprofen, mefe- temperature rises and can lead to heatstroke, defined as namic acid, losartan and diuretics, which probably a body temperature higher than 40 °C (104 °F) associated contributed to acute renal failure in this diabetic patient, with neurological dysfunction, ranging from mild altered potentially leading to an accumulation of topiramate, mental status to coma [1]. Two forms of heatstroke can since this drug is eliminated by the kidney. Unfortu- be distinguished: exertional and classical. Given the lack nately, topiramate blood levels were not requested at ad- of evidence of strenuous exercise in our patient, al- mission. They were low (9.9 umol/L, normal 15–80 though his profession could imply some physical efforts, umol/L) 2 days later, after decreasing the dosage from classical heatstroke seems to better correspond to his 50 mg twice a day to 50 mg once a day. Second, the condition: high temperature, coma, coagulation disorder, weather on the day of admission and the past few days rhabdomyolysis, hepatic injury, and renal failure.