A 14-year-old previously healthy boy presented by emergency medical services (EMS) to the emergency department (ED) for seizure-like activity. He was at school, drinking water from his water bottle, when he collapsed and his whole body began shaking. EMS was called and when paramedics arrived the boy was still having abnormal movements so he was given a dose of intranasal midazolam, which stopped the movements.
When he presented to the ED he was awake but slow to answer questions. His Glasgow Coma Scale score at that time was 15. He stated that the water in his bottle had a bitter taste to it and that he felt “funny” prior to having the movements. His initial vital signs were heart rate of 133 beats per minute, blood pressure of 116/43 mm Hg, respiratory rate of 30 breaths per minute, oxygen saturation of 97% on room air, and body temperature of 99.2°F. On physical examination, he was alert and had mydriasis, dry skin, facial flushing, rigid body posture, and intermittent tonic movements of his extremities. Soon after arrival to the ED, he had a series of jerking movements of his torso and bilateral upper and lower extremities with jaw clenching that could not be stopped with intravenous (IV) lorazepam. During moments of decreased movements the patient was able to turn his head toward the speaker and nod his head when spoken to. He then developed a fever that rose to 102°F. Due to the prolonged seizure-like activity and disordered breathing, he was intubated and given IV levetiracetam. The abnormal movements finally ceased with IV etomidate. At that time, based on his history and presentation, seizures were high on the differential diagnosis, either from toxin ingestion or primary seizure disorder; however, a dystonic reaction and infection could not be ruled out.
His initial laboratory studies were significant for serum bicarbonate of 9 mEQ/L, blood urea nitrogen (BUN) of 17 mg/dL, creatinine of 1.33 mg/dL, and creatine kinase of 213 units. Urine toxicology was positive for benzodiazepines; however, he had received lorazepam in the ED. Initial venous blood gas showed pH of 6.94, partial pressure of carbon dioxide of 63 mm Hg, lactate of 20 units, and base excess of −19.5 mEQ/L. His urinalysis was significant for moderate blood, but the color was yellow and hazy and specific gravity was 1.015; it was also negative for glucose, ketones, nitrites, and leukocyte esterase. An initial head computed tomography (CT) scan demonstrated a small area of hypo-attenuation in the white matter. The episodes were captured on electroencephalogram (EEG) but had no electrographic correlate; they just showed diffuse slowing or excessive beta activity.
Given his constellation of symptoms, including tachycardia, hyperthermia, mydriasis, facial flushing, and abnormal movements, there was a concern for ingestion of an unknown substance. Poison control was called and toxicology was later consulted. Poison control recommended proactive cooling and a lumbar puncture (LP) if the fever persisted. The LP showed unremarkable cerebral spinal fluid (CSF) studies, including polymerase chain reaction testing for herpes simplex virus. Further history revealed that both parents were pharmacists and the father noticed that several days prior an old bottle from their bedroom containing medicine tablets, including aloin, strychnine, belladonna, and senna, had gone missing. The parents then found this bottle in their son's room with an unknown number of pills missing.
In the pediatric intensive care unit, the patient continued to have generalized rhythmic myoclonic movements with tachycardia up to 300 beats per minute during these episodes. He was initially started on a continuous infusion of midazolam, but his spasms continued. He was then started on a dexmedetomidine drip that eventually stopped the movements. There were no EEG correlations with these movements. The day after admission, his BUN increased to 23 mg/dL, creatinine to 2.38 mg/dL, and CK to 6,000 units, and he had little urine output. Nephrology was consulted and diagnosed the patient with acute kidney injury with acute tubular necrosis secondary to rhabdomyolysis. On his third day of admission, he continued to have muscle spasms every 5 to 10 minutes, with his CK reaching 9,094 units, BUN 48 mg/dL, and creatinine 6.37 mg/dL, with continued decreasing urine output. Mannitol was given to increase urine output and the patient was hydrated with lactated Ringer's solution. Brain magnetic resonance imaging was performed because of the initial abnormal result on the head CT scan, and it showed several punctate foci within subcortical white matter, most likely prominent perivascular spaces.
Throughout the course of the admission, he continued to have intermittent muscle spasms that decreased with the midazolam and dexmedetomidine. His urine output improved as his BUN and creatinine continued to trend downward, and he was started on a low-potassium diet once he was weaned off sedation. He remained on levetiracetam for seizure prophylaxis and continued to work with physical therapy on strength and ambulation.
Psychiatry was consulted due to concern for suicide, as the intent of ingestion was initially unclear. Several days after admission, the patient admitted to having depression and anxiety since 6th grade, along with feelings of helplessness, hopelessness, and worthlessness. He had never told his parents about this but was involved in group therapy with the school counselor once a week. He at first denied that he tried to kill himself, but on further questioning revealed that he hated his life so he poisoned himself with strychnine. The patient was stabilized with supportive care and transferred to an inpatient psychiatric facility for further management.
Strychnine is a white, odorless, bitter-tasting crystalline powder derived from the plant Strychnos nux-vomica, which is found in southern Asia and Australia.1 In the past, it was used as a remedy for cardiovascular and respiratory problems and was most commonly found in Easton's syrup, a nonspecific stimulant.2 It was also used to treat nonketotic hyperglycinemia, a rare inborn error of metabolism resulting in elevated levels of glycine in the CSF and blood, due to its specific mechanism of action on the glycine receptor.3 In the 1920s, it was taken off the market for human consumption due to its subtle but toxic effects,4 and in the 1980s it was eliminated as an indoor pesticide due to accidental ingestions by small animals. Currently, it is only approved in the United States as a restricted use pesticide or for below-ground use to control rodents and gophers;5,6 it is completely banned in some countries.7 It can also be found in herbal medicines6 and mixed with other drugs such as lysergic acid diethylamide (LSD), heroin, and cocaine.1
In the central nervous system, strychnine is a selective competitive antagonist of glycine and acts on postsynaptic membrane receptors. Glycine is an inhibitory neurotransmitter that acts on motor neurons and interneurons in the spinal cord. As an antagonist to an inhibitor, strychnine lowers the threshold for cell activation. In the spinal cord, it causes increased reflex excitability resulting in simultaneous muscle contraction.8 Some studies have shown that it can potentially increase the risk of having seizures because the build-up of glycine in the synapse affects strychnine-insensitive glycine receptors that, in turn, act on excitatory N-methyl-D-aspartate receptors.9
Strychnine has a rapid onset of action and is primarily metabolized in the liver, with a small percentage excreted unchanged in the urine. The percentage that is excreted decreases with increasing dose of exposure, and with higher doses paralysis or death occur before the toxin can accumulate in the bladder.4 Symptoms usually occur within 10 to 20 minutes of exposure,1 with the most common symptoms being agitation, painful muscle spasms, convulsions, fever, uncontrollable arching of the neck and back (opisthotonus), facial muscle contraction (risus sardonicus), rigidity, muscle pain, and difficulty breathing. Exposure to higher doses leads to respiratory failure and death caused by asphyxia from respiratory arrest or medullary paralysis.8
Diagnosis is based on history of ingestion with subsequent development of muscle stiffness and contractions, often triggered by external stimuli.10 Laboratory findings include elevated CK, serum glutamic oxaloacetic transaminase, and lactate dehydrogenase. Strychnine can be measured in urine, serum, and gastric fluid;8 however, treatment should be initiated prior to obtaining results as patients may develop hyperthermia, lactic acidosis, and rhabdomyolysis.11 The differential diagnosis includes seizures, as seen in our patient, and tetanus, which also presents with muscle spasms, muscle stiffening, and fever.12 Because there is no specific laboratory test to diagnose tetanus and results of strychnine levels take several days to return from the laboratory, it is important to get an immunization history and ask about recent injuries or open wounds to help differentiate the two.12
Treatment is mainly supportive, focusing on airway protection, controlling muscle contractions, and fluid and electrolyte management. It is also important to provide a quiet, dim environment for the patient, as a small stimulus could trigger another attack.10 Typically, the contractions will respond to benzodiazepines along with phenobarbital. However, because benzodiazepines work on gamma-aminobutyric acid (GABA) receptors and not directly on glycine, other agents such as propofol or neuromuscular blocking agents, such as tubocurarine, can be used.8 In our case, midazolam and dexmedetomidine were used. Both are sedative agents that act on different pathways. Midazolam is a benzodiazepine, and by working on GABA, an inhibitory neurotransmitter, it causes skeletal muscle relaxation.13 Dexmedetomidine is an alpha-2 agonist that inhibits the sympathetic nervous system, resulting in decreased heart rate and blood pressure.14 It also causes sedation by acting on the alpha-2 adrenoreceptors in the locus coeruleus, an area in the brainstem where these receptors are densely concentrated and that is responsible for vigilance and response to stress.15 Along with controlling the muscle spasms, it is also important to maintain urine output greater than 1 mL/kg per hour to prevent metabolic acidosis and acute renal failure. Patients are usually conscious during the episodes, so pain control is crucial because the muscle spasms can cause intense pain.8 The prognosis for strychnine poisoning is favorable if the patient survives past the first 5 hours from symptom onset16 and if treatment is initiated within the first 6 to 12 hours after exposure.8
In the past, strychnine was known as the “silent killer” because it was white, odorless, and very toxic. In some ways, it can still be considered a “silent killer,” as many physicians have never heard of such a toxin. Although uncommon, it is an important differential to consider when a patient presents with seizure-like activity but is awake and symptoms do not respond to antiepileptic drugs. Furthermore, physicians could consider dexmedetomidine as a novel sedative agent for the treatment of benzodiazepine-resistant nonepileptic abnormal movements.
- US. Centers for Disease Control and Prevention. Facts about strychnine. https://emergency.cdc.gov/agent/strychnine/basics/facts.asp. Accessed April 30, 2019.
- Symons AJ, Boyle AK. Accidental strychnine poisoning: a case report. Br J Anaesth. 1963;35:54–56. doi:10.1093/bja/35.1.54 [CrossRef]
- Arneson D, Ch'ien LT, Chance P, Wilroy RS. Strychnine therapy in nonketotic hyperglycinemia. Pediatrics. 1979;63:369–373.
- Lindsey T, O'Hara J, Irvine R, Kerrigan S. Strychnine overdose following ingestion of gopher bait. J Anal Toxicol. 2004;28:135–137. doi:10.1093/jat/28.2.135 [CrossRef]
- Khan S. Veterinary Manual. Overview of strychnine poisoning. https://www.merckvetmanual.com/toxicology/strychnine-poisoning/overview-of-strychnine-poisoning. Accessed April 22, 2019.
- Singhapricha T, Pomerleau AC. A case of strychnine poisoning from a southeast Asian herbal remedy. J Emerg Med. 2017;52:493–495. doi:. doi:10.1016/j.jemermed.2016.10.007 [CrossRef]
- Prat S, Hoizey G, Lefrancq T, Saint-Martin P. An unusual case of strychnine poisoning. J Forensic Sci. 2015;60:816–817. doi:. doi:10.1111/1556-4029.12706 [CrossRef]
- Borges A, Abrantes J, Teixeira M, Parada P. Strychnine. http://www.inchem.org/documents/pims/chemical/pim507.htm#PartTitle:14.%20AUTHORS,%20DATE. Accessed April 22, 2019.
- Larson AA, Beitz AJ. Glycine potentiates strychnine-induced convulsions: role of NMDA receptors. J Neurosci. 1988;8:3822–3826. doi:. doi:10.1523/JNEUROSCI.08-10-03822.1988 [CrossRef]
- Rentmeester L, Ly B. Strychnine poisoning. https://calpoison.org/news/strychnine-poisoning. Accessed April 22, 2019.
- van Berlo-van de Laar IR, Arbouw ME, Bles CM. [Strychnine poisoning: uncommon, but does still happen]. [Article in Dutch]. Ned Tijdschr Geneeskd. 2015;159:A8877.
- US. Centers for Disease Control and Prevention. Tetanus. For clinicians. https://www.cdc.gov/tetanus/clinicians.html. Accessed April 30, 2019.
- Duval A, Malecot CO, Perchenet L, Piek T. The benzodiazepine midazolam preferentially blocks inactivated Na channels in skeletal muscle fibre. Naunyn Schmiedebergs Arch Pharmacol. 1993;347:541–547. doi:. doi:10.1007/BF00166748 [CrossRef]
- Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001;14:13–21. doi:10.1080/08998280.2001.11927725 [CrossRef]
- Samuels ER, Szabadi E. Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation. Curr Neuropharmacol. 2008;6:235–253. doi:. doi:10.2174/157015908785777229 [CrossRef]
- Babu K. Strychnine poisoning. UpToDate. https://www.uptodate.com/contents/strychnine-poisoning. Accessed April 22, 2019.