Article, Neurology

Synthetic cannabinoid receptor agonists-induced recurrent seizure in elderly patient

a b s t r a c t

Abuse of synthetic cannabinoid receptor agonists (SCRAs) has been associated with Young individuals. The abuse of SCRAs is very rare in elderly people, but a few cases highlight the SCRAs-induced side effects. These substances lead to a variety of clinical and Psychiatric symptoms including seizures. Here we report recurrent seizures after SCRA abuse by an elderly patient.

(C) 2019

Background

Abuse of synthetic cannabinoid receptor agonists (SCRAs) has been associated with young individuals due to their inexpensiveness and easy accessibility via the internet. These substances lead to a variety of clinical and psychiatric symptoms [1-4]. The abuse of SCRAs is very rare in elderly people, but a few cases highlight the SCRAs-induced side effects. The reported cases involve cardiovascular-related health adverse effects [5-7].

Marijuana is well-known herbal stimulant on cannabinoid receptors (CB). One of the psychoactive chemical compounds in the marijuana plant is ?9-tetrahydrocannabinol (THC). Unlike THC, which is a partial agonist, SCRAs are full agonists on CB receptors. Synthetic cannabinoid receptor agonists bind with higher affinity and intrinsic efficacy exerting stronger effects [8-12].

Seizures from THC are unlikely and very rare in adults, but cases of seizure from accidental pediatric marijuana ingestion have been re- ported. In these Pediatric cases, the seizure is believed to be a complica- tion of marijuana-induced encephalitis [13-17]. In contrary, SCRAs- induced seizures have been reported in younger patients and the symp- toms may be delayed, or occur acutely. Animal studies have confirmed the effect of SCRAs on Seizure activity via binding to the CB1 receptors [18-20]. Here we report recurrent seizures after SCRAs abuse by an el- derly patient.

* Corresponding author at: NYMC, Metropolitan Hospital Center, 1901 First Avenue, New York, NY 10029, United States of America.

E-mail address: [email protected] (G.W. Hassen).

Case report

A 71 years old male presented to the Emergency Department (ED) with emergency medical services (EMS) after 3 episodes of seizures that lasted 2-3 min. The events were witnessed by bystanders. The type of seizure was not documented in the EMS report and no seizure-like activities were observed during his hospital stay. The pa- tient reported several seizures after K2 abuse in the past. The patient had known Hepatitis C, prostate cancer and hypertension. He was not taking any medications. He had no known drug allergies, lived in a shel- ter, smoked K2, and occasionally used alcohol and cocaine. The patient reported an episode of syncope a year before the current visit. He was noted to be have hypotension at that time. The patient denied any sei- zure disorders.

On physical examination, his initial vitals were as follows: tempera- ture: 97.6? Fahrenheit; heart rate: 68 beats per minute; blood pressure: 68/46 mmHg and oxygen saturation: 93% on room air. Initially the pa- tient was drowsy and not providing proper information, but after his mental status improved, he reported smoking K2 and experiencing sei- zure episodes after K2 abuse. No external signs of head or body trauma were present. The rest of the physical examination was unremarkable. brain computed tomography (CT) scan and chest radiography were un- remarkable. The electrocardiogram showed Sinus bradycardia at 58 beats per minute and a first degree AV block. His initial urine toxicol- ogy was negative for routine tests such as phencyclidine (PCP), THC, co- caine, opioids or benzodiazepines. His tests were negative for alcohol in both visits. His thyroid-stimulating hormon (TSH) and cardiac troponin levels were normal.

https://doi.org/10.1016/j.ajem.2019.11.014

0735-6757/(C) 2019

Chart review showed that he had one hospital admission approxi- mately a year before this presentation for syncope and 6 additional ED visits for K2-related intoxication within a 3-year period. His orthostatic blood pressure test was unremarkable. No tachycardia was present with the hypotensive episode during the hospital stay and the next day the patient signed out against medical advice.

Discussion

Several SCRAs-induced health adverse effects have been reported and one such symptom is seizures. Seizures appear to be the result of SCRAs action on CB1 receptors in the central nervous system (CNS) [21]. These receptors are localized on glutamatergic and GABAergic neu- rons [22-24]. The presumed mechanism for seizures is SCRAs-mediated glutamate-induced excitotoxicity and/or reduction of the inhibitory ef- fect of GABA. Animal studies have demonstrated that SCRAs can induce seizures, but THC does not [19]. The seizure activity in these animals was attenuated by administration of the synthetic cannabinoid receptor (SCR) antagonist rimonabant. This strongly suggests the role of CB re- ceptors in seizures. Moreover, a dose of diazepam, known to attenuated the seizure activity from the chemical convulsant agent pentylenetetra- zol (PTZ) did not affect seizure activity from SCRAs in the same experi- mental animals [19]. Benzodiazepines are the mainstay of initial treatment in a seizure episode in the ED. The fact that diazepam did not attenuate seizure activity begs the question if benzodiazepines are an optimal choice in treating SCRAs-induced seizure. Treatment with SCR antagonists could be an option and is appealing in patients with SCRAs-induced seizures, but more data is required.

Another phenomenon that requires further studies is the fact that several patients with SCRA intoxication stay for extended periods in the ED due to altered/depressed levels of consciousness. This could be secondary to non-convulsive seizures/status. We observed that patients remained altered for longer periods, despite normal routine Drug test– ing, no alcohol in their systems and normal electrolytes as well as unre- markable brain CTs [3]. A recent study showed that 5% of ED patients with Altered mental status have non-convulsive seizures/status that can only be detected with electroencephalogram [25-27]. Given the fact that seizures are one complication of SCRAs, the prolonged AMS in patients with SCRAs intoxication may suggest a non-convulsive seizure/status that is not expressed as tonic-clonic ac- tivities. Monitoring patients with prolonged AMS after SCRAs intoxica- tion with portable EEG may help identify this subgroup and start/ guide early appropriate therapy to terminate the seizure process.

Limitations

This case report relied on a patient’s admission to using SCRAs before the seizures. These symptoms occurred on several occasions after using SCRAs. There was no clear description of the seizure activity reported. In addition, the initial hypotensive state that can also result from SCRAs abuse, as well as a previous history of syncope, widens the differential diagnosis of hyper-excitation of the brain in the setting of syncope/hy- potension. Some studies have shown that SCRAs can cause bradycardia and affect cardiac contractility, leading to hypotension and syncope, which can be followed by myoclonic jerks. This is the most misleading symptom in the diagnosis of seizures. However, the recurrent nature of the reported seizure activities by the patient, and the three consecu- tive seizures reported by bystanders in relation to SCRAs abuse suggest the possibility of a true seizure. Furthermore, no laboratory testing was conducted to confirm the presence of SCRAs in bodily fluids. Moreover, the patient may have gone to other hospitals and may have had a work up that could explain his symptoms. Finally, true tonic-clonic seizure ac- tivities that may have been observed by bystanders or EMS, but may have not been documented.

Conclusion

SCRAs abuse should be suspected in elderly who present with new onset seizures and/or syncope. Identifying SCRAs abuse can help health care providers counsel patients. More studies are needed to warrant the use of SCR antagonists in the treatment of seizures from SCRAs.

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