A Pediatric Case of Hypocalcemic Seizure Associated with COVID-19 Infection
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Coronavirus disease 2019 (COVID-19) has extrapulmonary features, including acute neurological manifestations. Although the incidence of seizures or epilepsy after COVID-19 infection is relatively low, COVID-19 may impair neurological function through its effects on brain endothelial cells, inflammation, and cytokine storms, and it can cause cortical hyperexcitability through metabolic disturbances [1]. Hypocalcemia is notably prevalent among COVID-19 patients, and low ionized calcium levels in the cerebrospinal fluid can heighten central nervous system excitability, leading to seizures. In this report, we present a case of hypocalcemic seizures with COVID-19 in an adolescent boy.
A 15-year-old boy presented with one episode of tetany and two episodes of bilateral tonic-clonic seizures. Three days before his COVID-19 diagnosis, he developed a fever and chills. On the day his COVID-19 infection was confirmed, he reported involuntary muscle contractions in both hands, which persisted for 1 hour. On the fifth day of self-quarantine, he suffered a bilateral tonic-clonic seizure lasting 30 minutes. He experienced another seizure of the same type on the seventh day; this one lasted for 2 minutes and was followed by post-ictal sleep lasting 1 hour. He was admitted to the emergency room the day after his self-isolation period ended.
The patient had been vegetarian since birth because his parents were vegetarians, and he followed a lacto-ovo-vegetarian diet, including dairy products such as milk and eggs but excluding meat, fish, and poultry. After he was diagnosed with COVID-19, he exhibited a diminished appetite, resorting solely to a diet of juices for several days. He had a medical history of self-limited epilepsy with centrotemporal spikes, which began when he was 8 years old. He was treated with oxcarbazepine for 3 years, and the medication was discontinued after he experienced no further seizures.
He was mentally drowsy, and his vital signs were within the normal range, with a pulse of 92 beats per minute, blood pressure of 130/80 mm Hg, respiratory rate of 20 breaths per minute, and oxygen saturation at 100% on room air. The initial laboratory results showed a combination of normal and abnormal findings, with total calcium at 4.8 mg/dL (reference range, 8.8 to 10.2), ionized calcium at 0.76 mg/dL (reference range, 1.13 to 1.32), magnesium at 2.0 mg/dL (reference range, 1.8 to 2.4), phosphorus at 3.7 mg/dL (reference range, 2.7 to 4.7), parathyroid hormone at 358 pg/mL (reference range, 15 to 65 pg/dL), 25-OH vitamin D below 3.5 ng/mL (reference range, 32 to 100), and 1,25-OH vitamin D at 20.87 pg/mL (reference range, 19.6 to 54.3). Upon physical examination, both Trousseau’s and Chvostek’s signs were positive. Electrocardiography showed a prolonged QT interval of 506 ms (Fig. 1). Brain magnetic resonance imaging and angiography did not reveal any specific findings. Electroencephalography (EEG) demonstrated occasional sharp wave discharges from bilateral frontal areas, background slow waves, and intermittent generalized slow waves, suggesting diffuse cerebral dysfunction (Fig. 2A).
Electrocardiography showed a corrected QT interval of 506 ms. aVR, lead augmented vector right; aVL, lead augmented vector left; aVF, lead augmented vector foot.
(A) Awake electroencephalography (EEG) showing occasional sharp waves in the bilateral frontal area, background slow waves, and intermittent generalized slow waves, indicating diffuse cerebral dysfunction. (B) Follow-up awake EEG showing improvement, with mild cerebral dysfunction remaining.
The patient received a bolus of 10% calcium gluconate (20 mL) and intramuscular cholecalciferol (200,000 IU), followed by a continuous infusion of 10% calcium gluconate at a rate of 2 mg/kg/hr through the central line. Subsequently, he was prescribed oral calcium carbonate (500 mg, three times daily) and vitamin D3 (2,000 IU, once daily). His follow-up total calcium levels were recorded as follows: 6.7 mg/dL on the second day of hospitalization, 7.6 mg/dL on the third day, and 8.7 mg/dL on the sixth day. In response to the increasing calcium levels, the dosage of oral calcium carbonate was adjusted to 1,000 mg three times daily starting from the sixth day of admission. The patient experienced no seizures during his hospital stay. Follow-up EEG indicated an improvement in mild diffuse cerebral dysfunction, suggesting a transient encephalopathy due to hypocalcemia (Fig. 2B). He remained mentally alert and was discharged on the ninth day of admission with a calcium level of 8.1 mg/dL. A month after discharge, during a visit to the outpatient department, his levels of calcium, phosphorus, and ionized calcium were all within the normal range (9.5, 4.6, and 1.12 mg/dL, respectively). He continued to receive periodic follow-up examinations for 1 year while on vitamin D supplementation therapy, with no seizures reported during this time. However, he was lost to follow-up after this 1-year period.
COVID-19 is associated with acute neurological manifestations, particularly encephalopathy and stroke [1]. Although the absolute risk of seizures in patients with COVID-19 is low, EEG studies have frequently detected interictal epileptiform abnormalities in these individuals [2,3]. COVID-19 may induce cortical hyperexcitability due to metabolic disturbances. The connection between hypocalcemia and COVID-19, however, remains unclear. Research has consistently shown that hypocalcemia is common among COVID-19 patients and is associated with severe outcomes, including organ failure, increased admissions to intensive care units, higher needs for mechanical ventilation, and increased mortality [4].
Calcium ions are involved in nearly every aspect of the viral life cycle, including the control of virion structure formation, facilitation of viral entry into cells, regulation of viral gene expression, post-translational modification of viral proteins, and management of virion maturation and release [5]. The impact of COVID-19, which heavily depends on calcium, on serum calcium levels remains unclear. Disturbances in calcium balance among patients with severe infections and high viral loads could potentially result in decreased calcium levels in the bloodstream.
Vitamin D deficiency arises from insufficient dietary intake of vitamin D-rich foods and inadequate exposure to sunlight. It has been associated with severe COVID-19, leading to debates about the potential advantages of vitamin D supplementation in treating COVID-19 [6]. This is attributed to the significant impact of circulating vitamin D levels on the immune response, cellular response, and protection against severe microbial infections [7].
Our patient consumed a lacto-ovo-vegetarian diet, which typically does not lead to a severe deficiency in calcium intake. During his COVID-19 self-isolation, he experienced limited sunlight exposure and likely experienced inadequate nutrition due to insufficient meal consumption. In cases of vitamin D deficiency, it is hypothesized that following a COVID-19 infection, the worsening of hypocalcemia—potentially influenced by viral mechanisms and a lack of vitamin D—could trigger seizures. This patient, who experienced a hypocalcemic seizure in association with COVID-19, underscores the importance of recognizing and managing electrolyte imbalances in individuals with viral infections, particularly those with dietary restrictions and limited sun exposure. Maintaining optimal calcium levels is essential, as evidenced by the resolution of seizure episodes following the correction of hypocalcemia. This case highlights the potential role of vitamin D deficiency in exacerbating the clinical progression of COVID-19, calling for further research into how adequate vitamin D levels might mitigate disease severity.
The patient's legal caregiver provided written informed consent for the publication of the patient's clinical details and other related information. This study received approval from the Institutional Review Board of Inje University Busan Paik Hospital, Busan, Korea (approval number: 2023-05-030).
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Author contribution
Conceptualization: BYR and JEL. Data curation: BYR and JEL. Methodology: BYR and JEL. Project administration: BYR, BLL, and JEL. Visualization: BYR and JEL. Writing-original draft: BYR and JEL. Writing-review & editing: BYR, BLL, and JEL.