Olfactory sensory phenomena as the main seizure type in a child with low-grade glioma: a case report

Highlights

• •OSP can occur as the sole seizure manifestation in pediatric focal epilepsy.
• •The subtle nonmotor presentation of OSP may delay diagnosis.
• •Misdiagnosis as reflux shows need to consider epilepsy in recurrent sensory symptoms.
• •Neuroimaging can rule out underlying structural etiology such as low-grade glioma.

Abstract

Olfactory sensory phenomena (OSP) are a rare and often underrecognized descriptor of seizures without observable clinical manifestations, particularly in children. We report a case involving a 7-year and 9-month-old boy who experienced OSP as the sole seizure manifestation for nearly a year, resulting in a delayed diagnosis. Symptoms were initially misattributed to gastroesophageal reflux but gradually progressed to include focal impaired consciousness seizures. Brain magnetic resonance imaging revealed a mass lesion involving the right optic nerve, hypothalamus, and medial temporal lobe, leading to the diagnosis of focal epilepsy owing to a structural etiology. Histopathological assessment confirmed a low-grade glioma (LGG). Because OSP persisted despite lacosamide therapy, perampanel (PER) was introduced based on prior reports of its efficacy in epilepsy associated with glioma; however, instead of reducing, the OSP frequency increased after PER initiation. This case highlights the diagnostic challenge posed by nonmotor seizures with subtle clinical presentations and underscores the importance of considering epilepsy in patients with recurrent, unexplained sensory symptoms such as abnormal smells or nausea. It also contributes to the limited literature on pediatric focal epilepsy associated with LGG, providing educational value for physicians less familiar with atypical seizure semiology.

1. Introduction

Olfactory sensory phenomena (OSP) are classified as one of the descriptors of seizures without observable clinical manifestations [1]. OSP are rare and are typically reported as an aura; however, reports of OSP as the primary seizure type remain limited [2]. This report presents a pediatric case of focal epilepsy in which OSP represented the predominant seizure type associated with a low-grade glioma (LGG).

2. Case presentation

A 7-year and 9-month-old boy with an unremarkable perinatal and medical history demonstrated normal developmental milestones before seizure onset. No family history of epilepsy, neuromuscular disorder, or febrile seizures was reported. He was right-handed. At 4 years and 8 months, recurrent episodes involving the perception of unpleasant odors, followed by nausea, occurred approximately 5 times per day. A diagnosis of gastroesophageal reflux disease was initially made by the referring physician, and conservative follow-up was initiated, but the symptoms persisted for approximately 1 year. Two weeks before presenting to our hospital at the age of 5 years and 8 months, he began experiencing daily focal impaired consciousness seizures (FIC) with observable manifestations (semiology: olfactory aura → epigastric aura → dialeptic seizure). Physical examination results were normal. Neurological assessments revealed visual impairment in the right eye—visual acuity was limited to hand motion—while the left eye maintained a normal acuity of 1.0. No additional abnormalities were observed. Routine hematological, biochemical, and endocrine evaluations were within normal limits. Interictal electroencephalography (EEG) during light sleep revealed spike- and spike-and-slow-wave complexes in the right frontal and temporal regions. Video EEG captured seizures originating from the right temporal lobe and seizure semiology consistent with FIC. Brain magnetic resonance imaging (MRI) revealed a mass lesion extending from the right optic nerve and hypothalamus to the medial temporal lobe (Fig. 1). Tumor biopsy confirmed the diagnosis of LGG. The patient was diagnosed with focal epilepsy with a structural etiology. Unpleasant odors and nausea were interpreted as focal preserved consciousness seizures, similar to that of OSP. Lacosamide (LCM) was initiated at 5 years and 8 months, leading to the resolution of the FIC; however, OS persisted. Perampanel (PER) was subsequently added but resulted in a marked exacerbation of OS. While chemotherapy was not indicated, it was initiated for the LGG, during which FIC temporarily recurred before gradually resolving. As monotherapy with LCM failed to fully control the seizures, levetiracetam was added, but the OS remained unchanged (Fig. 2).

Fig. 1.

Head magnetic resonance imaging images. (A) T1-weighted image, (B) T2-weighted image, (C) T1-weighted image with gadolinium contrast, and (D, E) FLAIR images. A mass lesion with low signal intensity was observed extending from the right optic nerve and hypothalamus to the right medial temporal lobe on the T1-weighted image, with high signal intensity on T2-weighted and FLAIR images. No contrast enhancement was observed in the lesions. MRI, magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery.

Fig. 2.

The clinical course of the patient, showing seizure manifestations, antiseizure medication dosages, and major clinical events. The upper panel shows seizure manifestations: olfactory sensory phenomena (OSP, blue bar, times/day), OSP clusters (blue arrows), and focal impaired consciousness seizure (FIC) clusters (red arrows). Major clinical events are indicated using black arrows (magnetic resonance imaging [MRI], initiation of chemotherapy). The lower panel shows the dosages of antiseizure medications: lacosamide (LCM, red bar, mg/kg/day), perampanel (PER, blue bar, mg/day), and levetiracetam (LEV, purple bar, mg/kg/day). The maximum dosages were as follows: LCM, 12 mg/kg/day; PER, 2 mg/day; and LEV, 25 mg/kg/day. OSP frequency reached up to 5 times/day. Despite the resolution of FICS with LCM, OSP persisted and was temporarily worsened by PER. Chemotherapy was started for low-grade glioma, during which FICS temporarily recurred before resolving. LEV was later added; however, OSP remained unchanged.

3. Discussion

OSP involves the olfactory cortex, amygdala, lateral insula, and olfactory bulb [3]. A study from an epilepsy center in Italy reports that, among 1381 patients with focal epilepsy, 71 (5.1 %) experienced OSP as an aura. Of these, 58 patients (81.7 %) had an epileptogenic focus in the temporal lobe, and 16 showed abnormal MRI findings, including five with tumors [2]. These findings suggest that OSP often originates in the temporal lobe and may be associated with tumorous lesions. In epilepsy cases where OSP is the predominant seizure type, neuroimaging should be performed to rule out a structural etiology.

In this case, although the patient had been experiencing OSP multiple times daily for a year before presentation—without impaired consciousness—these episodes were not recognized as seizures. A study reports a case of temporal lobe epilepsy in which OSP without impaired awareness was the predominant seizure type for several years before FIC emerged [4]. Although OSP as the predominant seizure type is rare, the greater merit of this case lies in its educational value. Subtle sensory symptoms, such as olfactory or epigastric auras, may be easily overlooked or misattributed to non-neurological conditions, yet they should be recognized as potentially epileptic manifestations in both children and adults, until proven otherwise. This case underscores the importance of considering epilepsy in patients presenting with recurrent, unexplained sensory phenomena, particularly for pediatricians and general physicians who may be less familiar with atypical seizure semiology.

PER, which antagonizes glutamate receptors, has demonstrated efficacy in adult patients with epilepsy associated with glioma [[5], [6], [7], [8], [9]] (Table. 1). Because OSP persisted despite lacosamide therapy, PER was introduced in our case based on the reports of its effectiveness in epilepsy associated with LGG. However, instead of reducing, the frequency of OSP increased after PER initiation. Although the mechanism underlying this paradoxical effect remains unclear, pediatric data on PER in LGG-related epilepsy are scarce, and this case illustrates that its efficacy may not be universal. Further studies are needed to clarify the role of PER in in epilepsy associated with LGG in children.

Table 1.

Reported cases of focal epilepsy caused by low-grade glioma (LGG) treated with perampanel (PER).

	Number of cases	Effective	Worsening	Dosage of PER
Vechet. 2017	12	9	1	2–12 mg/day
Dunn-Prio. 2018	12	12	0	4–8mg/day
Izumoto. 2018	12	10	0	4–8mg/day
Maschio. 2019	11	9	0	6–10 mg/day
Chonan. 2020	18	18	0	2–8mg/day

We conducted a PubMed search on July 1, 2024, to review the efficacy of PER in epilepsy associated with LGG. All reported cases involved adults; no pediatric cases have been documented to date. PER dosage varied across studies; however, overall, a high efficacy in seizure control was observed. Only one case of seizure exacerbation has been reported in the literature.

4. Conclusion

This report presents a case of focal epilepsy caused by LGG, in which OSP is the only recognized seizure manifestation, leading to delayed diagnosis. This case underscores the educational value of recognizing atypical sensory symptoms as seizures and contributes to the limited literature on pediatric focal epilepsy associated with LGG. It further adds to the scarce reports indicating that PER may not always be effective and, in some instances, may even exacerbate seizure manifestations in pediatric focal epilepsy associated with LGG.

Data statement

Research data includes sensitive or confidential information such as patient data.

Informed consent

Consent was obtained from the patient’s parents both to publish the information in this case report.

Ethical statement

Ethical review was waived because of the nature of the case report, and informed consent was obtained from the parents.

Declaration of generative AI in scientific writing

Nothing to disclose.

CRediT authorship contribution statement

Takato Akiba: Writing – review & editing, Writing – original draft, Formal analysis, Data curation. Shinpei Abe: Writing – review & editing, Data curation, Conceptualization. Junya Fujimura: Writing – review & editing, Data curation. Hiromichi Shoji: Writing – review & editing, Supervision.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Glossary

PER

perampanel

LGG

low-grade glioma

LCM

lacosamide

OS

olfactory seizure

EEG

electroencephalography

FIC

focal impaired consciousness seizures

MRI

magnetic resonance imaging