Կեղծ դեղորայքակայունություն կասկածելի էպիլեպսիայի դեպքում.կլինիկական դեպքի նկարագրություն

Epilepsy is a chronic neurological condition characterized by recurrent unprovoked seizures. It is one of the world’s most prevalent neurological diseases, affecting nearly 50 million people worldwide [1]. The International League Against Epilepsy has defined drug-resistant epilepsy as the failure of adequate trials of two tolerated and appropriately chosen anti-seizure medications to deliver sustained seizure freedom [2]. Despite the array of anticonvulsants with different mechanisms of action, nearly one-third of individuals with epilepsy remain drug-resistant. This subset carries an even higher risk of poor outcome with increased morbidity and mortality, along with higher resource use [2].

It is essential to firmly rule out pseudo-drug resistance before diagnosing drug-resistant epilepsy. This domain includes situations where presumed treatment resistance is not true pharmacological refractoriness, but rather arises from misdiagnosis, inappropriate drug selection or dosing, partial non-adherence to therapy, and/or seizures masquerading as comorbidity disorders. In tertiary epilepsy centers, up to 15% of referred patients are pseudo-resistant [3]. A wide range of medical conditions can mimic epilepsy, including syncope, movement, sleep and metabolic disorders [4].

Among metabolic causes, hypoglycemia is particularly important due to its potential to provoke convulsive or abnormal motor phenomena [5]. One clinically significant entity that may present with recurrent hypoglycemia is insulinoma, a neuroendocrine tumor of the pancreas characterized by hyperinsulinemia. Insulinomas are rare, with an estimated incidence of 1-4 cases per million per year. They are characterized by the classic Whipple’s triad: signs or symptoms of hypoglycemia, low plasma glucose level confirmed at the time of symptoms, and resolution of symptoms after a glucose injection [6]. Due to the predominance of neurological symptoms, such patients are often misdiagnosed as having epilepsy, mental illness, or dementia.

We present the case of a patient who had been treated for presumed drug-resistant epilepsy for nearly two decades. Despite polytherapy and years of follow-up, her persistent “seizures” challenged the diagnosis. Careful reevaluation, including clinical observation, home video recordings, and metabolic workup, uncovered an entirely different underlying cause. This case underscores the importance of questioning diagnostic inertia and remaining vigilant for potentially reversible conditions that may mimic epilepsy.

CASE PRESENTATION

A 69-year-old female patient was referred to the outpatient neurology clinic with a history of epilepsy refractory to anti-seizure medications. She had been experiencing seizures for 17 years. At the time of presentation, she was taking carbamazepine 600mg/day, valproic acid 1000mg/day, and levetiracetam 1000mg/day. Despite polytherapy, her son reported almost daily seizures, sometimes multiple times a day. The eyewitnesses described the attacks as full-body stiffening and limb shaking. During the visit, the patient had no other complaints; she was alert and aware, answered questions, and followed instructions fully and appropriately. Her neurological examination was unremarkable. Her medical history included arterial hypertension, for which she was taking perindopril/indapamide/amlodipine.

Back in 2004, her first-ever long-term electroencephalography (EEG) revealed abnormalities in the form of disorganized rhythm patterns with sharp waves in the temporal leads. Further routine 20-60-minute EEG studies performed later had never showed pathological changes, and 3T brain magnetic resonance imaging (MRI) utilizing HARNESS protocol was also unremarkable. Nevertheless, the diagnosis of epilepsy was retained, leading to progressive escalation of anticonvulsants. Therapeutic serum levels of carbamazepine (7.42µg/mL, normal 4-12µg/mL) and valproic acid (51.77µg/mL; normal 50-100μg/mL) were monitored. The carbamazepine dose was gradually increased based on the reported seizure frequency.

Due to diagnostic uncertainty, her family was instructed videotape subsequent seizures. A few days later, her son brought a video recording of non-stereotypical, irregular whole-body movements lasting longer than a typical epileptic seizure. The attacks were not characterized by the classic stereotypy or logical sequence as observed in generalized tonic-clonic seizures, while her consciousness was partially retained. The movements were choreoballistic rather than clonic. These findings seriously questioned the diagnosis of epilepsy. The patient and her family persisted in refusing hospitalization and postponed the new long-term video-EEG monitoring, despite recommendations. Further increases in the carbamazepine dose yielded no benefit, and the seizure frequency remained stable.

Weeks later, the patient was brought to the emergency department with another seizure. At the time of the episode, she was alert and able to answer questions but did not consistently follow commands. She exhibited irregular jerking movements involving all extremities, breath-holding spells, and frothy discharge from the mouth. Immediate capillary glucose was checked, revealing severe hypoglycemia (glucose 1.8mmol/L, reference range: 3.3-5.5mmol/L). The episode was promptly aborted with intravenous glucose. Subsequent laboratory investigations found elevated insulin level in the blood (83.5µU/mL, normal range: 0.7-25µU/mL). Abdominal computed tomography scan revealed a pancreatic mass compatible with an insulinoma. The tumor was excised surgically. Histopathology confirmed insulinoma. The patient remained seizure-free following surgery. The anticonvulsant dosage was gradually tapered and eventually discontinued. At her most recent follow-up, she was seizure-free without taking anti-seizure medications, with no recurrence of hypoglycemia.

DISCUSSION

This case demonstrates several hot topics in epilepsy diagnosis and treatment, such as the consequences of premature diagnostic closure and the need for revisiting atypical cases.

Although epilepsy can appear at any age, idiopathic or genetic epilepsy usually develops in childhood and young adulthood. Patients with onset of a new seizure disorder after age 50 require careful evaluation for secondary causes, including cerebrovascular disease, brain tumors, infections, autoimmune and metabolic disorders [7]. In this patient, early workup (EEG and MRI) was non-contributory; however, the atypical age of onset should have prompted a higher index of suspicion for secondary etiologies.

The patient would seem to meet the definition of drug-resistant epilepsy, given that she had failed multiple anti-seizure medications at therapeutic doses. But her seizures were not epileptic. Misdiagnosis is one of the major causes of pseudo-resistance and has been recorded in up to 15% of patients attending specialized epilepsy centers [3]. These errors are associated with serious consequences: months or years of ineffective therapy, negative psychosocial burden to prolonged exposure to unnecessary medications, drug side effects, and delays in correct diagnosis.

A thorough assessment of seizure semiology is critical for making an accurate diagnosis. One should always try to observe a seizure personally or have at least a video recording. Home video recordings on smartphones, which are readily available to almost everyone, are very helpful for understanding seizure semiology, especially in cases of rare seizures [8]. In this case, the video recordings revealed atypical features: irregular, non-stereotyped movements, prolonged duration, and preserved consciousness – features inconsistent with generalized tonic-clonic seizures.

Hypoglycemia is a recognized cause of reversible neurological impairment. Severe episodes typically cause confusion, coma, or epileptiform activities. These are most often described as “bizarre” non-typical movements or behaviors, but primary or secondary bilateral tonic-clonic activities have also been reported [9]. Of note, hypoglycemia can even cause epileptiform EEG alterations, which may further obscure the diagnosis. The large variety of EEG abnormalities in hypoglycemia and lack of reliable data do not allow standardization of EEG signs for this pathology. However, the most frequently reported EEG changes are focal or diffuse slowing. As demonstrated in a literature review by Dudley A et al. (2022), ictal and interictal EEG changes in patients with insulinoma-induced hypoglycemia can range from nonspecific diffuse slowing of background activity to focal or diffuse δ- and θ-rhythms, and paroxysmal activities (spikes and sharp waves) [9]. Hypoglycemia may affect all cortical regions without any significant interhemispheric asymmetry. However, available data suggest that the topography of EEG abnormalities may change depending on serum glucose levels. Particularly, with mild hypoglycemia, these changes are more prominent in the anterior cerebral cortex (mostly the frontal cortex), in contrast to severe hypoglycemia, which predominantly affects the parietal-occipital and temporal regions [10]. In our patient, chronic low-level recurrent hypoglycemia resulted in prolonged hyperkinetic movement mimicking seizures, resulting in a correct diagnosis only 17 years after onset. The first abnormal EEG report strengthened the wrong diagnosis and led to prolonged unnecessary treatment. This highlights the need to consider basic metabolic measurement as a routine part of the workup of any patient with refractory or atypical cases, even when there is a high suspicion of epilepsy with EEG confirmation.

Insulinoma is an uncommon but important cause of recurrent hypoglycemia [11]. Neurological manifestations often prompt initial referral to a neurologist rather than an endocrinologist. Insulinoma-induced seizures are rare, but several cases have been reported in the literature [5,12]. Although the median diagnostic delay for insulinoma is not well reported, misdiagnosis and treatment delays are not unusual. In our patient, the 17-year diagnostic hiatus underscores how easily insulinoma can masquerade as epilepsy. Most patients are curatively treated with surgery, as illustrated here.

In the presented case, subsequent standard EEGs were universally normal after the first abnormal study, which may have had a low threshold level of electrographic abnormality, or there might be no specific EEG features other than some changes associated with hypoglycemia. The lack of long-term video-EEG monitoring was a significant drawback due to the patient’s frequent denial of inpatient admission. In cases that are uncertain or refractory to treatment, inpatient video-EEG remains the gold standard for differentiating epileptic and non-epileptic events [13]. Clinicians must insist on these evaluations, even in the face of family resistance.

CONCLUSION

The reported case emphasizes the risk of a misdiagnosis in epilepsy, with severe implications for the patient. A woman suffered 17 years of failed therapy with several anti-seizure medications for suspected drug-resistant epilepsy before being eventually diagnosed with repeated hypoglycemia caused by an insulinoma. A thorough re-evaluation, attention to semiology, and a simple bedside glucose measurement ultimately uncovered the correct diagnosis. Clinicians should be mindful of diagnostic inertia, especially in atypical or treatment-resistant seizures. This case highlights the utility of home video recordings, the need to investigate metabolic causes, and the potential curability of insulinoma with early surgical intervention.

References

1. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-1077.
2. Sultana B, Panzini MA, Veilleux Carpentier A, et al. Incidence and prevalence of drug-resistant epilepsy: a systematic review and meta-analysis. Neurology. 2021;96(17):805-817.
3. Gesche J, Cornwall CD, Delcomyn L, Rubboli G, Beier CP. Pseudoresistance in idiopathic/genetic generalized epilepsies – Definitions, risk factors, and outcome. Epilepsy Behav. 2022;130:108633.
4. Benbadis S. The differential diagnosis of epilepsy: A critical review. Epilepsy Behav. 2009;15(1):15-21.
5. Murakami T, Yamashita T, Yabe D, et al. Insulinoma with a history of epilepsy: still a possible misleading factor in the early diagnosis of insulinoma. Intern Med. 2017;56(23):3199-3204.
6. Desimone ME, Weinstock RS. Hypoglycemia. In: Feingold KR, Ahmed SF, Anawalt B, et al., eds. Endotext. MDText.com, Inc.; 2000. http://www.ncbi.nlm.nih.gov/books/NBK279137/ Accessed 14 Sep 2025.
7. Liu S, Yu W, Lü Y. The causes of new-onset epilepsy and seizures in the elderly. Neuropsychiatr Dis Treat. 2016;12:1425-1434.
8. Karakas C, Ferreira LD, Haneef Z. Use of video alone for differentiation of epileptic seizures from non-epileptic spells: A systematic review and meta-analysis. Seizure. 2023;110:177-187.
9. Dudley A, Khalil MI, Mullins G, et al. Hypoglycaemic events resembling focal seizures -A case report and literature review. Seizure. 2022;94:10-17.
10. Blaabjerg L, Juhl CB. Hypoglycemia-induced changes in the electroencephalogram: an overview. J Diabetes Sci Technol. 2016;10:1259-67.
11. Topsakal Ş, Yaylalı GF, Yarar Z, et al. Multicenter study on the clinical characteristics, diagnosis, and treatment outcomes of insulinoma: insights from 15 medical centres. Clin Endocrinol. 2025;103(1):57-65.
12. Maggio I, Mollica V, Brighi N, et al. The functioning side of the pancreas: a review on insulinomas. J Endocrinol Invest. 2020;43(2):139-48.
13. LaFrance WC, Baker GA, Duncan R, et al. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach: A report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005-2018.