Risk factors for drug-resistant epilepsy according to sex: a cohort study conducted in a middle-income country

Lagger, Ignacio; Pacha, Sol; Garino, Eliana; Martinez, Oscar; Knorre, Eduardo; Ernst, Glenda

doi:10.1055/s-0046-1827051

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Original Article • Arq. Neuro-Psiquiatr. 84 (7) • 2026 • https://doi.org/10.1055/s-0046-1827051 linkcopy

Risk factors for drug-resistant epilepsy according to sex: a cohort study conducted in a middle-income country

SCIMAGO INSTITUTIONS RANKINGS

Background Drug-resistant epilepsy (DRE) affects 30% of patients with epilepsy. Although multiple risk factors (RFs) are recognized, there are few studies that explore the differences in clinical presentation, etiology and RFs considering the sex, especially in Latin America.

Objective To analyze sex differences in clinical features, outcomes and RFs for DRE in patients enrolled in 2 hospitals of Buenos Aires between 2020 and 2022.

Methods Multicenter retrospective cohort study. Clinical variables, epilepsy characteristics, and complementary studies of patients over 18 years with epilepsy were collected. Descriptive analyses, bivariate comparisons (Chi-squared, t-test/Mann-Whitney U test) and logistic regressions were applied to adjust for confounding factors.

Results A total of 122 patients were included, of whom 44 had DRE. The prevalence of DRE was slightly higher in men than in women (39.6 vs. 33.3%). Male sex showed 4 RFs for DRE: personal history (odds ratio [OR]: 7.82; 95%CI: 1.54–39.51), magnetic resonance imaging (MRI) with abnormal findings (OR: 4.40; 95%CI: 1.26–15.41), symptomatic etiology (OR: 4.77; 95%CI: 1.44–15.77), and time of evolution (OR: 1.05; 95%CI: 1.00–1.06). In women, time of evolution was the only RF for DRE (OR: 1.04; 95%CI: 1.00–1.08).

Conclusion There are sex differences in clinical, etiological, and imaging features of DRE. It is important to incorporate a sex perspective into the initial assessment, as this could contribute to the early identification of patients with higher risk of DRE. Particularly in men with clinical factors associated with higher risk, it would be advisable to implement earlier and more intensive follow-up strategies.

Keywords
Drug Resistant Epilepsy; Sex; Risk Factors; Epilepsy; Seizures

Patients' characteristics (n = 122)		Drug-resistant epilepsy	Nondrug-resistant epilepsy	p-value
Total (n)		44	78
Age (years): median (interquartile range 25–75)		43 (34.25–53.5)	41 (31.75–53)	0.99
Male sex: n (%)		21 (47.72)	32 (41.02)	0.56
Personal history: n (%)		42	74
Risk factor				0.55
	1 or more	27	43
	0	15	31
Traumatic brain injury		6 (13.63)	11 (14.28)	0.9
Meningitis		0 (0)	4 (5.19)	0.295
Febrile seizure		9 (20.45)	2 (2.59)	0.0018
Drugs		1 (2.27)	0 (0)	0.36
Family history		7 (15.90)	19 (24.67)	0.35
Others		13 (29.54)	21 (27.27)	0.83
Time of evolution (years): median (interquartile range 25–75)		22 (14.5–39)	16 (7–24)	0.0041
Epilepsy type: n (%)		44	78
Generalized		16 (36.36)	42 (53.84)	0.08
Focal		28 (63.63)	34 (43.58)	0.039
Unknown		0 (0)	2 (2.56)	0.53
Location of epileptogenic zone: n (%)		44	78
Frontal		4 (9.09)	7 (8.97)	0.9
Temporal		17 (38.63)	17 (21.79)	0.059
Parietal		1 (2.27)	1 (1.28)	0.9
Occipital		0 (0)	2 (2.56)	0.53
Insular		1 (2.27)	1 (1.28)	0.9
Mesial		9 (20.45)	0 (0)	0.0001
Undetermined		21 (47.72)	50 (64.10)	0.08
Seizure type: n (%)		44	78
Generalized		17 (38.63)	47 (60.25)	0.0591
Focal impaired awareness		24 (54.54)	27 (34.61)	0.0371
Focal aware		3 (6.81)	4 (5.12)	0.7
Unknown		0 (0)	0 (0)	0.9
Neuroimaging: n (%)
Magnetic resonance imaging (n = 107)		42	65
	Abnormal	26 (61.90)	23 (35.38)	0.0098
	Normal	16 (38.09)	42 (64.61)	0.0098
Computed tomography (n = 38)		11	27	0.71
	Abnormal	4 (36.36)	8 (29.62)
	Normal	7 (63.63)	19 (70.37)
Electroencephalogram: n (%)		40	70
	Abnormal	31 (77.5)	47 (67.15)	0.28
	Normal	9 (22.5)	23 (32.85)	0.28
Etiology, n (%)		44	78
Symptomatic		25 (56.81)	28 (35.89)	0.036
Idiopathic/Undetermined		19 (43.18)	50 (64.10)	0.036

Patients' characteristics (men = 53)		Drug-resistant epilepsy	Nondrug-resistant epilepsy	p-value
Total: n (%)		21 (39.62)	32 (60.37)
Age (years): median (interquartile range 25–75)		43 (32–57)	40.5 (29.25–51.25)	0.96
Personal history: n (%)		22	28
Risk factor				0.016
	1 or more	19 (83.36)	15 (53.57)
	0	3 (13.63)	13 (46.42)
Traumatic brain injury		5 (22.72)	6 (21.42)	0.73
Meningitis		0 (0)	2 (7.14)	0.5
Febrile seizure		4 (18.18)	2 (7.14)	0.2
Drugs		1 (4.54)	0 (0)	0.4
Family history		4 (18.18)	8 (28.57)	0.74
Others		9 (40.90)	8 (28.57)	0.23
Time of evolution (years): median (interquartile range 25–75)		22 (13.25–31.5)	15 (3–24)	0.04
Epilepsy type: n (%)		21	32
Generalized		7 (33.33)	17 (53.12)	0.17
Focal		14 (66.66)	14 (43.75)	0.15
Unknown		0 (0)	1 (3.12)	0.9
Location of epileptogenic zone:n (%)		21	32
Frontal		2 (9.52)	3 (9.37)	0.9
Temporal		8 (38.09)	8 (25)	0.36
Parietal		1 (4.76)	0 (0)	0.39
Occipital		0 (0)	0 (0)	0.9
Insular		0 (0)	0 (0)	0.9
Mesial		3 (14.28)	0 (0)	0.056
Undetermined		10 (47.61)	21 (65.62)	0.25
Seizure type: n (%)		21	32
Generalized		8 (38.09)	19 (59.37)	0.16
Focal impaired awareness		12 (57.14)	12 (37.5)	0.16
Focal aware		1 (4.76)	1 (3.12)	0.9
Neuroimaging: n (%)
Magnetic resonance imaging (n = 46)		20	26
	Abnormal	14 (70)	9 (34.61)	0.18
	Normal	6 (30)	17 (65.38)	0.18
Computed tomography (n = 16)		6	10
	Abnormal	4 (66.66)	2 (20)	0.11
	Normal	2 (33.33)	8 (80)	0.11
Electroencephalogram: n (%)		18	30
	Abnormal	13 (72.22)	21 (70)	0.9
	Normal	5 (27.77)	9 (30)	0.9
Etiology: n (%)		21	32
Symptomatic		15 (71.42)	11 (34.37)	0.011
Idiopathic/Undetermined		6 (28.57)	21 (65.62)	0.011

Patients' characteristics(women = 69)		Drug-resistant epilepsy	Nondrug-resistant epilepsy	p-value
Number of patients (%)		23 (33.33)	46 (66.66)
Age (years): median (interquartile range 25–75)		43 (32–57)	43 (35.75–53)	0.9
Personal history: n (%)		20	46
Risk factor				0.17
	1 or more	8 (40)	28 (60.86)	0.17
	0	12 (60)	18 (39.13)
Traumatic brain injury		1 (5)	5 (10.86)	0.65
Meningitis		0 (0)	2 (4.34)	0.54
Febrile seizure		5 (25)	0 (0)	0.003
Drugs		0 (0)	0 (0)	0.9
Family history		3 (15)	11 (23.91)	0.35
Others		4 (20)	13 (28.26)	0.38
Time of evolution (years): median (interquartile range 25–75)		28 (14–40)	16 (8–27.5)	0.028
Epilepsy type: n (%)		23	46
Generalized		9 (39.16)	26 (56.52)	0.2
Focal		14 (60.86)	20 (43.47)	0.2
Unknown		0 (0)	0 (0)	0.9
Location of epileptogenic zone: n (%)		23	46
Frontal		2 (8.69)	4 (8.69)	0.9
Temporal		9 (39.13)	9 (19.56)	0.09
Parietal		0 (0)	1 (2.17)	0.9
Occipital		0 (0)	2 (4.34)	0.54
Insular		1 (4.34)	1 (2.17)	0.9
Mesial		6 (26.08)	0 (0)	0.0008
Undetermined		11 (47.28)	29 (63.04)	0.3
Seizure type: n (%)		23	46
Generalized		9 (39.13)	28 (50)	0.12
Focal impaired awareness		12 (52.17)	15 (32.60)	0.12
Focal aware		2 (8.69)	3 (6.52)	0.9
Neuroimaging: n (%)
Magnetic resonance imaging (n = 61)		22	39
	Abnormal	12 (54.54)	14 (35.98)	0.18
	Normal	10 (45.45)	25 (64.10)	0.18
Computed tomography (n = 22)		5	17
	Abnormal	0 (0)	6 (35.29)	0.26
	Normal	5 (100)	11 (64.70)	0.26
Electroencephalogram (n = 62)		22	40
	Abnormal	18 (81.81)	26 (65)	0.24
	Normal	4 (18.18)	14 (35)	0.24
Etiology n (%)		23	46
Symptomatic		10 (43.47)	17 (36.95)	0.61
Idiopathic/Undetermined		13 (56.52)	29 (63.04)	0.61

Variable		Odds ratio	95%CI
Male sex
	Time of evolution (years)	1.05	1.00–1.106
	Personal history	7.82	1.54–39.51
	Abnormal magnetic resonance imaging scan	4.40	1.26–15.41
	Symptomatic etiology	4.77	1.44–15.77
Female sex
	Time of evolution (years)	1.04	1.00–1.08

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[TFN1] Note: Other risk factors include CNS infections, pregnancy complications, and birth complications. The p-values in bold indicate statistical significance (p < 0.05).