Clinical, Neuroimaging, and Electroencephalographic Spectrum of Patients with Isolated Nocturnal Seizures: An Experience at a Tertiary Care Center

Keywords

epilepsy - sleep - EEG

Introduction

Sleep and epilepsy share a complicated interrelationship with each other. Nocturnal seizures (NS) can significantly distort the sleep architecture and can have a grave impact on the quality of life and performance of the patient. On the other hand, poor sleep quality can affect seizure control despite adequate medical management.[1] Use of several antiseizure medications (ASMs) affects the patterns of normal sleep architecture causing increase daytime somnolence and cognitive impairment.[2] This leads to poor quality of life and vicious cycle of impaired seizure control.

The International League Against Epilepsy (ILAE) defines NS as seizures occurring exclusively or predominantly (more than 90%) in sleep.[3] NS are difficult to diagnose and treat due to their time of occurrence, which may be frequently missed. Some of the NS are overlooked or misdiagnosed as various periodic sleep disorders or parasomnias.[4] Hence, it is essential to keep a narrow index of suspicion while evaluating cases of nocturnal paroxysmal events. Very few studies are available in the Indian context describing the clinical spectrum and possible etiology of isolated purely NS. Due to lack of infrastructure for dedicated sleep laboratories and facilities for prolonged night time video electroencephalogram (VEEG) recordings even in many tertiary health care centers further limits the scope of research. Our study describes the demographic, clinical, neuroimaging, and EEG profile of patients with isolated NS. This will provide an insight into the diagnosis and evaluation of NS, which may also help in the development of devices for nocturnal supervision, which will help in the better characterization of sleep-associated motor events.

Methods

Aims and Objectives

• (1) To study the demographic and clinical profile of patients with isolated NS.

• (2) To analyze the neuroimaging and EEG features of patients with isolated NS.

Study Design and Sample Recruitment

This is a prospective cohort study conducted at the outpatient (OPD) and inpatient settings of the department of neurology at a tertiary care hospital in South India after approval from the institutional ethics committee. Consecutive sampling technique was used and we recruited the patients during study period from June 2017 till June 2021 who were diagnosed to have pure sleep-associated seizures. Written informed consent was obtained from all the study participants.

Inclusion Criteria

• (1) All patients with exclusive sleep-associated seizures

• (2) Age group between 5 and 80 years

Exclusion Criteria

• (1) Patients with both wake and sleep-related seizures

• (2) Patients already diagnosed with nonepileptic periodic sleep disorders

• (3) Patients with past history of dissociative disorders and psychiatric illnesses

• (4) Drug-related or alcohol withdrawal seizures

Methodology

Demographic details and clinical history were recorded and entered in predesigned pro forma. Patients and patients' attenders were interviewed and available video recordings were observed to specify seizure semiology. Seizures were classified as per the current ILAE 2017 classification system and those with unwitnessed onset were classified under the category of unknown onset. Thorough neurological examination was performed in all patients. We divided our patients into two groups—patients having seizure episodes from onset of sleep (approximately around 11 p.m.) till 3 a.m. and those having seizure attacks from 3 a.m. till 6 a.m. Clinical parameters associated with seizures such as tongue bite, bowel and bladder incontinence, and shoulder dislocation were noted as well. All patients were evaluated with 1.5 or 3 Tesla magnetic resonance imaging (MRI) with epilepsy protocol unless there was an absolute contraindication in which case computed tomography (CT) brain was performed. Sixteen-channel awake and sleep EEG was performed in all patients for a minimum duration of 60 minutes. Eight-hour prolonged VEEG was performed in 15 patients. The drug regimen was carefully noted in terms of which drugs were used, the duration of each drug received, and whether the patients were well controlled on monotherapy or required two or more ASMs. Patients were followed at 3 monthly intervals for a minimum duration of 12 months and assessed for their seizure status at the last follow-up either via OPD visits or telephonic conversations.

Statistical Analysis

Data was expressed as mean and standard deviation in a case of normal distribution and median with 25th and 75th percentile for nonnormal distribution. Data was expressed in number with percentages for the categorical variables. Continuous variables were compared using t-test and chi-square or Fischer's exact test was applied for categorical variables. A p-value of less than 0.05 was considered statistically significant. All the analyses were performed using SPSS version 25.0.

Results

The mean age of the patients in the study was 31.79 ± 14.6 years. The mean age at the onset of seizures was 25.9 ± 16.41 years. The male-to-female ratio was 4:3. Majority of the patients (68.5%) had seizures from 11 p.m. till 3 a.m. as compared to those who had seizures in the time frame of 3 a.m. to 6 a.m. (27.1%). Three patients had seizure attacks in both early and late night hours, while seven patients additionally had seizure events during daytime naps as well. The demographic variables and clinical details of the seizures are depicted in [Table 1].

Table 1 Demographic and seizure characteristics of the study participants (n = 70)

Parameters	Frequency (%)
Age at the onset of seizures (y, mean ± SD)	25.9 ± 16.41
Gender
Male	41 (58.57)
Female	29 (41.42)
Time of seizure occurrence
Early night time seizures (11 p.m.–3 a.m.)	48 (68.57)
Late night time seizures (3 a.m.–6 a.m.)	19 (27.14)
Both early and late night hours	3 (4.28)
Seizure events in daytime naps	7 (10)
Seizure types
Generalized	45 (64.28)
Focal	20 (28.57)
Unknown onset	10 (14.28)
Clinical parameters associated with seizures
Tongue bite	37 (52.85)
Urinary/Bowel incontinence	14 (20)
Fall from the bed	10 (14.28)
Shoulder dislocation	3 (4.28)
Daytime somnolence	40 (57.14)
Febrile seizures	4 (5.71)
Perinatal insult	3 (4.28)
Family history of epilepsy	8 (11.42)
Response at last follow-up
Seizure free on monotherapy	46 (65.71)
Seizure free on two antiseizure drugs	16 (22.85)
Requiring more than two drugs	3 (4.28)
Not seizure free at last follow-up	3 (4.28)
Status unknown	2 (2.85)

Abbreviation: SD, standard deviation.

Among all the witnessed episodes, generalized seizures were the most commonly observed seizure semiology (64%) where the onset was clear. However, in 10 patients the onset was never witnessed and was only realized after the ictal cry or sounds or fall from the bed. Clinical parameters associated with the seizure attacks were assessed. We observed that among these, daytime somnolence was the most commonly reported symptom (57.1%) by the patients the very next day. Eight patients (11.4%) had a positive family history of epilepsy including two patients who had self-limited epilepsy with centrotemporal spikes (SeLECTS) and four patients had history of sleep-related hypermotor epilepsy (SHE). Out of four patients who had history of febrile seizures, two had mesial temporal sclerosis (MTS) on neuroimaging.

Majority of the patients had normal regular 60 minutes awake and sleep EEG record (81.42%). Focal abnormality was found more frequently than generalized epileptiform discharges. Two children were diagnosed with SeLECTS correlating with EEG findings. Two patients with family history of SHE had focal epileptiform discharges arising from frontal chain of electrodes, while the other two had normal findings. Overnight VEEG was performed in 15 patients, which showed focal discharges more commonly than that of generalized abnormalities. The EEG findings are enumerated in [Table 2].

Table 2 EEG and neuroimaging findings of the study participants (n = 70)

Parameters	Frequency (%)
Routine EEG (awake and sleep)	n = 70
Normal	57 (81.42)
Generalized	3 (4.28)
Focal	10 (14.28)
VEEG	n = 15
Normal	9 (60)
Generalized	2 (13.33)
Focal	4 (26.66)
MRI (lesion locations)	n = 63
Normal	39 (61.90)
Frontal	10 (15.87)
Parietal	4 (6.34)
Temporal	3 (4.76)
Multi-lobar	7 (11.11)
CT scan	n = 7
Normal	5 (71.42)
Abnormal (frontal)	2 (28.57)
Hemispheric distribution of lesions	n = 26
Left	13 (50)
Right	10 (38.46)
Bilateral	3 (11.53)

Abbreviations: CT, computed tomography; EEG, electroencephalogram; MRI, magnetic resonance imaging; VEEG, video electroencephalogram.

MRI was performed in 63 patients out of which majority of the patients (61.9%) had normal findings. Calcified granulomas were the most common abnormal finding seen in seven patients followed by poststroke gliosis in five patients, MTS in three patients, and focal cortical dysplasia in three patients. Other findings noted were pachygyria, hypoxic insult, glioblastoma, and old intracranial hemorrhage in one patient each. The most common location of lesions was the frontal lobe (15.8%), and left-sided lesions were more common. Majority of these were calcified granulomas. CT imaging was performed in seven patients out of which two had calcified granulomas ([Table 2]). The comparison between the lesional and nonlesional cases in MRI studies has been depicted in [Table 3] ([Fig. 1], [Fig. 2]).

Table 3 Comparison of parameters between lesional and nonlesional MRI studies (n = 63)

Factors	Lesional cases (n = 24)	Nonlesional cases (n = 39)	p-Value
Age at onset (y, mean ± SD)	26.6 ± 12.2	26.3 ± 17.9	0.94
Gender			0.42
Male	16 (66.7)	22 (56.4)
Female	8 (33.3)	17 (43.6)
Time of seizure occurrence			0.89
Early night time	17 (70.8)	27 (69.2)
Late night time	7 (29.2)	12 (30.8)
Seizure semiology
Generalized	14 (58.3)	27 (69.2)	0.38
Focal	7 (29.2)	11 (28.2)	0.93
Unknown	4 (16.7)	5 (12.8)	0.67
Clinical parameters
Tongue bite	9 (37.5)	24 (61.5)	0.06
Bladder and bowel incontinence	4 (16.7)	9 (23.1)	0.54
Fall from bed	6 (25.0)	4 (10.3)	0.12
Shoulder dislocation	3 (12.5)	0 (0.00)	0.05
Daytime somnolence	11 (45.8)	23 (59.0)	0.31
Head injury	0 (0.0)	1 (2.6)	1.00
Febrile seizures	1 (4.2)	2 (5.1)	1.00
Perinatal insult	0 (0.0)	2 (5.1)	0.52
Family history of epilepsy	2 (8.3)	5 (12.8)	0.58
EEG (routine)			0.05
Normal	17 (70.8)	35 (89.7)
Abnormal	7 (29.2)	4 (10.3)

Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance imaging; SD, standard deviation.

The comparison between early night time and late night time seizures did not establish any significant statistical correlation in terms of various seizure parameters. Also, no significant correlation was found on the comparison of EEG and neuroimaging findings in both the time frames ([Table 4]).

Table 4 Comparison of parameters between early night time seizures (11 p.m.–3 a.m.) and late night time seizures (3 a.m.–6 a.m.)

Factors	Early night time seizures (n = 51)	Late night time seizures (n = 19)	p-Value
Age of the study participants (y, mean ± SD)	30.6 ± 14.8	34.9 ± 14.2	0.28
Age of onset of seizures (y, mean ± SD)	25.0 ± 16.9	28.5 ± 15.1	0.44
≤ 18	22 (43.1)	7 (36.8)
19–30	12 (23.5)	4 (21.1)
> 30	17 (33.3)	8 (42.1)
Gender			0.94
Male	30 (58.8)	11 (57.9)
Female	21 (41.2)	8 (42.1)
Seizure semiology
Generalized	32 (62.7)	13(68.4)	0.66
Focal	16 (31.4)	4 (21.1)	0.40
Unknown	7 (13.7)	3 (15.8)	0.82
Clinical parameters
Tongue bite	26(51.0)	11 (57.9)	0.61
Bladder and bowel incontinence	9 (17.6)	5 (26.3)	0.42
Fall from bed	9 (17.6)	1 (5.3)	0.19
Shoulder dislocation	2 (3.9)	1 (5.3)	1.00
Daytime somnolence	30 (58.8)	10 (52.6)	0.64
Head injury	0 (00.0)	1 (5.3)	0.27
Febrile seizures	4 (7.8)	0 (0.0)	0.57
Perinatal insult	2 (3.9)	1 (5.3)	1.00
Family history of epilepsy	5 (9.8)	3 (15.8)	0.48
EEG (routine)
Normal	39 (76.4)	18 (94.7)	0.08
Generalized	3 (5.8)	0 (0.0)	0.27
Focal	9 (17.64)	1 (5.3)	0.18
MRI (n = 63)
Lesional	17 (33.3)	7 (36.8)	0.89
Nonlesional	27 (52.9)	12(63.1)
Left-sided lesions	8 (15.6)	5 (26.3)	0.36
Right-sided lesions	7 (13.7)	2 (10.5)

Abbreviations: EEG, electroencephalogram; MRI, magnetic resonance imaging; SD, standard deviation.

Levetiracetam (LEV) was the most commonly prescribed drug (48.5%) both as a monotherapy and as a part of multidrug regimen in our study followed by oxcarbazepine (22.8%). Other drugs prescribed were phenytoin (7%), sodium valproate (4.2%), clobazam (2.8%), carbamazepine (2.8%), phenobarbitone (2.8%), and lacosamide (1.4%). Clobazam was the most common second add-on drug (18.5%) followed by lacosamide (4.2%). Complete seizure control was achieved in nearly 65% of the patients on monotherapy. Overall, there was a good outcome in terms of seizure control. The response to therapy has been depicted in [Table 1].

Discussion

The relationship between sleep and focal syndromic epilepsies have been analyzed over the past few years. However, very few studies are available shedding a light on pure sleep-associated seizures especially the symptomatic seizures. Our study compares various seizure parameters and their relation to the sleep stages and overall clinical outcome.

Sleep-associated seizures are commonly observed in the younger age group of patients but the range may vary widely. Our study showed the age of onset of seizures in mid-twenties, which is similar to the study by Provini et al assessing SHE previously known as nocturnal frontal lobe epilepsy.[5] Indian study by Goel et al comparing sleep and wake seizures also noted that most of the patients with sleep-associated epilepsy had their onset before twenties.[6] Clinically, well-known nocturnal epilepsy syndromes like SeLECTS and Landau–Kleffner syndrome, which are a subtype of epileptic encephalopathy with spike and wave activation in sleep (EE-SWAS), are predominantly childhood onset epilepsies. However, these epilepsy syndromes tend to improve completely or partially over a period of time and hence their incidence seems to be lower in the adult population.[7] [8] We observed male predominance in our study. SHE syndromes have male predominance running in families, the underlying cause of which is not clear.[5] [9]

Sleep-related seizures are easy to go unnoticed. The average duration of witnessed attacks in our study was 2.5 minutes. Even though the attacks are actually witnessed, the exact nature of the ictal onset may be misinterpreted. This could be because of the late arousal of bed partner following ictal cry or limb movements well after the onset of premonitory aura occurring during sleep. Studies on nocturnal frontal lobe seizures have proven to be a good model for different motor events lasting briefly.[5] [10] Many of them may mimic parasomnias especially when they present with dystonic-dyskinetic and ballic type of movements during seizure episodes.[4] [11] The most common seizure semiology reported in our study was generalized seizures. This is similar to the study by Gibberd and Bateson who reported 77.8% patients with sleep-related seizures having generalized motor semiology.[12] However, there is a clinical possibility that patients during sleep may not be aware of the focal aura or experiential phenomenon, which they are able to describe during wake seizures. Hence, many focal seizures with secondary generalization may be mistaken as primarily GTCs. This highlights the importance of EEG in both awake and sleep state in all NS cases to have more information about the focality. This may have a prognostic implication. As per the study by Park et al, seizure control outcome was relatively poor and the development of new wake seizures was frequent in patients with recurrent sleep-related focal seizures as compared to generalized seizures.[13] Also, correct seizure typing helps in tailoring the treatment as some drugs given for focal seizures may worsen certain genetic generalized epilepsy syndromes.[14]

Daytime somnolence was reported in more than half of patients the very next day. Considerable literature from the western world sheds the light on the adverse impact of epilepsy on sleep and overall quality of life leading to significant psychosocial stress.[15] Bazil reported that NS is not a benign entity and the resulting sleep disruption can cause lack of concentration and daytime somnolence.[16] These observations are in contrast to the study by Ekizoglu et al who concluded that sleep-associated seizures had a good prognosis and did not seem to affect the sleep quality.[17]

Sleep stages and occurrence of epileptic discharges have been known to have a close association. Interictal epileptiform discharges (IEDs) and seizures are predominantly activated in stage 2 and 3 of non-rapid eye movement (NREM) sleep whereas rapid eye movement (REM) sleep being a relatively protective sleep.[18] [19] The early night hours are predominantly constituted of NREM sleep and there is a higher probability of seizure occurrence during this phase.[20] Sleep spindles, slow oscillations, and high-frequency oscillations (HFOs) during NREM sleep provide neurobiological scaffold for memory consolidation. HFO is an emerging new biomarker for identifying the epileptic zone during planning of epilepsy surgeries.[21] These HFOs are noted at highest rate in NREM contributing to its unstable nature. Our study showed that nearly two-thirds of patients had seizure attacks within early night hours (11 p.m.–3 a.m.). Also, patients with seizures in both early as well as late night hours had most of their attacks in initial part of their sleep. These observations, however, did not show any statistical correlation between the seizure burden and focality in our study; though it is reported in the literature that NREM activates generalized IED more than that of focal IEDs.[18] [19] Seizures occurring in daytime sleep as well consolidates the interrelationship between sleep and epilepsy and sleep as a trigger for the occurrence of seizures.[22] [23] However, this may not always be the case and some patients may develop seizures in wakefulness later in the course.[13]

Nearly 80% of our patients had normal awake and sleep record. The proportion of abnormal EEG findings vary widely across different studies, though most of the studies report abnormal findings in nearly half of the cases on either conventional or VEEG recordings.[6] [24] [25] Inadequate sleep deprivation prior to EEG, patients already loaded with ASM prior to routine EEG, and limited patients undergoing overnight VEEG because of logistic issues could be some of the reasons of high proportion of overall normal EEG findings in our study. Limited literature is available on the EEG data in symptomatic NS especially in the Indian context.[6] Majority of the studies from the past were conducted for familial epilepsy syndromes like SHE, nocturnal temporal epilepsy syndrome, and EE-SWAS.[5] [8] [9] High index of clinical suspicion, overnight VEEG recordings, and polygraphic study in certain cases may help in better characterization of NS as well as to differentiate it from parasomnias as the sensitivity of VEEG outweighs that of routine records.[26] [27]

Our study showed abnormal neuroimaging findings in slightly over one-third of patients, which is less as compared to the study by Goel et al, which reported imaging abnormalities in nearly half of their patients.[6] Similar to this study, we reported calcified granulomas as the most common etiology and the frontal lobe was the most commonly involved lobe with left-sided lesions observed frequently than right. An animal study has supported the theory that NREM sleep is left hemispheric dominant and REM being the right dominant.[28] This hypothetical correlation can explain the association of NS with left-sided lesions. As per the literature, neuroimaging is either normal or may be noncontributory in the majority of cases of nocturnal genetic epilepsy syndromes.[5] [29] However, sparse literature is available on neuroimaging findings of symptomatic NS. Since focal symptomatic seizures are the second most common type of seizures described worldwide, more studies are required for better characterization of NS with symptomatic etiology.[30]

Study by Fernández and Salas-Puig noted that a good seizure control was possible with a single drug for nonlesional epilepsies.[31] Few more studies supported this fact that adequate seizure control can be achieved in NS with monotherapy alone similar to the observation from our study.[30] [32] [33] LEV was the most preferred drug in our patients due to its better side-effect profile, broad-spectrum antiepileptic action, relative safety in younger reproductive age group, and has a minimal effect on the sleep structure.[2] Carbamazepine is the preferred ASM for monotherapy in most of the previous studies on SHE and nocturnal temporal lobe epilepsy probably because of the focal nature of seizures and its good clinical outcome in older literature.[10] Clobazam was the preferred second add-on drug due to its additional benefit on disturbed sleep and bedtime dosing. However, benzodiazepines (BZDs) are not preferred drugs for chronic treatment of epilepsy due to their detrimental effect on sleep architecture by significantly reducing REM and slow wave sleep.[2]

The main limitation of our study was fewer number of patients undergoing VEEG due to logistic reasons. Hence, the comparison between early night hour and late night hour seizure groups has methodological limitations. As this was not confirmed by video telemetry, there is a possibility of ascertainment bias. Due to lack of long-term follow-up, we could not assess the risk of wake seizures later during the lifetime. We lacked a comparison group of patients with seizures in wake state to study the association between various seizure parameters. Not all patients underwent 3 Tesla MRI epilepsy protocol due to cost factors and unavailability of this facility in past years at our institution. Despite these limitations, our work may pave a way for more comparative studies on all kinds of NS as previous literature was predominantly focused on syndromic sleep-associated epilepsies. This will help in better understanding and management of this unique entity.

Conclusion

NS are difficult to diagnose requiring a high index of clinical suspicion. Routine awake and sleep EEG recording may not be sufficient for proper characterization of NS and overnight VEEG recording is required in most of the cases. Involvement of the frontal lobe and left-sided lesions can have a role in the etiopathogenesis of NS, though more studies are required to consolidate this theory. Majority of NS show good treatment response on monotherapy and thus early detection as well as adequate treatment can have a good functional outcome as NS can cause significant distortion of the sleep architecture and worsening of the quality of life.

Fig. 1 An 11-year-old male patient with history of perinatal insult presented with right focal seizures during sleep. Magnetic resonance imaging (MRI) T2 fluid-attenuated inversion recovery (FLAIR) sequence (A) showed area of gliosis and volume loss in the left anterior part of the middle frontal gyrus with hemosiderin deposition on susceptibility-weighted angiography (SWAN) sequences (B) suggestive of remote vascular insult. Electroencephalogram (EEG) (C, D) suggestive of epileptiform discharges from bilateral frontal chain of electrodes.

Fig. 2 A 24-year-old female patient with a history of four episodes of left focal seizures with secondary generalization during sleep. Magnetic resonance imaging (MRI) susceptibility-weighted angiography (SWAN) sequence (A) showed a calcified granuloma in the right precentral gyrus. Corresponding T2 fluid-attenuated inversion recovery (FLAIR) sequence (B) showed perilesional edema. Electroencephalogram (EEG) (C, D) showed epileptiform activity over the right inferior frontal and mid-temporal regions.

• References

• 1 Tan B, Liu Q, Qin Y. et al. Insomnia in epilepsy is associated with nocturnal seizures and anxiety. Epilepsy Behav 2024; 150: 109559
• 2 Bazil CW. Nocturnal seizures and the effects of anticonvulsants on sleep. Curr Neurol Neurosci Rep 2008; 8 (02) 149-154
• 3 Berry RB. Chapter 27 - Clinical electroencephalography and nocturnal epilepsy. In: Berry RB. ed. Fundamentals of Sleep Medicine. Saint Louis: W.B. Saunders; 2012: 545-566
• 4 Henning O, Markhus R, Dornish EEJ, Kostov KH, Heimisdottir F, Nakken KO. Strange episodes during sleep – epilepsy or parasomnia?. Tidsskr Den Nor Legeforening 2024 144. (04)
• 5 Provini F, Plazzi G, Tinuper P, Vandi S, Lugaresi E, Montagna P. Nocturnal frontal lobe epilepsy. A clinical and polygraphic overview of 100 consecutive cases. Brain 1999; 122 (Pt 6): 1017-1031
• 6 Goel D, Mittal M, Bansal KK, Srivastav RK, Singhal A. Sleep seizures versus wake seizures: a comparative hospital study on clinical, electroencephalographic and radiological profile. Neurol India 2008; 56 (02) 151-155
• 7 Nobili L, Proserpio P, Combi R. et al. Nocturnal frontal lobe epilepsy. Curr Neurol Neurosci Rep 2014; 14 (02) 424
• 8 Muzio MR, Cascella M, Al Khalili Y. Landau-Kleffner Syndrome. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2024
• 9 Bernasconi A, Andermann F, Cendes F, Dubeau F, Andermann E, Olivier A. Nocturnal temporal lobe epilepsy. Neurology 1998; 50 (06) 1772-1777
• 10 Scheffer IE, Bhatia KP, Lopes-Cendes I. et al. Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder. Brain 1995; 118 (Pt 1): 61-73
• 11 Derry C. Nocturnal frontal lobe epilepsy vs parasomnias. Curr Treat Options Neurol 2012; 14 (05) 451-463
• 12 Gibberd FB, Bateson MC. Sleep epilepsy: its pattern and prognosis. BMJ 1974; 2 (5916) 403-405
• 13 Park SA, Lee BI, Park SC. et al. Clinical courses of pure sleep epilepsies. Seizure 1998; 7 (05) 369-377
• 14 Rathore C, Patel KY, Satishchandra P. Current concepts in the management of idiopathic generalized epilepsies. Ann Indian Acad Neurol 2022; 25 (01) 35-42
• 15 Strine TW, Kobau R, Chapman DP, Thurman DJ, Price P, Balluz LS. Psychological distress, comorbidities, and health behaviors among U.S. adults with seizures: results from the 2002 National Health Interview Survey. Epilepsia 2005; 46 (07) 1133-1139
• 16 Bazil CW. Nocturnal seizures. Semin Neurol 2004; 24 (03) 293-300
• 17 Ekizoglu E, Baykan B, Bebek N, Gurses C, Gokyigit A. Sleep characteristics of patients with epilepsy with pure sleep-related seizures. Epilepsy Behav 2011; 21 (01) 71-75
• 18 Grigg-Damberger M, Foldvary-Schaefer N. Bidirectional relationships of sleep and epilepsy in adults with epilepsy. Epilepsy Behav 2021; 116: 107735
• 19 Ng M, Pavlova M. Why are seizures rare in rapid eye movement sleep? Review of the frequency of seizures in different sleep stages. Epilepsy Res Treat 2013; 2013: 932790
• 20 Bazil CW, Walczak TS. Effects of sleep and sleep stage on epileptic and nonepileptic seizures. Epilepsia 1997; 38 (01) 56-62
• 21 Frauscher B, Gotman J. Sleep, oscillations, interictal discharges, and seizures in human focal epilepsy. Neurobiol Dis 2019; 127: 545-553
• 22 Crespel A, Coubes P, Baldy-Moulinier M. Sleep influence on seizures and epilepsy effects on sleep in partial frontal and temporal lobe epilepsies. Clin Neurophysiol 2000; 111 (Suppl. 02) S54-S59
• 23 Çilliler AE, Güven B. Sleep quality and related clinical features in patients with epilepsy: a preliminary report. Epilepsy Behav 2020; 102: 106661
• 24 Giuliano L, Uccello D, Fatuzzo D, Mainieri G, Zappia M, Sofia V. Electroclinical findings of minor motor events during sleep in temporal lobe epilepsy. Epilepsia 2017; 58 (07) 1261-1267
• 25 Provini F, Plazzi G, Montagna P, Lugaresi E. The wide clinical spectrum of nocturnal frontal lobe epilepsy. Sleep Med Rev 2000; 4 (04) 375-386
• 26 Bialasiewicz P, Nowak D. Obstructive sleep apnea syndrome and nocturnal epilepsy with tonic seizures. Epileptic Disord 2009; 11 (04) 320-323
• 27 Boursoulian LJ, Schenck CH, Mahowald MW, Lagrange AH. Differentiating parasomnias from nocturnal seizures. J Clin Sleep Med 2012; 8 (01) 108-112
• 28 Vyazovskiy VV, Borbély AA, Tobler I. Interhemispheric sleep EEG asymmetry in the rat is enhanced by sleep deprivation. J Neurophysiol 2002; 88 (05) 2280-2286
• 29 Ryvlin P, Rheims S, Risse G. Nocturnal frontal lobe epilepsy. Epilepsia 2006; 47 (Suppl. 02) 83-86
• 30 Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020; 54 (02) 185-191
• 31 Fernández LB, Salas-Puig J. Pure sleep seizures: risk of seizures while awake. Epileptic Disord 2007; 9 (01) 65-70
• 32 Yaqub BA, Waheed G, Kabiraj MM. Nocturnal epilepsies in adults. Seizure 1997; 6 (02) 145-149
• 33 Guilhoto LMFF, Loddenkemper T, Vendrame M, Bergin A, Bourgeois BF, Kothare SV. Higher evening antiepileptic drug dose for nocturnal and early-morning seizures. Epilepsy Behav 2011; 20 (02) 334-337