Nocturnal Frontal Lobe Epilepsy Patients Research Articles

Comparative Approach to Detect Nocturnal Frontal Lobe Epilepsy Sleep Disorder through Frequency spectrum and its Energy Levels

EEG data has proved to reflect the activities of the brain over all the sections with respect to human activities. It is useful in both cases that are in awakening states and in the sleep stage. Most of brain disease is due to the deterioration of brain cells. In this research work, EEG data is used to generate some frequency-based energy level features for NFLE (Nocturnal Frontal Lobe Epilepsy) patients and normal persons. After experimentation, it is found that the percentage of energy levels may be considered as a parameter to distinguish healthily and defected EEG data due to sleep disorder. During this study, it is also found that S0 is proved to be helpful in the diagnosis of NFLE sleep disorder because in this stage the percentage energy level is to be high for alpha waves for patients having a sleep disorder. The results show that the average percentage energy level in NFLE patient is 0.009872 while in normal cases it is 0.0010148.

SCALING ANALYSIS OF THE A-PHASE DYNAMICS DURING SLEEP

In this work, the scaling behavior of the sleep process is evaluated by using detrended fluctuation analysis based on wavelets. The analysis is carried out from arrivals of short and recurrent cortical events called A-phases, which in turn build up the Cyclic Alternating Pattern phenomenon, and are classified in three types: A1, A2 and A3. In this study, 61 sleep recordings corresponding to healthy, nocturnal frontal lobe epilepsy patients and sleep-state misperception subjects, were analyzed. From the A-phase annotations, the onsets were extracted and a binary sequence with one second resolution was generated. An item in the sequence has a value of one if an A-phase onset occurs in the corresponding window, and a value of zero otherwise. In addition, we consider other different temporal resolutions from 2[Formula: see text]s to 256[Formula: see text]s. Furthermore, the same analysis was carried out for sequences obtained from the different types of A-phases and their combinations. The results of the numerical analysis showed a relationship between the time resolutions and the scaling exponents; specifically, for higher time resolutions a white noise behavior is observed, whereas for lower time resolutions a behavior towards to [Formula: see text]-noise is exhibited. Statistical differences among groups were observed by applying various wavelet functions from the Daubechies family and choosing the appropriate sequence of A-phase onsets. This scaling analysis allows the characterization of the free-scale dynamic of the sleep process that is specific for each sleep condition. The scaling exponent could be useful as a diagnosis parameter in clinics when sleep macrostructure does not offer enough information.

A clinical efficacy experience of Lacosamide on sleep quality in patients with Nocturnal Frontal Lobe Epilepsy (NFLE).

Background: Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy with seizures arising mainly during sleep and characterized by complex motor behavior or sustained dystonic posturing. First described in 1981, it was considered a motor disorder of sleep and was indicated as nocturnal paroxysmal dystonia (NPD). The debated on epileptic origin of this condition was demonstrated in 1990 and the term NFLE was introduced. Since then it has been demonstrated that the heterogeneous aspects of morpheic seizures were responsive to antiepileptic drugs (AED’s) with sodium blocking action mechanism, especially the carbamazepine (CBZ). Aim of Work and Methods: We report a clinical experience of NFLE patients associated with sleep disorders treated with Lacosamide, AED’s with a novel mechanism of action. In vitro electrophysiology studies have shown that lacosamide selectively boosts the slow inactivation of the sodium-voltage-dependent channels, resulting in a stabilization of the hypersensitive neuronal membranes. Results and Conclusion: On the treated patients we observed a positive clinical response to lacosamide therapy without significant side effects. In particular, the effective clinical response to the pharmacological treatment was obtained at a dose of 200 mg/day. (www.actabiomedica.it)

Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy

Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR. To test clinical efficacy of adjunctive therapy with fenofibrate in pharmacoresistant ADNFLE\NFLE patients, we first demonstrated the effectiveness of fenofibrate in a mutated mouse model displaying both disease genotype and phenotype. We first tested the efficacy of fenofibrate in transgenic mice carrying the mutation in the α4-nAChR subunit (Chrna4S252F) homologous to that found in humans. Subsequently, an add-on protocol was implemented in a clinical setting and fenofibrate was administered to pharmacoresistant NFLE patients. Here, we show that a chronic fenofibrate diet markedly reduced the frequency of large inhibitory postsynaptic currents (IPSCs) recorded from cortical pyramidal neurons in Chrna4S252F mice, and prevented nicotine-induced increase of IPSC frequency. Moreover, fenofibrate abolished differences between genotypes in the frequency of sleep-related movements observed under basal conditions. Patients affected by NFLE, nonresponders to traditional therapy, by means of adjunctive therapy with fenofibrate displayed a reduction of seizure frequency. Furthermore, digital video-polysomnographic recordings acquired in NFLE subjects after 6months of adjunctive fenofibrate substantiated the significant effects on control of motor-behavioral seizures. Our preclinical and clinical studies suggest PPARα as a novel disease-modifying target for antiepileptic drugs due to its ability to regulate dysfunctional nAChRs.

Improved Sleep Quality in Patients Affected by Nocturnal Frontal Lobe Epilepsy (NFLE) Treated with Lacosamide: A Two Cases Report

Nocturnal Frontal Lobe Epilepsy (NFLE) is a form of focal epilepsy with heterogeneous clinical presentation of morpheic seizures that tend to cluster overnight, with a good response to carbamazepine (CBZ). We report two cases of NFLE patients associated with sleep disorders, successfully treated with lacosamide 200 mg/day. We hypothesized that lacosamide, in relation to its multiple action mechanisms, can have positive effects not only on seizures control but also on sleep disorders associated with them.

Analysis of the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal epilepsy.

To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy (NFLE). Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects. Genomic DNA was extracted, and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing. No CHRNA7 gene mutation was detected in all of the NFLE patients. However, five single nucleotide polymorphisms (SNPs) in sporadic cases were found, located in exons 5, 6, and 7 of the CHRNA7 gene. Among them, c.690G>A and c.698A>G are known SNPs, while c.370G>A, c.654C>T, and c.497-498delTG were newly discovered SNPs. These SNPs were also found in some of the healthy controls. No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE. The CHRNA7 gene is probably not responsible for NFLE in this population.

A novel mutation of the nicotinic acetylcholine receptor gene CHRNA4 in a Chinese patient with non-familial nocturnal frontal lobe epilepsy

So far, only two mutations in the CHRNA4 gene (in three studies) and one mutation in the CHRNB2 gene had been identified in the patients with sporadic nocturnal frontal lobe epilepsy (NFLE). The absence of mutations in the candidate genes in the majority of sporadic NFLE patients suggest that they are rare loci for the disease, but the necessity of performing genetic testing for sporadic cases should not be neglected. We designed mutation screening of exon 5 of CHRNA4, exon 5 of CHRNB2, and exon 6 of CHRNA2 in a group of 56 Chinese sporadic NFLE cases. A de novo missense mutation in the transmembrane domain M2 segment of the α4 subunit of the neuronal nicotinic acetylcholine receptor, c.823A>T, was found in a 15 year-old right-handed male, but was not observed in his parents and 400 control chromosomes. The mutation decreased the surrounding hydrophobicity and slightly altered secondary structure of the protein. No mutations were found in CHRNB2 and CHRNA2.

Effects of antiepileptic treatment on sleep and seizures in nocturnal frontal lobe epilepsy

To study the effects of antiepileptic treatment on sleep parameters and video-polysomnography (VPSG) seizures in nocturnal frontal lobe epilepsy (NFLE). Twenty patients with a clinical and VPSG diagnosis of NFLE (baseline polysomnography [PSG]) underwent a clinical follow-up and performed a second VPSG after effective antiepileptic treatment lasting for at least 6 months. Conventional sleep measures, cyclic alternating pattern (CAP) parameters, and objective VPSG seizures were assessed in NFLE patients before and after treatment and were compared with the results of 20 age- and gender-matched control subjects. Antiepileptic treatment determined a partial reduction of objective VPSG seizures of approximately 25% compared to baseline condition. Alterations of most conventional sleep measures recovered normal values, but nonrapid eye movement (NREM) sleep instability remained pathologically enhanced (CAP rate, +26% compared to controls) and was associated with persistence of daytime sleepiness. Residual epileptic events and high levels of unstable NREM sleep can define a sort of objective resistance of both seizures and disturbed arousal system to the therapeutic purpose of the antiepileptic drugs in NFLE. This finding could determine the need for new therapeutic options in this particular form of epilepsy.

Nocturnal Frontal Lobe Epilepsy and the Acetylcholine Receptor

Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy characterized by a wide spectrum of stereotyped motor manifestations, mostly occurring during non rapid eye movements sleep. NFLE is underdiagnosed since semiological similarities make it difficult to distinguish NFLE from parasomnias. In 1994, authors reported families with NFLE inherited as an autosomal dominant trait and they introduced the term of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). A family history of possible NFLE is found in about 25% of cases. The genetic bases of the disease have been detected in a minority of cases. Mutations causing a gain of function of the neuronal nicotinic acetylcholine receptors were reported in 3 different subunits. This review discusses the clinical aspects of NFLE and the diagnostic procedures. Furthermore, the genetic aspects are outlined. The main differentiating features characterizing NFLE are: (a) several attacks per night at any time during the night; (b) brief duration of the attacks; (c) stereotyped motor pattern. Nocturnal video-polysomnography is crucial for the diagnosis. Neurological examination in NFLE/ADNFLE is normal. About 30% of NFLE cases are resistant to antiepileptic drugs. Concerning the genetics, putative susceptibility nucleotide variations affecting the promoter of the CRH gene and altering the corticotrophin-releasing hormone levels have been reported in some NFLE patients. Distinguishing NFLE seizures from paroxysmal nonepileptic sleep disorders is often difficult and sometimes impossible on clinical grounds alone. Nocturnal video-polysomnography is mandatory. Further genetic studies could help the diagnosis and treatment in NFLE patients.

Distinctive polysomnographic traits in nocturnal frontal lobe epilepsy

To describe the polysomnographic features and distribution of epileptic motor events, in relation to conventional sleep measures and cyclic alternating pattern (CAP) parameters, in 40 untreated patients with nocturnal frontal lobe epilepsy (NFLE). We analyzed the basal polysomnographic recordings of 40 patients (20 male and 20 female; mean age: 31 ± 10 years) with a diagnosis of nocturnal frontal lobe epilepsy. Conventional sleep measures and CAP parameters were assessed. Polysomnographic recordings were subdivided in sleep cycles. The distribution of the epileptic motor events (including minor motor events, paroxysmal arousals, tonic-dystonic, or hyperkinetic seizures and epileptic nocturnal wandering) was analyzed throughout: total sleep time, non-rapid eye movement (NREM) and REM sleep, light sleep (S1 + S2), slow wave sleep (SWS), each sleep cycle, CAP or non-CAP sleep, phase A and phase B of CAP. Only clear epileptic motor events supported by video-polysomnographic evidence were taken into consideration. Polysomnographic findings of patients with NFLE were compared with those of 24 age- and gender-balanced healthy subjects without sleep complaints. Compared to controls, patients with NFLE showed a significant increase in wake after sleep onset, SWS duration, and REM latency, whereas REM sleep duration was significantly lower in NFLE patients. The patients with NFLE showed a significant increase of CAP time, CAP rate (72% vs. 32% in control group), CAP cycles, and mean duration of a CAP sequence. These findings were associated with a significant enhancement of all subtypes of the A phases of CAP (mainly subtype A1). A total of 139 epileptic motor events supported by video-polysomnographic evidence were counted: 98% of all seizures occurred in NREM sleep and 72% of NREM seizures emerged from SWS, the latter being particularly collected in the first sleep cycles and decreasing in frequency together with the progressive decline of deep sleep. Ninety percent of total NREM seizures occurred during a CAP sequence, and CAP-related seizures occurred in association with a phase A. Significant polysomnographic alterations seem to emerge in patients with NFLE (increased REM latency, epileptic fragmentation of SWS, and increase of CAP rate). The analysis of seizure distribution showed that most epileptic events occurred in SWS, with predominance in the first sleep cycle and decreasing in frequency together with the homeostatic decline of SWS across the night. Within the NREM sleep, CAP is a manifestation of unstable sleep and represents a powerful predisposing condition for the occurrence of nocturnal motor seizures, which arise in concomitance with a phase A.

Features of the K-complex waves in refractory nocturnal frontal lobe epilepsy

To investigate the features of the K-complex (Kc) in refractory nocturnal frontal lobe epilepsy (NFLE) and its relationship with spike discharges (Sds) and clinical seizures. Long-term video-electroencephalographic (VEEG) monitoring was used to collect Kc data from NFLE patients and age- and sex-matched controls. We compared the morphological and frequency changes in Kcs between the intractable NFLE group and the control group. Also, the morphological changes in Kcs with Sds and seizures were compared with the other Kcs in NFLE patients. In the NFLE group, frequency, amplitude, and rising slope (except duration) were higher than in the control group. Out of the 30 seizures recorded, nine (30%) commenced after a Kc. These Kcs had higher amplitudes than the other Kcs in the NFLE group; there was no difference in duration or rising slope. Additionally, 28 (13.86%) of 202 Kcs of the NFLE group occurred in conjunction with Sds; there were no obvious morphological differences compared with other Kcs. Kc activity increases in NFLE, especially prior to a clinical seizure. This reflects an unstable sleep condition, which suggests a correlation between Kc and epileptic activities including seizures and Sds.

Can Homemade Video Recording Become More Than a Screening Tool?

Can Homemade Video Recording Become More Than a Screening Tool?

Rats Harboring S284LChrna4Mutation Show Attenuation of Synaptic and Extrasynaptic GABAergic Transmission and Exhibit the Nocturnal Frontal Lobe Epilepsy Phenotype

Mutations of genes encoding alpha4, beta2, or alpha2 subunits (CHRNA4, CHRNB2, or CHRNA2, respectively) of nAChR [neuronal nicotinic ACh (acetylcholine) receptor] cause nocturnal frontal lobe epilepsy (NFLE) in human. NFLE-related seizures are seen exclusively during sleep and are characterized by three distinct seizure phenotypes: "paroxysmal arousals," "paroxysmal dystonia," and "episodic wandering." We generated transgenic rat strains that harbor a missense mutation S284L, which had been identified in CHRNA4 in NFLE. The transgenic rats were free of biological abnormalities, such as dysmorphology in the CNS, and behavioral abnormalities. The mRNA level of the transgene (mutant Chrna4) was similar to the wild type, and no distorted expression was detected in the brain. However, the transgenic rats showed epileptic seizure phenotypes during slow-wave sleep (SWS) similar to those in NFLE exhibiting three characteristic seizure phenotypes and thus fulfilled the diagnostic criteria of human NFLE. The therapeutic response of these rats to conventional antiepileptic drugs also resembled that of NFLE patients with the S284L mutation. The rats exhibited two major abnormalities in neurotransmission: (1) attenuation of synaptic and extrasynaptic GABAergic transmission and (2) abnormal glutamate release during SWS. The currently available genetically engineered animal models of epilepsy are limited to mice; thus, our transgenic rats offer another dimension to the epilepsy research field.

The FLEP scale in diagnosing nocturnal frontal lobe epilepsy, NREM and REM parasomnias: Data from a tertiary sleep and epilepsy unit

To test the usefulness of the FLEP scale in diagnosing nocturnal frontal lobe epilepsy (NFLE), arousal parasomnias, and REM sleep behavior disorder (RBD). The FLEP scale was applied to 71 subjects (60 male; 11 female; aged 54 +/- 21) referred to an outpatient's sleep and epilepsy unit for diagnostic assessment of nocturnal motor-behavioral episodes, which turned to be arousal parasomnias (11 subjects), NFLE (14 subjects), or idiopathic RBD (46 subjects), based on the findings of in-lab full night video polysomnography with extended EEG montages. The sensitivity of the scale as a diagnostic test for NFLE was 71.4%, the specificity 100%, the positive predictive value 100%, and the negative predictive value 91.1%. The FLEP scale gave an incorrect diagnosis in 4/71 (5.6%) of the cases, namely NFLE patients with episodes of nocturnal wandering, and uncertain diagnostic indications in 22/71 subjects (30.9%). The FLEP scale shows high positive and negative predictive values in diagnosing NFLE versus arousal parasomnias and RBD. However, the scale is associated with a real risk of misdiagnosis in some patients and gives uncertain indications in about one-third of cases, mainly RBD. Our investigation highlights the inadequacy of some of the items in the scale. The item investigating wandering, as presently formulated, may be unable to distinguish nocturnal wandering from sleepwalking. The items about "recall" and "clustering" of the events throughout the night may increase the likelihood of mistaking RBD for seizures. Further testing of the reliability of the FLEP scale items appears to be needed.

Nocturnal epileptic seizures versus the arousal parasomnias

We review here the clinical features of Nocturnal Frontal Lobe Epilepsy (NFLE) and the arousal parasomnias, to define possible differential diagnostic criteria and their inter-observer reliability, and to determine whether both conditions share a common disturbance of arousal mechanisms. Polysomnographic recordings defined several types of seizures in NFLE: Paroxysmal Arousals (PA), Nocturnal Paroxysmal Dystonia (NPD), Epileptic Nocturnal Wanderings (ENW). There are however several difficulties with the diagnosis of NFLE, not the least being that EEG discharges during the seizures are not universally found. These diagnostic difficulties are highlighted, as well as the fact that studies of the inter-observer reliability of the video polysomnographic features of NFLE were found unsatisfactory, especially for the PA. When NFLE patients and their relatives were matched to control subjects and analysed in regard to personal and family history for the parasomnias, the arousal parasomnias were reported significantly higher by patients with NFLE and their relatives. This higher recurrence of a personal and family history for the parasomnias in NFLE patients suggests that the two conditions share a common underlying mechanism. Based on evidence from Autosomal Dominant NFLE, a genetic disorder with mutations in nicotinic acetylcholine receptors(nAchR), we hypothesise that arousal parasomnias and NFLE both, have abnormal arousal mechanisms in the dorsal cholinergic arousal branch triggering peculiar motor patterns in the medial frontal lobe regions.

CHRNA2 mutations are rare in the NFLE population: Evaluation of a large cohort of Italian patients

Objective Forty-six nocturnal frontal lobe epilepsy (NFLE) patients (in which the involvement of the CHRNA4 and CHRNB2 genes coding for neuronal nicotinic acetylcholine receptor (nAChRs) subunits associated to the disease were previously excluded) were analyzed for the presence of mutations in the CHRNA2 gene coding for the alpha2 subunit of the same receptor, which has been recently associated with the disease. Methods Mutational screening was performed by sequencing two polymerase chain reaction-amplified CHRNA2 DNA fragments, spanning the whole exon 6 and exon 7, respectively, which code for ∼75% of the mature protein and contain all four transmembrane domains contributing to the ion pore. Results No mutations were identified in the analyzed region of CHRNA2. Conclusions These data demonstrate the rarity of the identified CHRNA2 mutations in NFLE patients, supporting the recently reported hypothesis of a restricted role for this gene in the disease.

To Sleep, Perchance to Seize: Surgery Ameliorates Nocturnal Frontal Lobe Seizures

Surgical Treatment of Drug-resistant Nocturnal Frontal Lobe Epilepsy. Nobili L, Francione S, Mai R, Cardinale F, Castana L, Tassi L, Sartori I, Didato G, Citterio A, Colombo N, Galli C, Lo Russo G, Cossu M. Brain 2007;130 (Pt 2):561–573. Of the cases with nocturnal frontal lobe epilepsy (NFLE) 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.

Nocturnal Frontal Lobe Epilepsy: There is Bad, Good, and Very Good News!

Surgical Treatment of Drug-Resistant Nocturnal Frontal Lobe Epilepsy. Nobili L, Francione S, Mai R, Cardinale F, Castana L, Tassi L, Sartori I, Didato G, Citterio A, Colombo N, Galli C, Lo Russo G, Cossu M. Brain 2007;130(Pt 2):561–573. Of the cases with nocturnal frontal lobe epilepsy (NFLE) 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.

Sleep‐related Minor Motor Events in Nocturnal Frontal Lobe Epilepsy

Nocturnal frontal lobe epilepsy (NFLE) is characterized by a wide spectrum of sleep-related motor manifestations of increasing complexity, ranging from major episodes to brief motor events (minor motor events, MMEs). NFLE patients may exhibit a large quantity of MMEs in the form of short-lasting stereotyped movements. Whereas major episodes are considered epileptiform manifestations, it remains unclear whether the MMEs are related to epileptiform discharges (EDs). To study the relation between EDs and the occurrence of MMEs, we report a detailed neurophysiolgical evaluation in NFLE subjects explored by using implanted electrodes. The median value of ED-related movements was 71.8%. Motor expression in relation to epileptiform discharge was surprisingly variable; no peculiar expression of MMEs could be attributed to the presence of EDs. Our data suggest that ED-associated MMEs are extremely polymorphous, and no univocal relation to EDs can be identified. We hypothesize that MMEs are not a direct effect of epileptiform discharge (i.e., not epileptic in origin), but the result of aspecific disinhibition of innate motor patterns. We warn clinicians that the epileptic nature of minimal motor phenomena in NFLE cannot be established on the clinical phenomenology of the event.

Excessive Daytime Sleepiness and Subjective Sleep Quality in Patients with Nocturnal Frontal Lobe Epilepsy: A Case‐Control Study

Nocturnal frontal lobe epilepsy (NFLE) may be associated with sleep fragmentation and reduced sleep efficiency. Daytime sleepiness and disturbed sleep quality have been reported in some patients. We investigated the occurrence of daytime sleepiness-related symptoms and subjective sleep quality in patients with NFLE in comparison with matched controls. Patients with NFLE at a single epilepsy center and matched controls randomly selected from the general population self-administered questionnaires on daytime sleepiness-related symptoms and subjective sleep quality [Epworth sleepiness scale (ESS), Bologna questionnaire on sleepiness-related symptoms (BQS), Berlin questionnaire]. Thirty-three patients with NFLE and 27 controls were enrolled. "Tiredness after awakening" and "spontaneous mid-sleep awakenings" were more frequent in NFLE patients than in controls (36.4% versus 11.1%, p = 0.04, and 50.0% versus 22.2%, p = 0.03). The frequency of excessive daytime sleepiness (EDS) did not differ between groups. Posthoc analysis showed that patients with a complaint of "midsleep awakenings" had higher ESS and BQS scores than those without (7.3 versus 4.3, p = 0.004, and 5.0 versus 2.2, p = 0.001, respectively) and more frequent "tiredness after awakening" (56.3% versus 18.8%, p = 0.03). Patients with NFLE have no pathological level of EDS with respect to controls. However, daytime sleepiness-related symptoms could be more frequent in a subgroup of patients with subjective disturbed sleep quality, irrespective of the perceived frequency of seizures.