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Frontal lobe epilepsy.

Frontal lobe epilepsy accounts for only 10-20% of the patients in surgical series, but the incidence in non-surgical patient cohorts seems to be much higher. The typical clinical presentation of the seizures includes contralateral clonic movements, uni- or bilateral tonic motor activity as well as complex automatism. The yield of surface EEG may be limited due to the difficulty in detection of mesial or basal foci, and the patient may be misdiagnosed as having non-epileptic events. In addition, in patients with mesial frontal foci the epileptiform discharges may be mislateralized ("paradoxical lateralization"). Therefore, epilepsy surgery has been commonly considered as less promising in patients with frontal lobe epilepsy. However, the advent of sophisticated neuroimaging techniques, particularly MRI with epilepsy-specific sequences, has made it possible to delineate the epileptogenic lesion and detect a specific etiology, in an increasing number of patients. Thus, the success rate of epilepsy surgery in frontal lobe epilepsy is currently comparable to temporal lobe epilepsy, if the candidates are carefully selected. Patients with frontal lobe epilepsy who do not respond to anticonvulsive medication, and who are not eligible for epilepsy surgery may benefit from alternative approaches such as electrical brain stimulation.

Anticonvulsants↗

Deficits in executive functions and motor coordination in children with frontal lobe epilepsy.

Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8-16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7-16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8-12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.

Adolescent↗

A study of the relationship between the seizure focus and 1H-MRS in temporal lobe epilepsy and frontal lobe epilepsy.

Several studies of temporal lobe epilepsy (TLE) patients have investigated the relationship between the seizure focus and 1H magnetic resonance spectroscopy (1H-MRS). There have also been a few reports in other types of partial epilepsy. We examined the relationship between the seizure focus and the reduction in N-acetylaspartate: creatine (NAA : Cr) ratio using 1H-MRS in both TLE and frontal lobe epilepsy (FLE) patients. We studied 21 patients with unilateral TLE and seven patients with unilateral FLE. We used a 1.5 Tesla magnetic resonance unit (Signa Horizon; General Electric). Approximately 15 x 15 x 20 mm3 voxel of interest (VOI) was placed over the anterior portion of the bilateral hippocampus in the TLE patients, and the anterodorsal position of bilateral frontal lobe in the FLE patients. The seizure focus was identified by interictal scalp electro-encephalogram (EEG). In the TLE patients the NAA : Cr ratios were reduced in the seizure focus, while in the FLE patients they were not always reduced in the seizure focus. In the TLE patients the coincidence rate between the seizure focus and the reduction in the NAA:Cr ratio was 90% (19 of 21 patients), while in the FLE patients the coincidence rate was only 57% (four of seven patients).

Adult↗

Nocturnal frontal lobe epilepsy.

Nocturnal frontal lobe epilepsy (NFLE) is a condition primarily characterized by seizures occurring exclusively or predominantly during sleep, the semiology of which suggest a frontal lobe origin and, more specifically, the involvement of the orbitofrontal or mesial frontal regions. It is usually considered as a relatively benign and homogeneous epileptic syndrome, the neuropsychological impact of which should be minimal. However, several issues complicate this view. 1. NFLE is rather a heterogeneous disorder which includes both sporadic and familial forms, various seizure types, and drug resistance in about 30% of patients. 2. The frontal origin of seizures has rarely been demonstrated, and mainly relies on the presence of ictal signs suggestive of frontal lobe epilepsy, but which might only reflect the propagation of ictal discharges of extrafrontal origin. 3. NFLE-like seizures were recently found to be associated with temporobasal cortical dysplasia, or an insular epileptogenic zone, including one patient with autosomal dominant frontal lobe epilepsy (ADNFLE). 4. No study has yet specifically evaluated the neuropsychological profile of patients with NFLE. Available data suggest that behavioral problems and mental retardation might be associated with ADNFLE, especially when it is related to a mutation of the nicotinic receptor subunits. Conversely, the majority of NFLE patients does not seem to present with gross cognitive disturbance, even though many of these patients complain of chronically disrupted sleep and daytime sleepiness. Further research is warranted in this field, keeping in mind that the neural networks underlying NFLE remain poorly known and might primarily involve extrafrontal brain regions in some patients.

Cerebral Cortex↗

Surgical outcome and prognostic factors of frontal lobe epilepsy surgery.

Frontal lobe epilepsy (FLE) surgery is the second most common surgery performed to treat pharmacoresistant epilepsy. Yet, little is known about long-term seizure outcome following frontal lobectomy. The aim of this study is to investigate the trends in longitudinal outcome and identify potential prognostic indicators in a cohort of FLE patients investigated using modern diagnostic techniques. We reviewed 70 patients who underwent a frontal lobectomy between 1995 and 2003 (mean follow-up 4.1 +/- 3 years). Data were analysed using survival analysis and multivariate regression with Cox proportional hazard models. A favourable outcome was defined as complete seizure-freedom, allowing for auras and seizures restricted to the first post-operative week. The estimated probability of complete seizure-freedom was 55.7% [95% confidence interval (CI) = 50-62] at 1 post-operative year, 45.1% (95% CI = 39-51) at 3 years, and 30.1% (95% CI = 21-39) at 5 years. Eighty per cent of seizure recurrences occurred within the first 6 post-operative months. Late remissions and relapses occurred, but were rare. After multivariate analysis, the following variables retained their significance as independent predictors of seizure recurrence: MRI-negative malformation of cortical development as disease aetiology [risk ratio (RR) = 2.22, 95% CI = 1.40-3.47], any extrafrontal MRI abnormality (RR = 1.75, 95% CI = 1.12-2.69), generalized/non-localized ictal EEG patterns (RR = 1.83, 95% CI = 1.15-2.87), occurrence of acute post-operative seizures (RR = 2.17, 95% CI = 1.50-3.14) and incomplete surgical resection (RR = 2.56, 95% CI = 1.66-4.05) (log likelihood-ratio test P-value < 0.0001). More than half of patients in favourable prognostic categories were seizure-free at 3 years, and up to 40% were seizure-free at 5 years, compared to <15% in those with unfavourable outcome predictors. These data underscore the importance of appropriate selection of potential surgical candidates.

Adolescent↗

Topiramate in frontal lobe epilepsy.

BACKGROUND: Frontal lobe epilepsy (FLE) is a type of epilepsy that is difficult to treat and there are few studies about the use of topiramate (TPM). AIM OF THE STUDY: To evaluate the efficacy and tolerability of TPM monotherapy in FLE. METHODS: The study group consisted of 55 (33 male; 22 female) patients. TPM was administered as a first drug (n = 16) or converted after previous treatment (n = 39). All patients were followed every 3 months for at least 1 year. The patients were subdivided into two groups: 'newly diagnosed' patients and 'difficult-to-treat' patients. RESULTS: Overall, all patients completed the 1-year study. At the end of follow-up, 10 patients showed disappearance of seizures and 33 patients showed improvement in seizure frequency. In particular, among the newly diagnosed patients 6/16 patients showed complete cessation of seizures and 5/16 patients showed very good response; in the other group, 4/39 patients showed complete cessation and 4/39 patients showed a very good response. No patients of both groups had worsening of seizures. No treatment-limiting adverse events associated with TPM were reported. CONCLUSIONS: TPM is effective in newly diagnosed patients with FLE; TPM can be considered for the treatment of FLE.

Adolescent↗

The wide clinical spectrum of nocturnal frontal lobe epilepsy.

Nocturnal frontal lobe epilepsy (NFLE) has become clinically relevant in recent years. NFLE represents a spectrum of clinical manifestations, ranging from brief, stereotyped, sudden arousals, often recurring several times per night, sometimes with a quasi-periodic pattern, to more complex dystonic-dyskinetic seizures and to prolonged "somnambulic" behaviour. Episodes of increasing intensity have been labelled as paroxysmal arousal (PA), nocturnal paroxysmal dystonia (NPD) and episodic nocturnal wandering (ENW). NFLE affects both sexes with a higher prevalence for men, is frequently cryptogenetic and displays a strong familial trait for parasomnias and epilepsy (NFLE). Seizures appear more frequently between 14 and 20 years of age, but can affect any age and tend to increase in frequency during life. Interictal and ictal scalp electroencephalography (EEG) are often normal, the use of sphenoidal leads may be helpful. Carbamazepine taken at night is often effective at low doses, but a third of the patients are resistant to anti-epileptic drugs (AED) treatment. A familial form, characterized by an autosomal dominant transmission, has also been described. Autosomal dominant nocturnal frontal lobe epilepsy is a genetic variant of NFLE, in itself both clinically and biologically heterogeneous. NFLE should be suspected in the presence of frequent stereotyped paroxysmal nocturnal motor events arising or persisting into adulthood. Videopolysomnography is mandatory to confirm the diagnosis.

Journal Article↗

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs. resections plus multiple subpial transections; MST), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short-term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the 3 month follow-up examination, patients with temporal lobectomy had improved frontal functions, whereas patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure-free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MSTs of the precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favourable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short-term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated with frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adult↗

[Frontal lobe epilepsy in infancy: is there a benign partial frontal lobe epilepsy?].

INTRODUCTION: Only the organic and cryptogenic forms of frontal lobe epilepsy have been admitted by the ILAE, but according to several reports in the literature, it probably exists also an idiopathic form, at present not well recognized. OBJECTIVE: To study the differences between the organic and the cryptogenic forms of frontal epilepsy in our patients, that might indicate the presence of idiopathic cases within the presumed cryptogenic group. MATERIAL AND METHODS: All patients diagnosed of frontal lobe epilepsy, EEG registered, at the neuropediatric clinic of our hospital during 1993-1996, were selected: 30 patients under 14 years of age that were classified as organic (10 cases) or cryptogenic (20 cases) according to CT or MRI findings. The Mann-Whitney test and the Fisher exact test were performed for statistical analysis. Five patients with peculiar neurocognitive symptoms, epilepsy-related, are described in detail. RESULTS: Significative differences between the organic and cryptogenic forms of frontal lobe epilepsy were not found except for the tendency of cryptogenic EEG foci to spread beyond the frontal lobe, to generalize and to be associated with foci of other localizations. Epileptic status, either convulsive or not convulsive, were a frequent complication in both groups. CONCLUSIONS: The identification of an idiopathic form of frontal lobe epilepsy is difficult by its low prevalence as compared to the cryptogenic and organic forms, by the tendency of frontal seizures to become epileptic status, which predicts an intractable epilepsy, and by the clinical characteristics essential to frontal discharges: heterogeneity, frequent impairment of consciousness and specially the neurocognitive semiology, including dementia, that occurs as a critic or paracritic phenomenon, and that sometimes may develop or be accentuated by antiepileptic medication.

Anticonvulsants↗

Frontal lobe epilepsy in childhood.

Frontal lobe epilepsy is poorly understood and often unrecognized by health care workers caring for children. We sought to better characterize frontal lobe epilepsy in childhood and help delineate this condition from other nonepileptic events. We reviewed pediatric patients admitted to the Comprehensive Epilepsy Program at the University of Alberta Hospitals with a proven diagnosis of frontal lobe epilepsy. Twenty-two patients, 13 males and 9 females, were studied. Age of onset was variable from 10 months to 16 years (mean 7.5 years). Seizures were brief (30 seconds to 2 minutes), stereotypic, nocturnal (17/21), and frequent (3-22/night). Clinical features included explosive onset, screaming, agitation, stiffening, kicking or bicycling of the legs, and incontinence. The diagnosis of frontal lobe epilepsy was not made in any child before referral. The referring diagnosis was sleep disturbance (10), psychiatric problems (6), or other seizure types (6). Interictal electroencephalogram was usually normal (18/21). Long-term video electroencephalographic monitoring demonstrated frontal (9) or bifrontal (13) epileptic discharges. Magnetic resonance imaging was normal in most patients (18/21). Seizure control was difficult, with only half (11/21) the patients being controlled on medication. Three intractable patients went on to epilepsy surgery and became seizure-free. Frontal lobe epilepsy in childhood is a distinct epilepsy syndrome with characteristic features. The seizures are brief, stereotypic, nocturnal, and frequent. Electroencephalogram and magnetic resonance imaging are usually normal. The condition is often misdiagnosed as a sleep disorder or psychiatric problem. Seizures are difficult to control but may respond to carbamazepine, valproic acid, or epilepsy surgery.

Adolescent↗

Thalamic asymmetry on interictal SPECT in patients with frontal lobe epilepsy.

BACKGROUND: Interictal brain single photon emission computed tomography (SPECT) is useful for the detection of seizure focus. Recent reports indicate a hypoperfusion in the ipsilateral thalamus as a seizure focus on interictal SPECT in temporal lobe epilepsy. In frontal lobe epilepsy (FLE), however, the alteration of perfusion in the thalamus has not been well documented. This study aimed to assess whether perfusion analysis on the thalamus may add useful information for the detection of epileptic foci in patients with FLE. METHODS: Interictal brain SPECT was performed in 11 patients with FLE. The asymmetry index for the thalamus and frontal area in the SPECT image was calculated in order to compare the laterality of the seizure foci. RESULTS: Thalamic asymmetry was seen in seven patients (64%), while cortial asymmetry was seen in six patients (55%). The concordance with the lateralization of the seizure foci was 6/7 (86%) in the thalamus, and 4/6 (67%) in the frontal area. Four patients showed only thalamic asymmetry. Concordance with the lateralization of the seizure focus was found in all of them. CONCLUSION: These preliminary results suggest that hypoperfusion in the thalamus may have a complementary role to lateralize the epileptic foci in patients with FLE.

Adolescent↗

Neuropsychological consequences of epilepsy surgery in frontal lobe epilepsy.

The present study investigated the effect of frontal lobe surgery on "cognitive functions", which have previously been shown to be discriminative in the evaluation of non-resected patients with frontal lobe epilepsy (FLE). The cognitive outcome was evaluated with particular consideration of the side (left/right), the site (lateral, orbital, mesial, premotor/SMA), the type of surgery (resections vs resections plus Multiple Subpial Transections), and seizure outcome. The evaluation is based on 33 patients with left (n = 17) or right (n = 16) frontal surgery. Forty-five patients who underwent successful left (n = 21) or right (n = 24) temporal lobectomy served as controls. The neuropsychological examination covered speed/attention, motor sequencing/coordination, response maintenance/inhibition, short-term memory, and language. With the exception of short term memory, the chosen tests were discriminative in determining preoperative frontal lobe dysfunctions but they did not differentiate patients with a different lateralization or localization of the frontal focus. At the three month follow-up examination, patients with temporal lobectomy had improved frontal functions, while patients with frontal lobe surgery showed a mild deterioration. Within the frontally resected group, completely seizure free patients had significantly improved short-term memory. Further consideration of the side, site and the type of the frontal resection indicated that patients with premotor/SMA surgery and patients with precentral/central MST had additional impairment after surgery. Premotor/SMA resections led to a deterioration in response maintenance/inhibition and if performed left sided also to deteriorated language functions. The latter impairment could be clearly related to transient aphasia directly after surgery. Irrespective of pareses observed immediately after surgery, patients with MST's of precentral/central areas displayed additional problems in motor coordination at the follow-up examination. In this group the seizure outcome was also less favorable. In summing up, frontal lobe surgery does not cause any considerable additional impairment in the short term follow-up. However, caution is recommended when surgery or MST affect functional relevant cortex (here the prefrontal/SMA and precentral/central area). Finally, a release of functions associated to frontal areas not affected by surgery is suggested, when seizures are successfully controlled by surgery.

Adolescent↗

Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy.

Patients with frontal lobe epilepsy (FLE), patients with temporal lobe epilepsy (TLE), and matched controls were administered a test of response inhibition and set shifting (switching) (Color Word Interference Test, CWIT). Patients with FLE were impaired relative to the controls across all conditions of the CWIT, with the FLE patients showing disproportionate impairment in the Inhibition and Inhibition/Switching conditions. In contrast, the TLE patients did not differ from controls. Further analysis of the patient groups revealed that patients with left FLE were impaired relative to those with right FLE, left TLE, and right TLE in the Inhibition condition. In the Inhibition/Switching condition, patients with left FLE and left TLE were impaired relative to their right-sided counterparts. Finally, performance by the TLE group in the Inhibition/Switching condition was correlated with seizure frequency. These data suggest that patients with FLE, but not TLE, show impaired inhibition and set shifting relative to controls. In addition, side of the seizure focus and seizure frequency may contribute to executive dysfunction in patients with epilepsy.

Adult↗

A de novo mutation in sporadic nocturnal frontal lobe epilepsy.

Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy has not been associated with genetic defects. A 30-year-old woman diagnosed as having sporadic nocturnal frontal lobe epilepsy was found to have a de novo Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within the second transmembrane domain of CHRNA4 in association with autosomal dominant nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in families with different ethnic backgrounds.

Adult↗

EEG findings in frontal lobe epilepsies.

As a group, epilepsies of frontal lobe origin are thought to be poorly localized using surface EEG recordings. This finding may depend on the specific areas of frontal lobe from which the seizures originate or the pathologic substrate. We reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who underwent epilepsy surgery. The specific area of the frontal lobe where seizures originated was determined by 1) intracranial ictal EEG recordings, or 2) the presence of a structural lesion, identified by imaging studies in patients who achieved complete seizure control following surgery. We differentiated patients whose seizures began in the dorsolateral frontal convexity from those whose seizures began in the medial frontal region, and we correlated EEG findings in the interictal, postictal, and ictal states with seizure semiology, pathologic substrate, and surgical outcome. Four of nine patients had seizures originating in the dorsolateral frontal convexity and five had medial frontal onset seizures. Patients whose seizures originated from the dorsolateral convexity had focal interictal epileptiform abnormalities that localized to the region of seizure onset. Patients whose seizures began in the medial frontal region had either no interictal epileptiform abnormality or had multifocal epileptiform discharges. Patients whose seizures began in the dorsolateral convexity showed focal electrographic seizure activity that was localizing. This rhythmic fast activity did not appear to be substrate-specific. Patients whose seizure onset localized to the medial frontal region did not show focal electrographic seizure at clinical onset. We conclude that the scalp EEG recordings of frontal lobe epilepsies contain features that enable differentiation of seizures originating from two different regions of the frontal lobe.

Adolescent↗

Frontal lobe epilepsy: the next frontier.

Frontal lobe epilepsy, the great new epileptological challenge, presents enormous difficulties that still preclude a more profound understanding at the present time. The major subdivision of the frontal lobe into a prefrontal and premotor portion is the first step toward a better and yet limited comprehension of the frontal lobe epilepsies. Prefrontal implies higher mental functions (e.g., ictal forced thinking); rapid generalization to full grand mal evolves quite often from prefrontal foci. The frontal accentuation of classical generalized 3/sec spike-wave absences adds to the conceptual difficulties of the frontal lobe epilepsies. The unique type of disturbed consciousness in classical absences is presumed to be based upon ictal "suspension of the working memory." Limbic components (via orbitofrontal and cingulate mechanisms) also play an important role. Correlations between ictal semiologies and regional frontal lobe functions are still quite controversial.

Electroencephalography↗

Autosomal dominant nocturnal frontal lobe epilepsy: demonstration of focal frontal onset and intrafamilial variation.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a newly recognized autosomal dominant partial epilepsy. We studied seizure localization and intrafamilial variation using video-EEG monitoring (VEM) and functional neuroimaging in two pairs of subjects from unrelated families. The clinical features of seizures were similar from seizure to seizure in each individual, but varied between individuals. As is often found in frontal lobe epilepsies, ictal EEG localization was imprecise in three of four cases. One patient showed a consistent left fronto-polar onset that was corroborated by congruent focal hypometabolism on interictal PET and focal hyperperfusion on ictal single photon emission computed tomography (SPECT). A second case studied with ictal SPECT showed a right parasagittal, midfrontal focus. We conclude that this autosomal dominant epilepsy syndrome, which in one of the two families was due to a known neuronal nicotinic acetylcholine receptor mutation, causes frontal lobe foci that are unilateral and in variable locations in different individuals.

Adolescent↗

General neuropsychological characteristics of frontal lobe epilepsy.

The neuropsychological characteristics of frontal lobe epilepsy have rarely been reported, with neuropsychological indicators usually being related to subjects with other forms of neurological damage. In this study we assessed the performance of 74 subjects with frontal lobe epilepsy (42 with left, 32 with right frontal epileptic foci) on a series of measures thought to be sensitive to frontal lobe dysfunction and compared to 57 subjects with temporal lobe epilepsy (31 with left, 26 with right epileptic foci). The results indicated a number of measures that could be considered sensitive to frontal lobe epileptic dysfunction. However, the pattern of results did not indicate consistent deficits to be associated with frontal lobe epileptic dysfunction. There are a number of unique factors associated with epilepsy that need to be considered, and these may account for the variable pattern of results obtained. In particular, the rapid propagation of frontal lobe seizures both bilaterally and to other cortical regions has to be considered.

Adolescent↗