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PubMed2007

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1998

Frontal lobe functions and dysfunctions.

Frontal lobe syndromes with personality change are well known for about 150 years but mysteries of their underlying anatomophysiological mechanisms have started to unfold in recent years. The frontal lobe accommodates an extension of the primary motor (precentral) cortex, the premotor region and the interhemispherically located supplementary motor region, both of them forming area 6 and its subdivisions. The anterior and inferior frontal structures (and also the eye field, area 8) belong to the prefrontal region. The prefrontal cortex is also involved in motor action: in its initiation, planning, designing and sequencing rather than its mere execution. This requires drive and initiative to move, their deficits resulting in moderate to extreme apathy. Forces of motivation are likely to be mediated via the fronto-orbital cortex (known as an extension of the temporo-limbic system) which also exerts inhibitory influences on prefrontal functioning, and disinhibitory frontal lobe syndromes (from tactlessness to aggression) are the result of frontobasal impairment. A special form of frontal-motor cortex disconnection may occur in childhood: in the rare Rett syndrome and, with limitation to the prefrontal cortex, in the common Attention Deficit Hyperactivity Disorder (ADHD). The initiation of movement is based upon the constant influx of afferent-sensory messages from posterior cerebral regions and strong mesiodorsal thalamic connections, providing information for each following initiatory prefrontal motor impulse which depends on such information from the past moment. This "Working Memory" appears to be the keystone of mental and motor prefrontal function. Becoming unnecessary in the next moments, the afferent signals undergo immediate extinction due to inhibitory fronto-orbital impulses. It is assumed that the classical absence attack with generalized spike-waves of frontal onset causes a "suspension of the working memory" and thus permits immediate postictal recuperation of frontal functions. The gap between afferent and efferent signals in the working memory is likely to permit neurocognitive-processes and, in Homo sapiens, a widened gap is thought to provide a basis for reflection and cogitation uniquely human properties.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Asymmetrical involvement of frontal lobes in social reasoning.

The frontal lobes are widely implicated in logical reasoning. Recent neuroimaging studies suggest that frontal lobe involvement in reasoning is asymmetric (L>R) and increases with the presence of familiar, meaningful content in the reasoning situation. However, neuroimaging data can only provide sufficiency criteria. To determine the necessity of prefrontal involvement in logical reasoning, we tested 19 patients with focal frontal lobe lesions and 19 age- and education-matched normal controls on the Wason Card Selection Task, while manipulating social knowledge. Patients and controls performed equivalently on the arbitrary rule condition. Normal controls showed the expected improvement in the social knowledge conditions, but frontal lobe patients failed to show this facilitation in performance. Furthermore, left hemisphere patients were more affected than right hemisphere patients, suggesting that frontal lobe involvement in reasoning is asymmetric (L>R) and necessary for reasoning about social situations.

Adult↗
PubMed2000

The Frontal Lobe Score: part I: construction of a mental status of frontal systems.

OBJECTIVE: To develop a bedside mental status examination to assess the behavioural effects of damage to the frontal lobes. DESIGN: A prospective clinical comparison of patients with cerebral lesions of different locations. SUBJECTS: A total of 118 subjects were examined: 27 patients with cerebral lesions confined to the frontal lobes, 25 patients with cerebral lesions without involvement of the frontal lobes, 18 patients with mixed frontal/nonfrontal lesions, and 48 normal control subjects. MEASURES: Twenty-three mental status tests, clinical examinations and rating scales that had been reported as indicative of frontal lobe function were brought together. By statistical analysis, 12 tests and a neurobehavioural rating scale were selected. These constitute the Frontal Lobe Score (FLS). RESULTS: The FLS detected pure frontal lesions with a sensitivity of 77.7%. It discriminated patients with frontal lesions from normal control subjects with a specificity of 100%. Differentiation from patients with nonfrontal lesions was obtained with a specificity of 84%. CONCLUSION: The Frontal Lobe Score is a useful screening instrument for the clinical detection of effects of frontal lobe damage.

Adult↗
PubMed1996

Stereological MRI volumetry of the frontal lobe.

Stereology was used to measure frontal lobe volume on magnetic resonance imaging (MRI) scans in a multi-observer repeated-measures trial in 17 adults. Prior to measurement, MR image volumes were reoriented into coronal sections perpendicular to the bicommissural plane. Three observers blinded to subject identify repeatedly used fixed grid stereology to estimate frontal lobe volumes, defined as all sections of the frontal lobe anterior to the anterior commissure. The lateral ventricles were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was 0.03. The inter-rater correlation coefficient = 0.95 for three raters; intra-rater correlation coefficients = 0.95-0.98. A comparison was made between stereological and traditional edge tracing measurement of the frontal lobe volumes. The overall correlation between the two methods was 0.95. The use of internal landmarks to define orientation and 3-D orthogonal views to define frontal lobe boundaries on 3-D images was critical to obtaining repeatable measurements. Frontal lobe volumetry by brain MR used to estimate small differences postulated to occur in certain psychiatric and neurologic disorders requires high precision and repeatability. Stereology, a semi-automated method, can reliably estimate frontal lobe volumes. This method may distinguish small frontal lobe volume differences within individuals and between groups.

Aged↗
PubMed2005

Attentional inhibition in patients with focal frontal lobe lesions.

Patients with unilateral, frontal lobe damage and matched controls performed an identity negative priming task as a measure of inhibition in selective attention. Control participants demonstrated a normal negative priming effect, as evidenced by slower reaction times when a previously to-be-ignored item became the target on a subsequent trial (distractor suppression). On the other hand, patients with left medial frontal lobe damage showed positive priming in the distractor suppression condition suggesting facilitation of distractor information. Patients with right frontal lobe damage showed an unreliable pattern of negative priming, some demonstrating an absence of negative priming and others demonstrating enhanced negative priming in the distractor suppression condition. Neither patient group nor controls demonstrated slower responses on a target-to-distractor condition included to evaluate a noninhibitory (i.e., episodic retrieval) account of negative priming. Taken together, our results suggest that (a) the negative priming effect represents active inhibition of a distractor representation, rather than a noninhibitory mismatch between retrieval episodes, and (b) that the frontal lobes, especially the left frontal lobes, contribute to this active inhibition.

Adult↗
PubMed1998

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↗
PubMed1999

The differentiation of semantic dementia and frontal lobe dementia (temporal and frontal variants of frontotemporal dementia) from early Alzheimer's disease: a comparative neuropsychological study.

The authors compared age-matched groups of patients with the frontal and temporal lobe variants of frontotemporal dementia (FTD; dementia of frontal type [DFT] and semantic dementia), early Alzheimer's disease (AD), and normal controls (n = 9 per group) on a comprehensive neuropsychological battery. A distinct profile emerged for each group: Those with AD showed a severe deficit in episodic memory with more subtle, but significant, impairments in semantic memory and visuospatial skills; patients with semantic dementia showed the previously documented picture of isolated, but profound, semantic memory breakdown with anomia and surface dyslexia but were indistinguishable from the AD group on a test of story recall; and the DFT group were the least impaired and showed mild deficits in episodic memory and verbal fluency but normal semantic memory. The frontal and temporal presentations of FTD are clearly separable from each other and from early AD.

Age Factors↗
PubMed1996

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↗
PubMed2007

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↗
PubMed2001

Effect of divalproex-lamotrigine combination therapy in frontal lobe seizures.

CONTEXT: Patients with intractable frontal lobe seizures represent a difficult subclass of patients with epilepsy. When medications fail, surgical outcomes typically have not been as successful as medial temporal lobe resections. The combination therapy of valproic acid (divalproex sodium) and lamotrigine has shown promising results in patients with uncontrolled seizures. OBJECTIVE: To determine outcome in patients with intractable frontal lobe seizures who were treated with the combination of divalproex and lamotrigine. DESIGN: A nonrandomized, open-label, add-on trial. SETTING: Outpatients evaluated and treated at a tertiary care referral facility. PATIENTS: Twenty-one patients between 16 and 65 years old were studied. Patients were required to have failed at least 3 prior trials with antiepilepsy drugs. Criteria for frontal lobe onset included 1 or more of the following: frontal lesion on scan, positive ictal single-photon emission computed tomographic scan, symptoms consistent with frontal lobe onset, or an electroencephalogram (surface or invasive) consistent with frontal lobe onset. INTERVENTION: Patients were treated with divalproex-lamotrigine combination therapy for 1 year. MAIN OUTCOME MEASURES: The main outcome measured was seizure reduction. Safety and tolerability were also evaluated. RESULTS: Four patients discontinued therapy. Ten of the remaining 17 became completely free of seizures. Two rashes occurred, but did not lead to discontinuation of therapy. The most common adverse events were tremor and weight gain. CONCLUSION: Divalproex-lamotrigine combination therapy is a reasonable alternative in intractable frontal lobe epilepsy.

Adolescent↗
PubMed2001

Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury.

BACKGROUND: Investigations have suggested that frontal lobe abnormalities are a prominent feature of the alcoholic brain, indicated by impaired neuropsychological performance on tests of frontal lobe function and by reduced frontal lobe volume in neuroimaging and neuropathological examinations. White matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature of this change has not been well-characterized. METHOD: To investigate the susceptibility of frontal lobe white matter to alcohol-associated metabolic change and to understand the nature of alcohol-related white matter injury, 1H magnetic resonance spectroscopy (MRS) was used to measure concentrations of metabolites in frontal white matter (FWM) and parietal white matter (PWM) of recently detoxified alcoholics (RDA) and nonalcoholic controls (CON). Concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean length of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years). RESULTS: Analysis of variance (ANOVA) revealed a group by region of interest interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were similar in RDA and CON. In addition, RDA had an 11.8% increase (averaged across both regions of interest) in brain white matter Ins relative to CON. Reductions in FWM NAA were associated with a longer drinking history in the RDA group, but this result was not found when both age and drinking history were used to predict the level of FWM NAA. CONCLUSIONS: Alcohol-associated reductions in FWM NAA may be the result of neuronal loss or dysfunction in the metabolism of NAA. While alcohol-induced oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in excitatory amino acid pathways, and axonal damage or destruction secondary to glutamate-mediated excitotoxicity during alcohol withdrawal may cause frontal lobe-specific reductions in NAA. Elevations in brain white matter Ins may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage.

Adult↗
PubMed2003

Electrophysiology of the frontal lobe.

The electrophysiology of the frontal lobe appears to be unimpressive when the view is limited to the routine EEG recording of a healthy waking adult. There is usually low voltage fast activity, which becomes more pronounced when recorded with depth leads. Three special EEG patterns of marginal to slightly abnormal character are discussed: a) rhythmical midfrontal 6-7/sec activity of juveniles, b) rhythmical midfrontal sharp 4-6/sec activity of infancy and early childhood with arousal from sleep, and c) frontal intermittent rhythmical delta activity (FIRDA) in waking adults with frontopolar maximum, possibly related to thought processes under abnormal conditions. With extension of the frequency range, ultraslow (DC-like) as well as fast beta (gamma, 40-80/sec) and ultrafast activity (80-1000/sec) are found particularly over the frontal lobes. Ultraslow baseline shifts are arousal-related and mixed with overlying ultrafast waves. Attention control and the "working memory" involve chiefly the dorsolateral prefrontal cortex, investigated with P300 responses and likely to show ultrafast spectra. Perception-related 40-80/sec gamma activity has been thought to be associated with the entrance into consciousness. Initiation and design of motor activity spreads from prefrontal to the frontomotor cortex, associated with powerful event-related potentials: contingent negative variation (CNV) and "Bereitschafts potential" ("readiness potential," RP). Neuroscientific research of the highest frontal lobe functions has become a very active domain of neuroimaging. With the use of the extended frequency range, EEG and also evoked potential studies could add further information with acquisition in real time. Ultrafast frequency ranges presented in computerized frequency analysis and mapping might show impressive correlates of highest frontal lobe functions.

Arousal↗