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PubMed2001

Neuronal nicotinic acetylcholine receptors and autosomal dominant nocturnal frontal lobe epilepsy: a critical review.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a distinct human epileptic syndrome. In some families, it is associated with mutations of the alpha4 or the beta2 subunit of the neuronal nicotinic acetylcholine receptor (nAChR). It has been suggested that these mutations are the causative factors responsible for the induction and expression of this syndrome. However, the pathogenic mechanisms leading to ADNFLE are unknown and, in this review, we discuss the following yet unresolved questions concerning the involvement of mutated nAChRs in the phenotypic development of the disorder: (1) why do seizures associated with ADNFLE arise explicitly from the frontal lobe of the neocortex? (2) why do the seizures arise mainly from sleep? (3) why does ADNFLE starts predominantly during childhood? A survey of our current knowledge on neocortical and thalamic cholinergic systems, including their ontogenetic development, leads us to the conclusion that there are, at least at the moment, no convincing answers to these questions. Furthermore, we believe that, even in those cases where mutations of the alpha4 or the beta2 subunit of the nAChR cosegregate with ADNFLE, there must be some crucial additional factors contributing to the development of the specific symptoms of ADNFLE.

Animals↗
PubMed1995

Unilateral spatial neglect due to a haemorrhagic contusion in the right frontal lobe.

We report two cases of unilateral spatial neglect associated with an isolated right frontal lobe lesion. Case 1 was a 59-year-old, right-handed man, who developed a left hemiplegia, disorientation, and frontal lobe neglect associated with a haemorrhagic contusion following a head injury. Case 2 was a 55-year-old, right-handed man, who also developed disorientation and frontal lobe neglect secondary to a haemorrhagic contusion following a head injury. 99mTc HM-PAO SPECT revealed an isolated reduction in the regional cerebral blood flow (CBF) around the haematoma in the frontal lobe; blood flow to remaining parts of the brain was normal. Damage to the right frontal lobes of these patients was confirmed as being the cause of the unilateral spatial neglect in accordance with the results of CBF studies.

Attention↗
PubMed1995

Impaired use of organizational strategies in free recall following frontal lobe damage.

Free recall, use of organizational strategies, and interference effects were assessed in patients with frontal lobe lesions and control subjects. In three experiments, patients with frontal lobe lesions exhibited impaired free recall and reduced use of organizational strategies in tests of memory. Reduced use of strategies was observed on tests of recall of unrelated items, as measured by subjective organization, and on tests of recall of related items, as measured by both category clustering and subjective organization. Frontal patients benefited from strategy instruction at either study or test, suggesting that both encoding and retrieval processes are impaired by frontal lobe damage. These findings indicate that the free recall impairments exhibited by patients with frontal lobe lesions may be caused at least in part by deficits in the use of organizational strategies. In addition, when first-list learning was matched for patients and control subjects, patients with frontal lobe lesions exhibited relatively increased sensitivity to proactive interference during second-list learning.

Aged↗
PubMed2005

Assessment of anosognosia in persons with frontal lobe damage: clinical utility of the Mayo-Portland Adaptability Inventory (MPAI).

OBJECTIVES: To determine if the Mayo-Portland Adaptability Inventory (MPAI) demonstrates clinical utility in differentiating between persons with severe TBI and frontal lobe damage/anosognosia and persons with mild TBI and no frontal lobe damage. PARTICIPANTS: Forty-three persons with TBI and documented frontal lobe damage (mean age = 34; mean time since injury = 5.2 years) and 69 persons with mild TBI and no frontal lobe damage (mean age = 34.3; mean time since injury = 4.8 4.8 years). MEASURE: MPAI. RESULTS: Total inventory and select sub-category difference scores were significantly greater in the frontal lobe group than in the non-frontal lobe group. However, as expected, there was no significant difference between the two groups on the mobility sub-category difference scores. CONCLUSIONS: The MPAI appears to be potentially clinically useful in assessing for frontal lobe damage and associated anosognosia in patients with TBI.

Adult↗
PubMed2001

Frontal lobe seizure propagation: scalp and subdural EEG studies.

PURPOSE: To study propagation properties of focally originating frontal lobe seizures: principally direction and promptness of ictal spread. METHOD: Forty-eight scalp EEG-recorded and 17 subdurally recorded seizures in two separate groups of patients were visually scrutinized. RESULTS: Initial propagation was directed more commonly to contiguous frontal cortex than to the opposite hemisphere in both studies: 58% and 86% for scalp and subdural recordings, respectively. Eighteen (38%) of scalp EEG seizures propagated within 5-10 s of apparent onset, whereas 16 (33%) did so after 11-20 s; no evidence of propagation could be discerned in the remaining 14 (29%). Of subdurally recorded attacks, only four (24%) propagated in the first 4 s; six (35%) did so after a delay of 5-10 s; six (35%) either failed to propagate or did so after > or =20-s latency. Latency to initial propagation was between 5 and 20 s in 41 (63%) of the 65 seizures in both studies. Ictal activity remained within the frontal lobe of origin for > or =10 s in 39 (81%) of scalp-recorded seizures and 11 (65%) of subdural seizures. It remained so confined for > or =15 s in 26 (54%) and nine (53%), respectively. Twenty-four (50%) of scalp-recorded seizures displayed evidence of opposite hemisphere (bisynchronous or other contralateral) involvement, occurring 5-10 s after onset in eight (17%) seizures and 10-20 s after onset in 16 (33%). Similarly, the subdural study documented spread to the opposite hemisphere in 11 (65%) of seizures with a latency ranging from 1 to 45 s. CONCLUSIONS: Frontal lobe seizures in this study propagated less promptly than reputed, and initial spread occurred more commonly to the frontal lobe of origin than to the opposite hemisphere. Such properties underlie the good lateralizing value of clinical semiology of frontal lobe seizures.

Brain Mapping↗
PubMed1999

[Autosomal dominant nocturnal frontal lobe epilepsy: the syndrome].

The identification of the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in 1994 was rapidly followed by that of other familial forms of non lesional partial epilepsies (familial temporal lobe epilepsy, autosomal dominant partial epilepsy with variable foci). Since then around forty families with ADNFLE have been described, most of them having only 3 or 4 affected individuals. The epilepsy usually begins during childhood (mean age at onset: 11 years). The seizures mainly consist of motor elements which can be dystonic, tonic or hyperkinetic (bipedal automatisms, pelvic thrashing movements...), often preceded by a non specific aura. They are brief and frequent, taking place at night, in clusters. Some patients also present some diurnal seizures. One third of the patients report the occurrence of rare secondarily generalized tonic-clonic seizures. There is a large intra-familial variability as to age of onset, intensity of the manifestations and the course of the epilepsy. During the period of highest frequency of seizures, some patients may present moderate neuropsychological disturbances concordant with frontal dysfunctioning, or transitory behavioral disorders. The seizures often subside with age and may even disappear at adulthood. The most effective antiepileptic drug is carbamazepine, however pharmacoresistance is seen in 20 to 30 p. 100 of the cases. Interictal EEG shows non specific epileptiform anomalies with a frontal predominance, often seen solely on sleep recording, in more than half of all patients. Ictal EEG does not always give evidence of definite ictal discharges. The clinical heterogeneity of ADNFLE as it is especially observed in very variable types of auras which are non localizing, aside form the EEG's own limits, makes it difficult to localize the primary epileptic focus with certainty in the frontal lobe in all cases. In all, the clinical and electrical spectrum of ADNFLE is large, and the topographical identification of these familial frontal lobe epilepsies sets the same problems as for sporadic, classical cryptogenic frontal lobe epilepsies.

Age of Onset↗
PubMed1990

Frontal-lobe cognitive dysfunction in conduct disorder adolescents.

Behavioral similarities between antisocial behavior disorders and frontal-lobe cerebral impairment have led to suggestions that conduct disorders are attributable to disinhibition deficit associated with frontal-lobe cerebral functions. This study compared the performance of 21 conduct disorder adolescents on measures of cognitive processes associated with frontal-lobe functions with that of a matched comparison sample. Conduct disorder adolescents performed more poorly on measures sensitive to frontal-lobe dysfunction (conceptual perseveration, poorly sustained attention, impaired sequencing on memory and motor tasks), but not on non-frontal-lobe specific cognitive measures. Although the findings support a neurobehavioral explanation of antisocial behavior as a product of cerebral disinhibition, caution is urged in overinterpreting causal relationships through neurobehavioral data.

Adolescent↗
PubMed2005

[Proteomic comparison between human cerebellums and frontal lobes].

OBJECTIVE: To compare the results of proteomics between the cerebellum and frontal lobe of the aged. METHOD: Proteins were isolated from human cerebellums and frontal lobes and separated by two-dimensional (2D) gel electrophoresis. The proteins were then stained with silver or colloidal coomassie blue to produce a high-resolution map of the proteome. Selected proteins from this map were in-gel digested with trypsin and the resulting tryptic peptides were analyzed by MALDI-TOF mass spectrometry and MALDI TOF/TOF tandem mass spectrometry. The mass spectrometric data were used to identify the proteins through searches of the SWISSPROT protein sequence database. RESULTS: Three up-regulated protein spots in 2D gels of cerebellums were found as compared with those of frontal lobes. These protein spots were identified as antioxidant protein 2, creatine kinase precursor, fructose-bisphosphate aldolase C. Two down-regulated proteins in cerebellums were identified as pyruvate kinase M1 isozyme and glial fibrillary acidic protein. 30 common proteins, the expressions of which were not altered between cerebellums and frontal lobes, were also identified. CONCLUSIONS: These data will be used for future studies of differential protein expression in neurological disorders. Some proteins are useful for discovering the molecular mechanisms of degenerative dementia and brain aging.

Aged↗
PubMed1994

Phosphorus magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy.

Phosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 +/- 0.05 vs 7.00 +/- 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 +/- 6.0 vs 23.0 +/- 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.

Adolescent↗
PubMed2005

Postictal mania associated with frontal lobe epilepsy.

A 38-year-old man, possibly with frontal lobe epilepsy, developed postictal mania. The changes in psychiatric symptoms and laboratory examinations over time were investigated in two episodes of postictal mania, using long-term electroencephalography with closed circuit television (EEG/CCTV) monitoring, magnetoencephalography (MEG), and single-photon emission computed tomography (SPECT) to elucidate the underlying mechanism of postictal mania. According to the clinical symptoms, the postictal manic episodes of this case had four phases: a lucid interval, manic phase, hypomanic phase, and recovery phase. EEG showed forced normalization during the florid manic phase. The serial findings of EEG, MEG, and SPECT during the postictal manic episodes suggest that functional changes in bilateral frontal lobes, especially the right frontal lobe, right temporal lobe, and right paralimbic area, are crucial in the development of postictal mania, and that these functional changes are dynamic.

Adult↗
PubMed1999

Multiple system atrophy with remarkable frontal lobe atrophy.

The autopsy findings of a multiple system atrophy (MSA) patient with remarkable frontal lobe atrophy are described. The patient was a 65-year-old woman with a 13-year history of untreatable parkinsonism, dysautonomia and progressive motor aphasia. The brain weight was 810 g, and there was remarkable atrophy of the cerebrum predominantly in the frontal lobe, striatum, pons and cerebellum. Microscopic examination revealed a preserved cortical structure with laminar gliosis in the sixth layer of the precentral and superior frontal gyri of the frontal lobe, and postcentral gyrus and inferior parietal lobule of the parietal lobe. The second layer of the cortices of these regions were also revealed to be in a spongy state, and mild cell loss was seen in the fifth and six layers. The frontal lobe white matter showed a mild loss of myelinated fibers and axons, and mild gliosis. Glial cytoplasmic inclusions (GCIs) were abundantly observed in the deep layer of the cortex in the regions mentioned above, and were more abundant in the white matter of the frontal and parietal lobes, callosal body, and internal, external and extreme capsules. There was severe degeneration in the olivopontocerebellar and striatonigral systems, and GCIs in widespread regions of the brain. No Pick bodies, Lewy bodies, ballooned neurons, senile plaques, or significant amounts of neurofibrillary tangles were detected. There were no vascular changes. Thus, this was a verified MSA patient with progressive aphasia and remarkable frontal lobe atrophy. We indicate a possible involvement of the cerebral lobes in MSA.

Aged↗
PubMed2002

Surgery to treat focal frontal lobe epilepsy in adults.

OBJECTIVE: To report clinical, neuropathological, and outcome data for a series of adult patients with focal frontal lobe epilepsy (fFLE) who underwent nonlobar resection restricted to the frontal lobe. METHODS: Sixty-eight adult cases (24 female and 44 male patients) were included in the study, on the basis of prospectively collected data that were retrospectively evaluated. There were 68 lesionectomies, 17 of which were combined with multiple subpial transection, with a mean follow-up period of 28.4 +/- 23.3 months. Cases involving additional extrafrontal surgery were excluded. RESULTS: Thirty-seven patients underwent invasive preoperative evaluations, and 31 underwent noninvasive evaluations. Intraoperative electrocorticography was used in 32% of cases. There were 24 tumors, 18 dysgenetic lesions, 14 gliotic lesions, and 10 vascular malformations. Fifteen tumors were of glial origin, one was a dysembryoplastic neuroepithelial tumor, and eight were gangliogliomas. The most common dysgenetic lesions were hamartomas (15 cases). Outcomes (classified into four Engel groups) were as follows: Class I, 54%; Class II, 19%; Class III, 15%; Class IV, 12%. Seizure-free rates were comparable for tumor and dysgenesis cases and were not as good for vascular malformation and gliosis cases. Outcome differences were not significant with respect to aura presence, side of surgery, age at the time of surgery, and age at seizure onset. There were 3 cases of surgical complications, 10 cases of transient neurological disturbances, and 1 case involving a permanent neurological deficit. No deaths occurred. CONCLUSION: Outcomes with fFLE surgery have improved, compared with historical series. fFLE resections restricted to the frontal lobe did not yield seizure-free rates as good as those for comparable nonfocal frontal lobe epilepsy series. All fFLE cases demonstrated histological lesions. fFLE surgery was associated with a higher risk of transient neurological deficits, most likely because of the necessity for multiple subpial transection. The outcomes and higher rates of invasive evaluations and intraoperative electrocorticography indicate the special complexities of frontal lobe epilepsy. The permanent neurological disability rate was low in this series, and there were no deaths.

Adolescent↗
PubMed1994

Specificity of changes in cerebral blood flow in patients with frontal lobe dementia.

Eight patients with a clinical diagnosis of probable Alzheimer's disease, eight patients with the clinical diagnosis of frontal lobe dementia, and eight controls were examined with single photon emission tomography (SPECT) using 99Tc-HMPAO. Patients with Alzheimer's disease and those with frontal lobe dementia met DSM-III-R criteria for mild dementia and were in the early stages of the illness. Compared with patients with Alzheimer's disease, the group with frontal lobe dementia had significantly lower blood flow in the frontal lobes (dorsolateral and orbital), the anterior temporal cortex, and the basal ganglia. Within the frontal lobe dementia group, blood flow was significantly lower in the orbital than in the dorsal frontal cortex, and in the anterior temporal than in the dorsal temporal cortex. The present study shows the specificity of changes in regional cerebral blood flow in the diagnosis of different types of dementia, and supports the importance of orbitofrontal, anterior temporal, and basal ganglia dysfunction in the production of the psychiatric syndrome of frontal lobe dementia.

Aged↗
PubMed1995

Proton magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy.

Proton magnetic resonance spectroscopic imaging (1H MRSI) has demonstrated decreased N-acetyl compounds (NA) in the epileptogenic hippocampus in patients with temporal lobe epilepsy. We studied 8 patients with frontal lobe epilepsy and found mean NA/creatine (Cr) in the epileptogenic frontal lobe decreased by 27% compared with that of the contralateral homologous region (1.81 +/- 0.36 vs 2.49 +/- 0.60, p < 0.008). In every patient, NA/Cr was decreased in the epileptogenic region by at least 5%. These findings suggest that 1H MRSI may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.

Aspartic Acid↗
PubMed2002

Performance on tests of frontal lobe function reflect general intellectual ability.

Recent studies have indicated that performance on tests of frontal lobe function are highly associated with general intellectual ability (g). Some authors have even claimed that the available evidence does not support a more specific account of frontal lobe function than to provide a general intellectual function for the performance of goal directed tasks. We examined the relationship between performance on the WAIS-R (as a measure of g) and performance on standard tests of frontal lobe function in 123 healthy individuals. Our results demonstrate that in healthy individuals (i) performance on the most popular tests of frontal lobe function shares significant variance, and (ii) a large proportion of that shared variance is highly associated with performance on the Wechsler Adult Intelligence Scales-Revised (WAIS-R), so that the tests are similar to the extent that they measure g. Performance on the Modified Card Sorting Test (MCST), however, is not related to g. The results support the claim that many tests of frontal lobe function measure primarily a non-specific intellectual function but also indicate that some tests, like the MCST, may be assessing more specific cognitive operations.

Adolescent↗