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S F Berkovic

Publications and source records attributed to S F Berkovic.

At least 55 records · Page 3Linked to original sources
PubMed2001

Genetics of the epilepsies.

Recent molecular insights into the human idiopathic epilepsies have suggested the central role of ligand-gated and voltage-gated ion channels in their etiology. So far, genes coding for sodium and potassium channel subunits as well as a nicotinic cholinergic receptor subunit have been identified for mendelian idiopathic epilepsies. In vitro and in vivo studies of mutations demonstrate functional changes, allowing new insights into mechanisms underlying hyperexcitability. Similarly, spontaneous murine epilepsy models have been associated with calcium channel molecular defects. The major challenge before us in understanding the genetics of the epilepsies is to identify genes for common forms of epilepsy following complex inheritance. Once such genes are discovered, the gene-gene-environmental interactions producing specific epilepsy syndromes can be explored.

Animals↗
PubMed2001

Transcallosal resection of hypothalamic hamartomas, with control of seizures, in children with gelastic epilepsy.

OBJECTIVE: Hypothalamic hamartomas (HHs) are associated with precocious puberty and gelastic epilepsy; the seizures are often refractory to antiepileptic medications and associated with delayed development and disturbed behavior. The current opinion is that surgery to treat intrahypothalamic lesions is formidable and that complete excision is not technically achievable. We report our experience with a transcallosal approach to the resection of HHs. METHODS: Five children (age, 4-13 yr) with intractable epilepsy and HHs underwent preoperative clinical, electroencephalographic, and imaging evaluations. Two patients experienced only gelastic seizures, and three patients experienced mixed seizure disorders with drop attacks; all experienced multiple daily seizures. Patients were evaluated with respect to seizures, cognition, behavior, and endocrine status 9 to 37 months (mean, 24 mo) after surgery. The HHs were approached via a transcallosal-interforniceal route to the third ventricle and were resected using a microsurgical technique and frameless stereotaxy. RESULTS: Complete or nearly complete (>95%) excision of the HHs was achieved for all patients, with no adverse neurological, psychological, or visual sequelae. Two patients experienced mild transient diabetes insipidus after surgery. Two patients developed appetite stimulation, but no other significant endocrinological sequelae were observed. Three patients are seizure-free and two patients have experienced only occasional, brief, mild gelastic seizures after surgery, all with reduced antiepileptic medications. On the basis of parental reports and our own subjective observations, the children also exhibited marked improvements in behavior, school performance, and quality of life. CONCLUSION: Complete or nearly complete resection of HHs can be safely achieved via a transcallosal approach, with the possibility of seizure freedom and neurobehavioral improvements.

Child Behavior↗
PubMed2000

CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the beta2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes and characterized by an approximately 10-fold increase in acetylcholine sensitivity. CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE.

Acetylcholine↗
PubMed2000

Men may be more vulnerable to seizure-associated brain damage.

BACKGROUND: Repetitive seizures may be associated with progressive neuronal damage measurable by quantitative MRI. OBJECTIVE: To investigate whether gender is a risk factor for this damage. METHODS: Sixty patients with refractory temporal lobe epilepsy (TLE) (28 men, 32 women) and 54 healthy controls (28 men, 26 women) were compared by quantitative MRI methods. RESULTS: Male patients had ipsilateral hemicranial volume loss of 12% (CI 8% to 16%) and contralateral volume loss of 7% (CI:3% to 11%) compared with male controls (p < or =0.004, analysis of variance). Female patients were 4% (CI:0.3% to 8%, p = 0.04) smaller than controls in the ipsilateral hemicranium, and not different contralaterally. The patient-to-control difference was greater in men than in women for the ipsilateral (p = 0.003) and contralateral hemicranial volume (p = 0.02). In men, 14% of the ipsilateral (F = 4.7, p = 0.004) and 16% of the contralateral (F = 5.1, p = 0.03) hemicranial volume loss could be attributed to generalized tonic clonic seizures. Compared with controls, patients averaged a 29% smaller ipsilateral and a 5% smaller contralateral hippocampus. CONCLUSION: Men with TLE have more brain atrophy than women with TLE. Seizure frequency is a factor contributing to reduced brain volumes in men but not in women. Men, therefore, may be more vulnerable to seizure-associated brain abnormalities.

Adult↗
PubMed2000

Idiopathic generalized epilepsy: lack of significant microdysgenesis.

BACKGROUND: The idiopathic generalized epilepsies (IGE) are classically regarded as due to a functional abnormality. However, microscopic microdysgenetic changes have been reported in the majority of cases by one group. OBJECTIVE: To independently evaluate the microscopic microdysgenetic changes in a controlled, blinded study. METHODS: Five brains with IGE and five age-matched control brains were collected. Blocks were taken from nine standardized Brodmann areas, both hippocampi, and cerebellum. Slides were examined independently by two neuropathologists blinded to patient group, who qualitatively scored microdysgenetic features on standardized data sheets. The results were compared and any discrepancies were rescored by the pathologists together using a double-header microscope. Quantitative neuronal profile counts in the molecular layer in standardized Brodmann areas of frontal cortex and in deep frontal white matter were performed. RESULTS: Microdysgenetic features in nine Brodmann areas, hippocampi, and cerebellum were not increased in brains from subjects with IGE compared with control brains. Quantitative neuronal profile counts in the molecular layer of frontal cortex and deep frontal white matter were not increased in IGE compared with controls. CONCLUSIONS: This controlled, blinded study did not replicate the results of previous reports of microdysgenesis in IGE. Although factors such as syndrome heterogeneity and sample size may explain the discrepancy, technical factors could also play a role. The current ion channel hypothesis for the pathogenesis of IGE does not preclude microscopic or ultramicroscopic abnormalities and the search for these should continue.

Adult↗
PubMed2000

TLE patients with postictal psychosis: mesial dysplasia and anterior hippocampal preservation.

The authors studied six patients with refractory temporal lobe epilepsy and postictal psychosis using quantitative MRI and histopathology, and compared the results with 45 patients with temporal lobe epilepsy without postictal psychosis. Total hippocampal volumes were not different between the two groups. However, patients with postictal psychosis had a relatively preserved anterior hippocampus, and temporal lobe dysplasia was more frequent (p = 0.006, chi-square test). These findings may be associated with the clinical symptoms.

Adult↗
PubMed2000

Phenotypic characterization of an alpha 4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse.

Neuronal nicotinic acetylcholine receptors (nAChR) are present in high abundance in the nervous system (Decker et al., 1995). There are a large number of subunits expressed in the brain that combine to form multimeric functional receptors. We have generated an alpha(4) nAChR subunit knock-out line and focus on defining the behavioral role of this receptor subunit. Homozygous mutant mice (Mt) are normal in size, fertility, and home-cage behavior. Spontaneous unconditioned motor behavior revealed an ethogram characterized by significant increases in several topographies of exploratory behavior in Mt relative to wild-type mice (Wt) over the course of habituation to a novel environment. Furthermore, the behavior of Mt in the elevated plus-maze assay was consistent with increased basal levels of anxiety. In response to nicotine, Wt exhibited early reductions in a number of behavioral topographies, under both unhabituated and habituated conditions; conversely, heightened levels of behavioral topographies in Mt were reduced by nicotine in the late phase of the unhabituated condition. Ligand autoradiography confirmed the lack of high-affinity binding to radiolabeled nicotine, cytisine, and epibatidine in the thalamus, cortex, and caudate putamen, although binding to a number of discrete nuclei remained. The study confirms the pivotal role played by the alpha(4) nAChR subunit in the modulation of a number of constituents of the normal mouse ethogram and in anxiety as assessed using the plus-maze. Furthermore, the response of Mt to nicotine administration suggests that persistent nicotine binding sites in the habenulo-interpeduncular system are sufficient to modulate motor activity in actively exploring mice.

Aggression↗
PubMed2000

APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy.

The authors analyzed the association between APOE epsilon4 genotype and clinical and MRI findings in 43 refractory temporal lobe epilepsy patients. The distribution of the alleles were normal. Ten patients (23%) had an APOE epsilon 4 allele and had an earlier onset of habitual seizures (with epsilon4 5 +/- 5 years; without epsilon4 15 +/- 10 years). Quantitative MRI findings were not influenced by the APOE epsilon4 genotype. APOE epsilon4 may shorten the latency between an initial injury and seizure onset.

Adult↗
PubMed2000

Video analysis of acute motor and convulsive manifestations in sport-related concussion.

OBJECTIVES: To describe the motor and convulsive manifestations in acute sports-related head injury. METHODS: A total of 234 cases of concussive injuries during the 1995 through 1997 football seasons were obtained from the Australian Football League Medical Officers Association injury survey. Of these, 102 cases were recorded adequately on television videotape and were analyzed by two independent observers using a standardized recording form detailing injury mechanics and clinical features of the episodes. Motor and convulsive features were correlated with mechanical variables and with duration of loss of consciousness using linear modeling techniques. RESULTS: Tonic posturing occurred in 25 subjects, clonic movements in 6, righting movement in 40, and gait unsteadiness in 42. In one subject the tonic and clonic features were sufficiently prolonged to be deemed a concussive convulsion. The only risk factor for tonic posturing using logistic regression was the presence of loss of consciousness (p = 0.0001). There was a trend toward facial impact being an independent predictor of tonic posturing but this did not reach significance. No other independent variable predicted the development of clonic movements, righting movements, or gait unsteadiness. CONCLUSIONS: Subtle motor manifestations such as tonic posturing and clonic movements commonly occur in concussion; the main predictive factor for tonic posturing is the presence of loss of consciousness. The authors speculate that these clinical features are due to brainstem dysfunction secondary to biomechanical forces inducing a transient functional decerebration.

Brain Concussion↗
PubMed2000

Deaths due to brain injury among footballers in Victoria, 1968-1999.

OBJECTIVES: To determine the frequency and nature of fatal brain injuries occurring in Australian football. SETTING: State of Victoria, January to July 1999. DESIGN: Retrospective case series of football-related deaths identified from the coronial autopsy records of the Victorian Institute of Forensic Medicine (1990-1999) and newspaper reports (1968-1989). MAIN OUTCOME MEASURES: Coronial autopsy findings and circumstances of injury. RESULTS: 25 deaths associated with Australian football were identified, nine due to brain injury. Coronial findings in the brain-injury deaths were intracranial haemorrhage in eight patients and infarct in the territory of the middle cerebral artery in one. In three of four cases of subarachnoid haemorrhage, vertebral artery trauma was noted. In all but one case, injury occurred as an accidental part of play. CONCLUSIONS: The most common findings in deaths due to brain injury in Australian football were intracranial haemorrhage, including subarachnoid haemorrhage from vertebral artery injury.

Adolescent↗
PubMed2000

"Pressure to laugh": an unusual epileptic symptom associated with small hypothalamic hamartomas.

Gelastic seizures are the hallmark of the epilepsy syndrome associated with hypothalamic hamartomas. Patients typically develop cognitive deterioration and refractory seizures. The authors describe three patients with small hypothalamic hamartomas without these features and thus identify a mild end to the clinical spectrum. All had the unusual symptom of "pressure to laugh," often without actual laughter. This symptom could be dismissed as psychogenic but should be recognized as a clue to the presence of this unusual lesion.

Adolescent↗
PubMed2000

Interictal discourse production in temporal lobe epilepsy.

Discourse production was investigated in 16 patients with left-temporal-lobe epilepsy (LTLE) and 17 neurologically normal relatives. Narrative was elicited with the Joanette and Goulet (1989) eight frame "Cowboy" cartoon on three immediately consecutive occasions. Variables of interest were fluency (words/s), speaking time, and word count. While controls produced increasingly concise forms of the story over repetitions, the TLE group became more verbose. Fluency did not not differentiate the groups. These findings suggest that LTLE is associated with macrolinguistic disturbances. The role of capacity limitations and motivational factors in TLE discourse production is discussed.

Adolescent↗