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Biomedical subjects

S F Berkovic

Publications and source records attributed to S F Berkovic.

At least 73 records · Page 4Linked to original sources
PubMed2000

Periventricular nodular heterotopia in patients with filamin-1 gene mutations: neuroimaging findings.

BACKGROUND: The filamin-1 (FLN-1) gene is responsible for periventricular nodular heterotopia (PNH), which is an X-linked dominant neuronal migration disorder. OBJECTIVE: To review the clinical and imaging findings in a series of patients with documented filamin-1 mutations. MATERIALS AND METHODS: A retrospective review of the medical records and MR studies of a series of patients with PNH and confirmed FLN-1 mutations was done. There were 16 female patients (age range: .67-71 years; mean = 28.6) with filamin-1 gene mutations. RESULTS: In six of the patients the same mutation was inherited in four generations in one pedigree. In a second pedigree, a distinct mutation was found in two patients in two generations. In a third pedigree, a third mutation was found in four patients in two generations. The remaining four patients had sporadic de novo mutations that were not present in the parents. Ten patients had seizures, and all patients had normal intelligence. In all 16 patients MR demonstrated bilateral near-continuous PNH. There were no consistent radiographic or clinical differences between patients carrying different mutations. CONCLUSION: Patients with confirmed FLN-1 gene mutations are usually female and have a distinctive MR pattern of PNH. Other female patients with this same MR pattern probably harbor FLN-1 mutations and risk transmission to their progeny. This information is important for genetic counseling.

Adolescent↗
PubMed2000

Does cardiac conduction pathology contribute to sudden unexpected death in epilepsy?

Heart weights have been reported to be increased in those dying suddenly and unexpectedly from epilepsy (SUDEP) and it has been suggested that cardiac pathology including cardiac conduction pathology and coronary artery atheroma may contribute to SUDEP. The purpose of this study was to perform a detailed controlled study of the microscopic pathology of the cardiac conduction system in SUDEP cases, in addition to assessing coronary artery atheroma and other cardiac pathology. The hearts of ten SUDEPs and ten control subjects (no history of epilepsy and a cause of death not primarily cardiac) were examined macroscopically and microscopically by two pathologists blinded to the patient group. Morphological abnormalities of the cardiac conduction system that could have possibly contributed to death were not increased in the SUDEP group (four cases showed such changes in the SUDEP group vs. six in the control). There was no significant difference between the maximal percentage coronary artery stenoses between the two groups and no increased prevalence of other cardiac pathology in the SUDEP group. However, since subtle abnormalities of the conduction system were identified in some of the epileptic deaths, it is still feasible that these may contribute to death by causing cardiac arrhythmia, when associated with apnoea, bradycardia or other cardiac arrhythmia related to an epileptic seizure.

Adolescent↗
PubMed2000

Components of verbal learning and hippocampal damage assessed by T2 relaxometry.

We studied a group of 31 temporal lobe epilepsy patients (25 left, 6 right) with unilateral hippocampal sclerosis evident on magnetic resonance imaging. Single slice T2 relaxation times were acquired for the left and right hippocampi. Principal components analysis of preoperative memory data resulted in two factors that reflect a distinction between arbitrary and semantic forms of verbal recall. The former component correlated with left hippocampal T2 relaxation time, while the latter component did not. This study suggests that variation in left hippocampal integrity is more related to the acquisition of arbitrary associates than semantically structured material, and reinforces the possibility that the left temporal lobe is functionally heterogeneous with respect to memory.

Adolescent↗
PubMed2000

Sudden unexpected death in epilepsy in Victoria.

Sudden unexpected death in epilepsy (SUDEP) refers to sudden unexpected death in patients with epilepsy in whom autopsy fails to reveal an anatomic or toxicological cause of death. The purpose of this study was to examine associated factors and mechanisms relating to SUDEP in Victoria. The study was a retrospective study based on data from questionnaires completed by treating doctors and coronial files including police reports of death, autopsy and toxicology reports. The deaths were of people with epilepsy in Victoria that were referred to the coroner between 1991 and 1997. There were 15,751 coronial autopsies of which 357 had epilepsy and 50 (14%) were SUDEPs. The SUDEP rate was approximately 1 per 3000 epileptics per year. This study suggested the following associations: young age, tonic-clonic seizures, seizure frequency greater than 10/year, duration of epilepsy greater than 10 years, mental retardation, psychiatric disease and alcohol abuse. Antiepileptic drug (AED) compliance was rated by treating doctors as good in 24 cases. One or more postmortem AED drug levels was subtherapeutic in 30 of 50 cases. Only 5 were receiving psychotropic drugs; only 1 of these was receiving more than one of these drugs. A history of recent unusually stressful life event was present in only 4 cases. At least 11 showed evidence of terminal seizure, and the majority of events occurred in sleep. These observations support the hypothesis that seizures are the mechanism of many cases of SUDEP. The associations observed were largely in agreement with previous studies. However, seizure frequency was greater and duration of epilepsy greater than most previous studies. The role of factors such as AED compliance, psychotropic drug prescription and recent unusually stressful life event is less clear. This highlights the need for case-control studies of risk factors for SUDEP.

Adolescent↗
PubMed2000

Intraoperative monitoring to preserve central visual fields during occipital corticectomy for epilepsy.

Photic driving using a flashing strobe light was recorded via intracranial electrodes in two patients with occipital epilepsy being evaluated for surgery. The same technique was used to monitor the visual cortex intraoperatively. Visual evoked potentials (VEPs) were also obtained using the intracranial electrodes in one patient. Preoperative photic driving occurred in a separate location from the cortical areas producing ictal epileptiform activity. VEPs were located in the same site as photic driving. Photic driving was monitored throughout the resection and remained unaffected at the end of each procedure. Postoperative visual field testing in both patients showed preservation of central vision although some reduction in peripheral fields was seen. Intraoperative monitoring of the visual cortex using photic stimulation proved to be a reliable technique for preserving central vision during occipital lobe surgery.

Adult↗
PubMed2000

A new locus for generalized epilepsy with febrile seizures plus maps to chromosome 2.

Generalized epilepsy with febrile seizures plus (GEFS+) is a recently recognized but relatively common form of inherited childhood-onset epilepsy with heterogeneous epilepsy phenotypes. We genotyped 41 family members, including 21 affected individuals, to localize the gene causing epilepsy in a large family segregating an autosomal dominant form of GEFS+. A genomewide search examining 197 markers identified linkage of GEFS+ to chromosome 2, on the basis of an initial positive LOD score for marker D2S294 (Z=4.4, recombination fraction [straight theta] = 0). A total of 24 markers were tested on chromosome 2q, to define the smallest candidate region for GEFS+. The highest two-point LOD score (Zmax=5.29; straight theta=0) was obtained with marker D2S324. Critical recombination events mapped the GEFS+ gene to a 29-cM region flanked by markers D2S156 and D2S311, with the idiopathic generalized epilepsy locus thereby assigned to chromosome 2q23-q31. The existence of the heterogeneous epilepsy phenotypes in this kindred suggests that seizure predisposition determined by the GEFS+ gene on chromosome 2q could be modified by other genes and/or by environmental factors, to produce the different seizure types observed.

Age of Onset↗
PubMed2000

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 in 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.

Epilepsy↗
PubMed2000

The nature and duration of acute concussive symptoms in Australian football.

OBJECTIVE: The purpose of this pilot study was to document the nature and temporal profile of the clinical symptoms of acute sport-related concussion. DESIGN: Prospective cohort study PATIENT POPULATION: A total of 303 elite Australian football players participating in a national competition during a single season. OUTCOME MEASURES: Number and duration of symptoms, digit symbol substitution test (DSST) scores, time of return to play post injury. RESULTS: A total of 23 concussions were recorded over the course of the 20-week football season. No catastrophic head injuries occurred. Headache was the most common symptom and the most persistent, with 40% of players reporting headache symptoms lasting more than 15 minutes. Ten of the players (43%) returned to sport on the day of the injury with the remainder resuming play within 2 weeks. A low likelihood of return to play on the day of injury was found where 3 or more symptoms were present or where the symptoms lasted more than 15 minutes. These findings were significantly correlated with poor DSST performance. CONCLUSIONS: This pilot study suggests that both the number of postconcussive symptoms and their duration may be used as a measure of injury severity and a guide for return to play.

Analysis of Variance↗
PubMed2000

Ictal SPECT and interictal PET in the localization of occipital lobe epilepsy.

PURPOSE: To compare the localizing value of ictal single photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose-positron emission tomography (FDG-PET) in refractory occipital lobe epilepsy. METHODS: Six patients who underwent surgery for refractory epilepsy associated with pathology in the occipital lobe were retrospectively selected from records of the Austin & Repatriation Centre Comprehensive Epilepsy Programme. Interictal SPECT and PET and ictal SPECT were obtained by standard methods. All studies were read by a nuclear medicine expert blinded to clinical data except the diagnosis of epilepsy. RESULTS: Ictal SPECT showed unilateral occipital hyperperfusion in five of six cases often accompanied by temporal lobe hyperperfusion. These patterns were seen in cases with or without magnetic resonance imaging (MRI) abnormality. Interictal SPECT was not localizing in any case, in contrast to PET, which showed occipital hypometabolism in three of five studies. CONCLUSIONS: Ictal SPECT can provide novel localizing data in MRI-negative occipital lobe epilepsy. Interictal PET can provide useful localizing information, but its role in providing novel information was not demonstrated. Interictal SPECT is useful only as a baseline to aid in interpretation of ictal studies.

Adult↗
PubMed2000

Prolactin levels in sudden unexpected death in epilepsy.

PURPOSE: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure. METHODS: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy. RESULTS: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects. CONCLUSIONS: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15-20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure.

Adolescent↗
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↗
PubMed2000

Familial epilepsies: quality of life issues in genetic research.

Recent major advances in understanding the clinical and molecular genetics of epilepsies have come from the twin and family studies conducted to help unravel this complex group of conditions. Analysis of familial epilepsies also provides unique insights into quality of life issues, because genetic and environmental factors are largely controlled in these studies. A brief review of the genetics of epilepsy is presented, with emphasis on quality of life issues from the perspective of the daily lives of patients with familial epilepsies and on issues regarding clinical research in such families.

Epilepsy↗
PubMed1999

Motor cortex localization using functional MRI and transcranial magnetic stimulation.

OBJECTIVE: Congenital brain lesions producing focal seizures may be accompanied by reorganization of the areas responsible for motor and sensory functions within the brain due to a phenomenon that has been termed "neuronal plasticity." This can be studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Using either method, the motor cortex can be localized noninvasively, but to date there have been few studies correlating the level of agreement between the two techniques. METHODS: We used fMRI and TMS to localize the motor cortex in a young woman with intractable focal seizures, congenital left arm weakness, and a dysplastic right hemisphere on MRI. RESULTS: There was excellent agreement in the localization of motor representation for each hand. Both were predominantly located in the left hemisphere. fMRI also showed an area of posterior activation in the right hemisphere, but there was no evidence of descending corticospinal projections from this site using TMS, direct cortical stimulation, and Wada testing. CONCLUSIONS: Functional MRI (fMRI) and transcranial magnetic stimulation (TMS) were successfully used to localize cortical motor function before epilepsy surgery. Each technique demonstrated migration of motor function for the left hand to the left motor cortex. After resection of the dysplastic right precentral gyrus there was no permanent increase in weakness or disability. The two techniques are complementary; fMRI indicates all cortical areas activated by the motor task, whereas TMS identifies only those areas giving rise to corticospinal projections.

Adult↗
PubMed1999

Cortical excitability and recovery curve analysis in generalized epilepsy.

Seven untreated patients with idiopathic generalized epilepsy were studied with recovery curve analysis using transcranial magnetic stimulation and compared with 16 controls. Patients had a shorter period of inhibition of the test response following a conditioning stimulus and demonstrated a period of increased facilitation of the test response at interstimulus intervals of 200 to 300 msec, which was similar to the mean interdischarge interval of spike-wave activity on EEG. This provides further evidence of cortical hyperexcitability in idiopathic generalized epilepsy.

Adolescent↗