Biomedical subjects

S F Berkovic

Publications and source records attributed to S F Berkovic.

At least 163 records · Page 9Linked to original sources

PubMed1994

P3 latency jitter assessed using 2 techniques. I. Simulated data and surface recordings in normal subjects.

Latency variability measurement using cross-correlational techniques has the drawback of alignment to background noise not related to ERP activity. We compared latency jitter estimation in simulated and real P3 recordings using Woody's algorithm and a non-cross-correlational technique, the maximum likelihood technique (MLT). Simulated ERPs (with introduced latency jitter) were generated using either a 1/2 cycle 2 Hz sine wave or an averaged P3 ERP with 1 of 3 added noise types in 5 signal to noise ratios (SNRs): (i) white noise; (ii) a 10 Hz sine wave; (iii) a 7.5 Hz sine wave. Jitter measurement accuracy was assessed using mean square error (MSE) for 1 iteration of the Woody method and each of 4 iterations of the MLT. Lowest MSEs occurred for higher SNRs and 1 iteration of the MLT. The MLT and Woody method were applied to P3 ERPs of 13 subjects with SNRs greater than 0.4 P3 latency jitter was significantly lower for the MLT. Latency jitter (both methods) did not differ between homologous electrodes and was highest in posterior electrodes. In the latency corrected ERP data of subjects with persistent alpha activity periodic components occurred in the Woody corrected average (not seen in the conventional or the MLT corrected averages). Our data indicate that the MLT is the more accurate method for determining latency jitter.

Adult↗

PubMed1994

P3 latency jitter assessed using 2 techniques. II. Surface and sphenoidal recordings in subjects with focal epilepsy.

We compared the latency variability in auditory P3s of 13 subjects with unilateral temporal lobe epilepsy (TLE) to that of normal controls. We predicted that increased latency jitter would occur in TLE subjects, particularly on the epileptic side. ERPs were recorded from scalp and sphenoidal sites relative to a balanced non-cephalic reference. Signal-to-noise ratios (SNRs) were calculated for each subject. Data were excluded if SNRs fell below 0.4. P3 latency jitter was estimated using 2 methods: Woody's algorithm and the maximum likelihood technique (MLT), a novel method of jitter assessment. SNRs were significantly higher in controls and were maximal posteriorly for both groups. P3 peak amplitude was significantly smaller in TLE subjects at temporal sites. Latency jitter (MLT method) was greatest in posterior sites and mirrored the jitter profiles of controls. Latency jitter was significantly higher in TLE subjects in bilateral frontal and temporal sites, but was not higher on the side of the focus and could not be attributed to lower SNRs. The increased bilateral latency jitter in these patients may be related to effects of anticonvulsants or the more extensive nature of the underlying epileptic disorder.

Adolescent↗

PubMed1994

Interictal language fluency in temporal lobe epilepsy.

Mild language production difficulties, particularly in confrontation naming, have been documented previously in patients with left temporal lobe epilepsy (LTLE). These difficulties, however, do not seem to be reflected in the conversational speech of these patients. In order to compare speech fluency in patients with left and right temporal lobe epilepsy (RTLE) experimentally, we studied global pause-to-speech ratios in patients with unilateral temporal lobe epilepsy, using cases with primary generalized epilepsy (PGE) as controls. We hypothesized that left-sides cases would exhibit longer pause durations than right-sided cases. Speech samples were elicited by asking subjects to describe five different New Yorker cartoons, with three repetitions of each description. Phonation was converted to graphic output, and pauses between 200 ms and 4000 ms were summated and divided by total phonation time. This measure did not discriminate significantly between the groups, although the LTLE group tended to pause longer than the RTLE or PGE groups. Increased variability in pause duration in the LTLE group during cycle 1 suggested that some individuals with LTLE are vulnerable to disruption when planning demands are high. A post hoc correlational analysis showed that variation in fluency was primarily explained by orthographically-based lexical retrieval, suggesting that individual differences in fluency are related to limitations in a high-level capacity relevant to the production of speech. It is unlikely that such limitations are specific to LTLE.

Adult↗

PubMed1994

Heterogeneity in the phenotypic expression of the mutation in the mitochondrial tRNA(Leu) (UUR) gene generally associated with the MELAS subset of mitochondrial encephalomyopathies.

BACKGROUND: Point mutations in the mitochondrial (mt) genome underlie a number of neurological disorders. Some are well defined including the myoclonus epilepsy ragged red fibre syndrome (MERRF) and the mitochondrial encephalopathy lactic acidosis stroke like episode syndrome (MELAS). However, other clinical phenotypes are less distinctive and mitochondrial studies are often included in the workup in complex neurological syndromes of uncertain aetiology. AIMS: We investigated 27 consecutive patients with varied clinical phenotypes referred to our laboratory for mtDNA studies to determine the incidence of recognised point mutations in a patient group with a range of phenotypes including many where mt disease was possible but did not fall into a classical syndrome. METHODS: The recognised point mutations were detected by amplification of the appropriate DNA fragment by PCR followed by restriction-endonuclease digestion of the normal and mutant species. RESULTS: The A-G base substitution mutation at nucleotide (nt)3243 in the tRNA(Leu) gene of mtDNA which is present in the majority of cases of MELAS syndrome, was detected in four cases, only one of whom had typical MELAS symptoms. Their clinical manifestations ranged from mild deafness to a mixture of chronic progressive external ophthalmoplegia symptoms (CPEO) and stroke like episodes. The nt3243 mutation was also identified in one of seven mtDNA deletion negative CPEO cases. CONCLUSIONS: The presentation of the mtDNA mutation at nt3243 appears therefore to be quite variable with some mild phenotypes as well as severe phenotypes observed. In general, the chance of finding a mitochondrial point mutation in a patient with an atypical clinical phenotype is small.

Adult↗

PubMed1994

Functional neuroimaging with SPECT in children with partial epilepsy.

Single-photon emission computed tomography (SPECT) is being used increasingly in the investigation of children with intractable partial seizures. SPECT imaging of regional cerebral blood flow with 99mTc-hexamethylpropylene amine oxime, iodinated radiopharmaceuticals, and 133Xe typically reveals decreased cortical perfusion interictally and increased cortical perfusion ictally in the region of the epileptic focus. Studies in both adults and children indicate significantly greater sensitivity and specificity with ictal injection of radiopharmaceutical, with interictal SPECT not infrequently revealing nonlocalizing or falsely localizing information. Recent SPECT studies employing iodinated neuroreceptor ligands report altered receptor binding in the region of the epileptic focus, providing insight into the underlying neuropharmacology of partial epilepsy. SPECT has an established role in the presurgical localization of seizure foci in children with intractable partial seizures and may be a useful modality to study the functional anatomy and clinical semiology of partial seizures in childhood.

Adult↗

PubMed1994

Parietal lobe epilepsy: clinical features and seizure localization by ictal SPECT.

We studied clinical and ictal single-photon emission computed tomography (SPECT) features in 14 patients with parietal lobe epilepsy, nine of whom had structural parietal lobe lesions. Thirteen patients had simple partial seizures of somatosensory (eight), psychic (four), and motor (nine) types. Complex partial seizures (CPS) occurred in seven patients; six were psychoparetic (prominent staring, relative immobility) and one had hyperkinetic activity. Seizures lasted 7 to 110 seconds; 99mTc-HMPAO (hexamethylpropylene amine oxime) was injected ictally, 7 to 89 seconds from seizure onset and 0 to 74 seconds (mean, 21.0 +/- 24.4 seconds) before seizure termination. Ictal SPECT demonstrated focal areas of parietal hyperperfusion in all 14 cases and corresponded with sites of the structural lesions. Parietal hyperperfusion was anterior in eight, posterior in four, and diffuse in two. Quantitative analysis revealed increases in parietal side-to-side perfusion ratios on ictal compared with interictal scans of 11 to 51% (mean, 25.5 +/- 14.4%). Ictal SPECT localization correlated with two main clinical seizure patterns: an anterior syndrome characterized by sensorimotor manifestations and a posterior syndrome characterized by CPS of the psychoparetic type. Ictal SPECT is helpful for localization of parietal seizures. Parietal hyperperfusion is discrete and short-lived, demanding true ictal injections for diagnostic studies.

Adolescent↗

PubMed1994

Rey figure distortions reflect nonverbal recall differences between right and left foci in unilateral temporal lobe epilepsy.

Recall of the Rey Complex Figure (RCF) by patients with left (N = 26) or right (N = 18) temporal lobe epilepsy was scored in terms of the qualitative approach developed by Loring, Lee, and Meador. Patients with right temporal lobe epilepsy exhibited significantly more qualitative errors on recall of the RCF than patients with left temporal foci, whereas standard RCF scores failed to differentiate the groups. A linear discriminant function analysis showed that 66% of patients were correctly classified into lateral focus groups on the basis of qualitative scores, with a sensitivity of 50% and specificity of 77%. Although unsuitable for clinical use in its present form, the qualitative approach appears to be a promising one. The findings offer support for the position that some aspects of nonverbal memory are critically dependent on the integrity of the right temporal lobe. The implications of this for reorganization of cerebral representation are examined.

Journal Article↗

PubMed1993

Effects of angiotensin II on dopamine and serotonin turnover in the striatum of conscious rats.

This study was designed to evaluate the functional significance of angiotensin II (Ang II) receptors identified by previous receptor autoradiography studies to be located presynaptically on terminals of dopaminergic neurones projecting to the striatum. Microdialysis was performed in the striatum of conscious freely moving rats and dopamine and serotonin metabolites measured by HPLC with electrochemical detection. During perfusion with artificial CSF, the major extracellular dopamine metabolite identified was DOPAC with smaller concentrations of HVA. When Ang II (1 microM) was introduced into the dialysis perfusion medium, DOPAC output increased markedly, peaking at 219%, and returned to control with vehicle perfusion during the recovery period. This increase in DOPAC output with Ang II was completely blocked by co-administration of the AT1 selective antagonist, Losartan (1 microM). Administration of Losartan alone led to a significant (16%) depression of DOPAC output relative to vehicle, suggesting that dopamine release is under a tonic facilitatory influence of Ang II via the AT1 receptor subtype. Parallel, but smaller changes were seen with HVA outputs. During Ang II perfusion the output of HVA was elevated 34-79% of that in vehicle-treated rats and this effect was completely abolished by concomitant administration of Losartan. As was observed with DOPAC output, administration of Losartan alone led to a 13-24% depression of HVA output compared to vehicle perfusion. When nomifensine (10 microM) was included in the infusion fluid, dopamine was clearly measurable. Ang II perfusion increased the levels of dopamine to 225%. Values returned towards baseline during the recovery period. Ang II administration also increased (by 15% and 55%) the levels of the major serotonin metabolite, 5HIAA.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Life-threatening focal status epilepticus due to occult cortical dysplasia.

OBJECTIVE: Neuronal migration disorders are usually, but not necessarily, demonstrated by magnetic resonance imaging. Preoperative suspicion of these anomalies in the presence of normal magnetic resonance studies has important practical implications. This study delineates some clinical features that permit early suspicion of focal cortical dysplasia localized in the central and precentral regions. DESIGN: In a retrospective case series, we studied the clinical presentation of four consecutive patients with normal preoperative magnetic resonance images in whom focal cortical dysplasia was found in the surgical specimen. SETTING: Patients were seen in three referral centers specializing in epilepsy surgery. PATIENTS: Four patients (three female), between the ages of 4 and 21 years, had intractable partial seizures leading to resective brain surgery. INTERVENTION: Three patients had corticectomies in the central (two patients) or frontal (one patient) regions. One underwent an en bloc resection of the central area after two unsuccessful corticectomies and cortical transection. RESULTS: Three patients presented with life-threatening focal motor status epilepticus necessitating intubation, and one had epilepsia partialis continua. All had had seizures previously, and the attacks progressed to intractability after 1 1/2 to 3 years. Surgery led to control of the seizures, but only two patients became seizure free (mean follow-up, 15.7 months). All but one developed a postoperative deficit, which eventually improved. CONCLUSIONS: Focal cortical dysplasia should be suspected when life-threatening focal motor status epilepticus or epilepsia partialis continua occur in children or young persons without another obvious cause. Normal magnetic resonance studies do not exclude neuronal migration disorders.

Adolescent↗

PubMed1993

Magnetic stimulation of the brain in generalized epilepsy: reversal of cortical hyperexcitability by anticonvulsants.

Observations on experimental models suggest that diffuse cortical hyperexcitability is an important abnormality in the generalized epilepsies. We used the threshold for transcranial magnetic stimulation as an index of motor cortical excitability in 89 neurologically normal control subjects and 56 patients with idiopathic generalized epilepsy (20 untreated and 36 chronically treated with anticonvulsants). Magnetic stimulation was repeated in 10 patients after valproate monotherapy had been commenced and in 23 control subjects. The threshold intensity was significantly lower in the untreated patients (46 +/- 5% [mean +/- 95% confidence interval]) than in the control subjects (56 +/- 2%). Treated patients had significantly higher thresholds (64 +/- 4%) than did untreated patients and control subjects. A significant increase in threshold intensity (8 +/- 2%) occurred in patients retested after starting valproate; there was no significant change in retested control subjects (-1 +/- 2%). Threshold intensity was positively correlated with plasma valproate levels (rs = 0.37). The findings suggest that cortical excitability is increased in idiopathic generalized epilepsy and is reduced following anticonvulsant treatment. Transcranial magnetic stimulation is of use in examining the pathophysiology of generalized epilepsy. Furthermore, changes in threshold intensity in response to anticonvulsant treatment may prove useful in guiding therapy.

Adolescent↗

PubMed1993

The influence of changes in the intensity of magnetic stimulation on coil output.

We measured the peak voltage induced in a sensing loop by a Magstim 200 magnetic stimulator. Coil output varied little for repeated stimulation at the same intensity over a wide range of coil output. In contrast, the first stimulus immediately after a change in intensity was of larger amplitude and showed greater variability than subsequent stimuli. The effect was seen for changes in intensity of 5% and 60% and was greater for reductions than for increases in stimulation intensity. Stimulation immediately after a reduction in intensity from 100% to 40% resulted in peak induced voltages as high as those recorded for repeated stimulation at 43% of maximum coil output. Increased coil output following changes in stimulation intensity may affect measurement of the threshold old for motor cortical stimulation. The effect of a change in intensity could be minimized by delaying stimulation for at least 30 s or discarding the first stimulus after the change.

Brain↗

PubMed1993

Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects.

This study retrospectively investigated the effect of left (LHS) versus right (RHS) hippocampal sclerosis on verbal memory, measured by means of the Paired Associate Learning and Logical Memory subtests of the Wechsler Memory Scale (WMS) administered as part of a routine preoperative assessment. Patients were selected for the presence of unilateral hippocampal sclerosis by means of preoperative magnetic resonance imaging (MRI) and postoperative neuropathology. The LHS patients (n = 20) were significantly worse on paired associate learning than RHS patients (n = 18), the performance of RHS patients being consistent with normative standards. In contrast, no laterality effect was seen on the immediate and delayed recall of passages; the evidence suggests that both groups performed at a mildly impaired level. It was suggested that the laterality of verbal memory is conditional upon specific task demands in patients with damage to mesial temporal structures.

Adult↗

PubMed1993

Progressive myoclonus epilepsies: clinical and genetic aspects.

The progressive myoclonus epilepsies (PMEs) are a group of rare genetic disorders previously shrouded in nosological confusion. Recent advances have clarified the features of these disorders and provided a rational approach to diagnosis. The major causes of PME are now known to be Unverricht-Lundborg disease, myoclonus epilepsy ragged-red fiber (MERRF) syndrome, Lafora disease, neuronal ceroid lipofuscinoses, and sialidoses. Over the past 3 years, a series of molecular genetic findings have further refined the understanding of the PMEs. The specific mutation responsible for many cases of MERRF has been identified, and the genes for Unverricht-Lundborg disease and for juvenile neuronal ceroid lipofuscinosis have been linked to chromosomes 21 and 16, respectively. Although the PMEs are among the rarest of the inherited epilepsies, because of molecular genetic discoveries they may soon be the best understood at the neurobiologic level.

Adolescent↗

PubMed1993

Localised neuronal migration disorder and intractable epilepsy: a prenatal vascular aetiology.

Localised neuronal heterotopias are an increasingly recognised cause of intractable focal epilepsies. The aetiology of these circumscribed disorders of neuronal migration is often unknown although in some instances proximity to areas of prenatal infarction suggests that severe ischaemia was responsible. A patient is described with intractable complex partial seizures associated with heterotopic grey matter and cerebral hypoplasia confined to the territory of the left posterior cerebral artery; the left hippocampus was spared. Angiography showed a normal left anterior choroidal artery but a hypoplastic left posterior cerebral artery, implicating prenatal ischaemia without frank infarction as the aetiology of the malformation.

Adult↗

PubMed1993

Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures.

The results of a multicentre, randomised, double-blind, placebo controlled, crossover trial of lamotrigine as add-on therapy in patients with partial seizures poorly controlled by established antiepileptic drugs (AEDs) are presented. The study consisted of two 12 week treatment periods each followed by a four week washout period. During the lamotrigine treatment phase, patients received 150 mg or 300 mg daily dose depending on their concomitant AEDs to achieve concentrations in the range 1-3 mg/L. Forty one patients were entered at four centres and all patients entered completed the study. There was a highly significant (p < 0.001) decrease in total seizure counts on lamotrigine compared with placebo. Overall, 22% of patients experienced at least a 50% reduction in the total numbers of all seizures types on lamotrigine, compared with none on placebo. When the total numbers of partial seizures (simple and complex partial) were analysed there was also a significant (p < 0.05) reduction in seizure counts on lamotrigine compared with placebo. When total numbers of secondarily generalised seizures were compared the trend for a reduction in this seizure type did not achieve significance (0.05 < p < 0.1). Concomitant AED plasma concentrations were virtually unchanged. It is concluded that lamotrigine is an effective AED in the treatment of therapy-resistant partial seizures.

Anticonvulsants↗

PubMed1993

Frontal lobe epilepsy: clinical seizure characteristics and localization with ictal 99mTc-HMPAO SPECT.

We evaluated ictal 99mtechnetium hexamethyl propylene-amine-oxime single-photon emission computed tomography (SPECT) in 22 children with electroclinical features of frontal lobe epilepsy (FLE). Ictal SPECT demonstrated unilateral frontal hyperperfusion in 20 of 22 children (91%) (one lobar, two frontocentral, six dorsolateral, six frontopolar, three orbitofrontal, one medial frontal, and one insula), concordant with electroclinical lateralization in 19 of 20 (95%). Hyperperfusion was evident in the ipsilateral basal ganglia in 16 of 22 (73%) and the contralateral cerebellum in 14 of 22 children (64%). Interictal SPECT showed unilateral, localized frontal hypoperfusion concordant with electroclinical lateralization in only two of 22 children (9%). Ictal SPECT localization to the frontocentral, media frontal, or dorsolateral regions was associated with asymmetric tonic posturing, contralateral head/eye deviation, and unilateral clonic jerking (p < 0.01). Ictal SPECT localization to the frontopolar or orbitofrontal regions was associated with vocalization, hyperventilation, truncal flexion, and complex gestural automatisms (p > or = 0.05). Ictal SPECT has the potential to (1) localize seizures in patients with intractable FLE, and (2) advance understanding of the in vivo anatomico-clinical relationships of frontal lobe seizures.

Adolescent↗

PubMed1993

Twin birth is not a risk factor for seizures.

There is a belief that perinatal factors are a major cause of epilepsy. We studied a community-based sample of twins, a group with a marked excess of adverse perinatal events. The observed number of non-twin siblings with seizures did not differ from that predicted by the age-specific cumulative incidence rate of seizures (4.2% at age 10 years) in the twins. The types of epilepsies in the twins were largely benign and self-limited and not those associated with brain damage. Zygosity, birth order, and birth weight did not predict affected status. Within affected sibships, the frequency of seizures in co-twins of dizygotic probands (9%) was not different from the frequency in non-twin siblings (12%) but was much less than the frequency in co-twins of monozygotic probands (38%; p < 0.001), reflecting a major genetic component to certain epilepsies. These data show that twins do not have an increased risk of seizures and strongly suggest that perinatal factors have little bearing on the etiology of the common epilepsies in the community.

Adolescent↗

PubMed1993

Cortical hyperexcitability in progressive myoclonus epilepsy: a study with transcranial magnetic stimulation.

In progressive myoclonus epilepsy (PME), responses to afferent input are frequently abnormal. It is unclear whether the abnormality lies at the cortical, subcortical, or segmental level. To obtain evidence for an exaggerated effect on motor cortical excitability, we used peripheral nerve and transcranial magnetic stimulation in controls and subjects with idiopathic generalized epilepsy and PME. Mean threshold intensity was higher in those with idiopathic generalized epilepsy and PME than in controls, probably as a result of anticonvulsant treatment. A long-latency response to peripheral stimulation and an exaggerated facilitatory effect of peripheral stimulation on the motor evoked potential was present in subjects with PME. Latency differences between the late responses in the upper and lower limbs provided evidence against a segmental reflex and implicated rapidly conducting fibers in the spinal cord. Both the late response and the facilitatory effect had onset latencies consistent with a transcortical pathway, suggesting an exaggerated effect of afferent input on motor cortical excitability in PME.

Adaptation, Physiological↗