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Rightward attentional bias and left hemisphere dominance in a cue-target light detection task in a callosotomy patient.

Six normal subjects and a callosotomized man with a prefrontal lesion, mostly on the right side, were tested in a reaction time (RT) task involving a key-pressing response to an extrafoveal light target preceded by an extrafoveal light cue. Cues and targets were presented along the horizontal meridian at 4 degrees and 12 degrees on the right and left of fixation. Fixation was maintained throughout each trial. The cue signalled the occurrence of the target within a time window extending from 200 to 4000 misec from the cue, but did not predict target location. Normal controls responded faster to medial than to lateral targets in both fields, but showed no between-field difference, and their RT was not affected by cue location. Furthermore, they showed the so-called 'ipsilateral inhibition' or 'inhibition of return' effect, their RT being longer when cues and targets occurred in the same field than when they occurred in opposite fields. The RT of the callosotomized subject showed a left-right gradient for both cue location and target location, being longest for the leftmost location and shortest for the right locations. In addition, he showed a significant advantage for the right hand regardless of cue and target location, as well as a consistent ipsilateral inhibition in the left field, whereas in the right field there was ipsilateral inhibition only at the two longest stimulus onset asynchronies. These results suggest that, at least under these experimental conditions, there was a rightward orientational bias which reflected the taking over of the control of performance by the left hemisphere. This attentional bias was reminiscent of that seen in patients with hemi-inattention from right hemisphere damage, although the callosotomized patient showed no sign of such hemi-inattention in routine clinical tests. On the basis of several considerations the rightward bias could be attributed to the callosal interhemispheric disconnection rather than to the right prefrontal lesion.

Adult↗

Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial.

BACKGROUND: Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures. METHODS: At a residential school with on-site medical facilities 42 young people with severe epilepsy were enrolled. Continuous seizures of more than 5 min duration were randomly treated with buccal midazolam or rectal diazepam. If the seizure did not stop within 10 min additional medication chosen by the attending physician was administered. We monitored oxygen saturation and blood pressure for 30 min after treatment. The main outcome measures were efficacy, time from arrival of the nurse to drug administration, time from drug administration to end of seizure, and incidence of adverse cardiorespiratory events. FINDINGS: Buccal midazolam was used to treat 40 seizures in 14 students, and rectal diazepam 39 seizures in 14 students. Midazolam stopped 30 (75%) of 40 seizures and diazepam 23 (59%) of 39 (p=0.16). The median time from arrival of the nurse to administration of medication was 2 min. Time from administration to end of seizure did not differ significantly between the two treatments. No clinically important adverse cardiorespiratory events were identified in the two groups. Buccal midazolam was universally acceptable to the nursing and care staff. INTERPRETATION: Buccal midazolam is at least as effective as rectal diazepam in the acute treatment of seizures. Administration via the mouth is more socially acceptable and convenient and may become the preferred treatment for long seizures that occur outside hospital.

Administration, Buccal↗

Evolution of brain glucose metabolism with age in epileptic infants, children and adolescents.

During the first years of life, the human brain undergoes repetitive modifications in its anatomical, functional, and synaptic construction to reach the complex functional organization of the adult central nervous system. As an attempt to gain further insight in those maturation processes, the evolution of cerebral metabolic activity was investigated as a function of age in epileptic infants, children and adolescents. The regional cerebral metabolic rates for glucose (rCMRGlc) were measured with positron emission tomography (PET) in 60 patients aged from 6 weeks to 19 years, who were affected by complex partial epilepsy. They were scanned at rest, without premedication, in similar conditions to 20 epileptic adults and in 49 adult controls. The distribution of brain metabolic activity successively extended from sensorimotor areas and thalamus in epileptic newborns to temporo-parietal and frontal cortices and reached the adult pattern after 1 year of age. The measured rCMRGlc in the cerebral cortex, excluding the epileptic lesions, increased from low values in infants to a maximum between 4 and 12 years, before it declined to stabilize at the end of the second decade of life. Similar age-related changes in glucose metabolic rates were not observed in the adult groups. Despite the use of medications, the observed variations of rCMRGlc with age in young epileptic humans confirm those previously described in pediatric subjects. These metabolic changes are in full agreement with the current knowledge of the synaptic density evolution in the human brain.

Adolescent↗

Historical criteria that distinguish syncope from seizures.

OBJECTIVES: We prospectively sought evidence-based criteria that distinguished between seizures and syncope. BACKGROUND: Loss of consciousness is usually due to either seizures or syncope. There are no evidence-based historical diagnostic criteria that distinguish them. METHODS: A total of 671 patients with loss of consciousness completed a 118-item historical questionnaire. Data sets were complete for all subjects. The data set was randomly divided into two equal groups. The contributions of symptoms to diagnoses in one group were estimated with logistic regression and point scores were developed. The accuracy of the decision rule was then assessed using split-half analysis. Analyses were performed with and without inclusion of measures of symptom burden, which were the number of losses of consciousness and the duration of the history. The scores were tested using receiver-operator characteristic analysis. RESULTS: The causes of loss of consciousness were known satisfactorily in 539 patients and included seizures (n = 102; complex partial epilepsy [50 patients] and primary generalized epilepsy [52 patients]) and syncope (n = 437; tilt-positive vasovagal syncope [267 patients], ventricular tachycardia [90 patients] and other diagnoses such as complete heart block and supraventricular tachycardias [80 patients]). The point score based on symptoms alone correctly classified 94% of patients, diagnosing seizures with 94% sensitivity and 94% specificity. Including symptom burden did not significantly improve accuracy, indicating that the symptoms surrounding the loss of consciousness accurately discriminate between seizures and syncope. CONCLUSIONS: A simple point score of historical features distinguishes syncope from seizures with very high sensitivity and specificity.

Case-Control Studies↗

Rapid infusion of sodium valproate in acutely ill children.

The purpose of this study was to investigate the clinical safety of sodium valproate and total and unbound valproic acid plasma concentrations after rapid infusion in hospitalized, acutely ill children. Four children (5-15 years) completed the study. Sodium valproate doses (8.3-15.4 mg/kg) were administered in <or=15 minutes. No clinically significant changes in vital signs were observed nor were there any significant adverse events. Both total and unbound valproic acid concentrations were higher at 0.5 hour than at pre-infusion or 6 hours after infusion. Rapid administration of valproate to acutely ill patients can be done safely. Unbound valproic acid concentrations in acutely ill as compared with relatively healthy epilepsy patients were higher and could not be predicted based on their total pre-infusion valproic acid concentrations.

Acute Disease↗

A double-blind, placebo-controlled trial of tiagabine given three-times daily as add-on therapy for refractory partial seizures. Northern European Tiagabine Study Group.

In a multicentre, double-blind, parallel-group, placebo-controlled trial, a three-times daily regimen of tiagabine was evaluated as add-on therapy in 154 adult patients with refractory partial seizures. A total of 77 patients were randomised to treatment in each arm. Tiagabine HCl was titrated from an initial dose of 12-30 mg/day over 4 weeks. During the 12-week fixed-dose period, there was a significant reduction in the median 4-weekly seizure rate for all partial seizures and simple partial seizures (P < 0.05 in each case). Furthermore, the proportion of patients with a reduction of 50% or more in all partial seizures was higher in the tiagabine group than in the placebo group (14 versus 6%), though the difference did not achieve statistical significance. The difference with respect to simple partial seizures was significant (21 versus 6%, P < 0.01). The percentage of patients achieving an increase of at least 50% in the proportion of days free of all partial seizures was significantly greater in the tiagabine group compared to placebo (14 versus 4%, P<0.01). Tiagabine did not appear to influence the plasma concentrations of other concomitant antiepileptic drugs and was generally well tolerated, with most drug-related adverse events being mild or moderate in severity. The most common adverse events were dizziness, asthenia, headache and somnolence. Adverse event incidence was similar between tiagabine and placebo groups, except for dizziness which was more common with tiagabine (29 versus 10%, P < 0.01). Tiagabine had no significant effects on laboratory tests or vital signs. The present study shows that tiagabine, at a dose of 10 mg administered three-times daily, which is at the lower end of the usual recommended dose range (30-50 mg/day, tiagabine base), is generally well tolerated and demonstrates efficacy for the treatment of refractory partial seizures.

Adolescent↗

[Indications for emergency EEG. Focal neurologic deficits and partial epileptic seizures in adults].

A focal neurological deficit is defined as the clinical expression of a structural or functional, transient or permanent abnormality that can be ascribed to a particular brain region. In that context, the indications of an EEG as part of the emergency management may be summarized as follows: i) The EEG in not indicated for the diagnostic, prognostic or therapeutic management of transient ischemic attacks (TIA) or migraine; ii) The possible prognostic value of EEG during the acute phase of stroke has not yet been validated; iii) In partial epileptic seizures, especially complex partial epilepsy, the EEG is useful but not always indispensable for diagnosis. Its therapeutical and prognostic implications are still uncertain. Lastly, EEG is an absolute indication as part of the emergency management of focal deficits in a febrile context, where its diagnostic and prognostic value are unequaled.

Adult↗

The anticonvulsant effect of citalopram as an indirect evidence of serotonergic impairment in human epileptogenesis.

Some evidence would indicate that a serotonergic deficit may be involved in epileptogenesis. A preliminary trial of citalopram, a selective inhibitor of serotonin reuptake, was carried out. Citalopram 20mg/day was given to 11 non-depressed patients with poorly controlled epilepsy as an add on treatment with an open label design for 8-10 months. The median seizure frequency dropped by 55.6% in the whole group, with nine patients improving by at least 50%. No adverse reactions occurred with the exception of mild drowsiness. There were no changes of post-treatment as compared to pre-treatment AED serum concentrations. Although controlled studies are required to confirm the anticonvulsant effect of citalopram, these findings may be regarded as an indirect evidence of serotonergic impairment in human epileptogenesis.

Adult↗

What people with epilepsy want from a hospital clinic.

A questionnaire was sent to 511 patients with epilepsy who were being reviewed at the clinics of two consultant neurologists. The questionnaire asked 19 questions about seizure type and how the diagnosis was given. It also asked how much information was given about the disease and advice about living with it. There were also questions about counselling and preference for hospital or community care. Over 96% returned the questionnaire. About one third said they were not told what epilepsy was, over 90% wanted more information about the disease, and about three quarters felt they had not been given enough information about the side-effects of antiepileptic drugs. Over 60% wanted to talk to someone other than a consultant about epilepsy, the most frequent person requested being a specialist nurse. Despite this, three quarters wanted to continue to attend the hospital clinic and 89% were generally satisfied with their hospital management. This survey has highlighted a number of shortcomings in the structure of our clinics. It should be possible to correct them by providing more structured information and having a nurse specialist available.

Adaptation, Psychological↗

'Phantom' typical absences, absence status and experiential phenomena.

We present a case of mild typical absences (phantom absences) culminating in absence status and generalized tonic-clonic seizures. The patient has recorded his experience during an episode of absence status and provides a rare insight into a mind temporarily clouded by whirling thoughts and muffled responses. This case is important as it demonstrates the pitfalls which may hinder the diagnosis of this unusual condition.

Adult↗

Epileptic seizures and infantile states: some thoughts from psychodynamic therapy.

A brief introduction to psychoanalytic thinking around epileptic seizures is given. It is notable how little attention has been paid by psychoanalysis to the psyche-soma links present in epilepsy. The psyche-soma world of the early infant is outlined, along with the impact of impingements on this fragile world. It is postulated that for certain individuals with epilepsy, the seizure state may generate a regression to an earlier developmental state of being involving a change in emotional state and the emergence of unconscious phantasies. Single case study material from the psychodynamically orientated art therapy of 'Gordon', a man with epilepsy and learning disabilities, is used to illustrate and support this hypothesis. This work took place in a specialized centre for epilepsy.

Adult↗

Isolated ataxia as an idiosyncratic side-effect under gabapentin.

Gabapentin has been accepted worldwide as a novel antiepileptic drug with a favourable tolerability profile. However, movement disorders have been reported previously as rare side-effects in individual patients. We report on two patients who developed isolated severe ataxia under low-dose gabapentin which resolved abruptly after discontinuation of the drug. This side-effect probably resembled a rare idiosyncratic adverse reaction. We propose the gabapentin-specific neuronal binding site which has a high density in the cerebellum as a possible mechanism of action and suggest that the initiation of gabapentin requires caution if pre-existing cerebellar function impairment is evident.

Acetates↗

Topiramate-induced metabolic acidosis: report of two cases.

Two children who presented with symptomatic metabolic acidosis after being put on topiramate (TPM) are reported. The first patient was an 11-year-old male with refractory complex partial epilepsy who was put on TPM for 13 months. He developed hyperventilation 1 week after increasing the dose to 300 mg/day. Arterial blood gas revealed hyperchloraemic metabolic acidosis with partial respiratory compensation: pH 7.36, PCO2 27.2 mmHg, bicarbonate 14.9 mEq/L, base excess -8.9 mmol/L. Hyperventilation and acidosis resolved after administration of sodium bicarbonate and reduction of the dose of TPM. The second patient was a female who developed increasing irritability at age 16 months and 21 months, each time associated with introduction of TPM and resolved promptly upon withdrawal of the drug. Venous blood gas taken during the second episode revealed pH 7.34, PCO2 37.4 mmHg, bicarbonate 20.4 mEq/L, base excess -4.2 mmol/L. The predominant mechanism of TPM-induced hyperventilation involves inhibition of carbonic anhydrase at the proximal renal tubule, resulting in impaired proximal bicarbonate reabsorption. The occurrence of hyperpnoea or mental status change in any patient who is on TPM should prompt an urgent blood gas sampling, with correction of the acid-base disturbances accordingly.

Acidosis↗

Topiramate in intractable childhood onset epilepsy--a cautionary note.

OBJECTIVES: To study the effectiveness and safety of topiramate in clinical practice, for a group of patients with childhood onset epilepsy. METHODS: All patients treated with topiramate at the three study centers between November 1995 and December 31, 1997 were analyzed retrospectively, using a standardized study protocol. Data were gathered on demographic features, seizures response and medication related adverse events. RESULTS: Eighty-seven patients were treated with topiramate. Over 90% seizure reduction was achieved in 8 (9%) patients, 50%-90% in 21 (24%), < 50% in 54 (62%) patients. Four patients (5%) had a deterioration in seizure control. Adverse events required topiramate discontinuation in 36 (41%). Of these 27 (31%) complained of unacceptable cognitive dulling. The rate of dose escalation and final dose in mg/kg were similar in those who remained on topiramate and those who were intolerant because of cognitive side effects. CONCLUSIONS: Although topiramate resulted in > 50% seizure reduction in 29 (33%) of this group of patients with difficult epilepsy, its usefulness was limited by a high incidence of adverse effects. Adverse events prevented ongoing therapy for 36 (41%) and cognitive dulling resulted in topiramate discontinuation by 27 (31%) of the group.

Adolescent↗

Properties of advanced headmodelling and source reconstruction for the localization of epileptiform activity.

During the last decade multiple work has been done to determine the sources of epileptiform activity by means of dipole source localization based on recordings of the magnetoencephalogram (MEG) or the electroencephalogram (EEG). The actual available advanced volume conductor models and the multiple source reconstruction by regularization may give new impulse to EEG based source analyses in epilepsy patients. This study demonstrates the principal properties of these techniques. We applied two different EEG source reconstruction techniques within different volume conductor models to localize induced spike activity in a selected patient suffering from medically intractable temporal lobe epilepsy: 1) single moving dipole solution in a 3-shell spherical model versus individual head models (boundary-element-model, BEM, and finite-element-model, FEM); 2) a regularization technique for current density reconstructions using both BEM and FEM. When compared to findings of invasive recordings no adequate source locations were derived from the moving dipole solution in both the 3-shell head model and BEM. In contrast, a high congruence of source reconstruction and invasive determination of the focus was obtained using the regularization techniques in both BEM and FEM, indicating the high spatial accuracy of this technique in individual head models.

Adult↗

Lowering the extracellular potassium concentration elicits epileptic activity in neocortical tissue of epileptic patients.

The increase in the extracellular potassium concentration ([K(+)](o)) is a well-established model of epilepsy (the so-called high potassium model). Therefore, it is generally accepted that for the prevention of abnormal excitability and seizure generation, increases of [K(+)](o) must be avoided. In this paper, however, we show that on the contrary, a reduction of [K(+)](o) also elicits epileptic activity in brain slices of man.

Adolescent↗