Search

Purpose: Refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality. We aimed to analyze the long-term outcome of intensive care unit (ICU)-treated RSE and super-refractory status epilepticus (SRSE) patients in a population based cohort., Methods: A retrospective study of ICU- and anesthesia-treated RSE patients in Kuopio University Hospital's (KUH) special responsibility area hospitals in the central and eastern part of Finland from Jan. 1, 2010 to Dec. 31, 2012 was conducted. KUH's catchment area consists of five hospitals-one university hospital and four central hospitals-and covers a population of 840 000. We included all consecutive adult (16 years or older) RSE patients admitted in the participating ICUs during the 3-year period and excluded patients with postanoxic etiologies. We used a modified Rankin Scale (mRS) as a long-term (1-year) outcome measure: good (mRS 0-3, recovered to baseline function) or poor (mRS 4-6, major functional deficit or death)., Key Findings: We identified 75 patients with ICU- and anesthesia-treated RSE, corresponding to an annual incidence of 3.0 (95% confidence interval (CI) 2.4-3.8). 21% of the patients were classified as SRSE, with the annual incidence being 0.6/100 000 (95% CI 0.4-1.0). For RSE, the ICU mortality was 0%, hospital mortality was 7% (95% CI 1.2%-12.8%) (n=5), and one-year mortality was 23% (CI 95% 13.4%-32.5%) (n=17). 48% (n=36) of RSE patients recovered to baseline, and 29% (n=22) showed neurological deficit at 1year. Poor outcome (mRS 4-6) was recorded for 52% (n=39) of the patients. Older age was associated with poorer outcome at 1year (p=0.03). For SRSE, hospital mortality was 6% (n=1) and 1-year mortality was 19% (n=3) (95%CI 0%-38.2%)., Significance: During 1-year follow-up, nearly 50% of the ICU-treated RSE patients recovered to baseline function, whereas 30% showed new functional defects and 20% died. SRSE does not have a necessarily poorer outcome. The outcome is worse in older patients and in patients with progressive or fatal etiologies. SE should be treated with generalized anesthesia only in refractory cases after failure of adequately used first- and second-line antiepileptic drugs., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: A study was carried out to assess the outcome of initial antiepileptic drug (AED) monotherapy in elderly patients with newly diagnosed epilepsy and to investigate the cumulative probabilities of ≥2- and ≥5-year complete seizure remission and the factors that may have an effect on the outcome of AED treatment and the response to successive AED regimens., Methods: From the medical records of Kuopio University Hospital, Finland, the researchers identified a community-dwelling cohort of elderly subjects (aged 65 or above at the time of diagnosis; n=529) with newly diagnosed epilepsy. The seizure outcome and the effect of initial prescription of AEDs were retrospectively studied., Results: All told, 336 (64%) of the patients used the initial AED for the whole follow-up period, while the treatment was changed for 193 (36%) of the patients. In total, 456 (86%) of the 529 patients were treated with monotherapy until the end of follow-up. Four per cent of the patients developed refractory epilepsy. The response to the second monotherapy after failure of the first monotherapy was similar between patients whose treatment failed for reason of intolerable side effects and those showing failure due to inadequate seizure control. The estimated cumulative probability of achieving ≥2 years' remission was 83%, and that for achieving ≥5 years of remission was 79%. Early response to treatment was a statistically significant predictor of remission., Conclusion: The prognosis of seizures in elderly patients with newly diagnosed epilepsy is good, and most patients can be successfully treated with the first AED. Patients who do not become seizure-free within the first year may be at risk of displaying a drug-resistant seizure disorder., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Unverricht-Lundborg disease (EPM1) is characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic seizures and ataxia. Several disease-related alterations in cortical structure and excitability have been associated with the motor symptoms of EPM1. This study aimed to elucidate possible alterations in cortical activation related to motor performance in EPM1., Methods: Fifteen EPM1-patients and 15 healthy volunteers matched for age and sex underwent motor functional MRI. Group differences in activations were evaluated in the primary and supplementary motor cortices and sensory cortical areas. Furthermore, in EPM1 patients, the quantitative fMRI parameters were correlated with the severity of the motor symptoms., Results: The EPM1-patients exhibited decreased activation in the left inferior frontal junction (IFJ) during right hand voluntary motor task when compared with controls. In the quantitative analysis, EPM1-patients had significantly weaker activation than controls in the hand knob and supplementary motor areas (SMA). The volume of activation in M1 decreased with age and duration of disease in the patient group, whereas the volume increased with age in controls. Negative correlations were observed between fMRI parameters of SMA and disease duration or age in patients but not in controls., Conclusions: The weaker motor fMRI activation observed in EPM1 patients parallels previous neurophysiological findings and correlates with the motor symptoms of the disease. Thus, the observed decrease in IFJ activation in EPM1 patients may be associated with the difficulties in initiation or termination of motor execution, a typical clinical symptom in EPM1. The fMRI findings reflect the progressive nature of this disease., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Long-term cognitive and memory performance after surgical treatment of unilateral temporal lobe epilepsy (TLE) was investigated in a series of 98 patients. Neuropsychological evaluation was performed preoperatively and after one and three years postoperatively. Fifty-eight patients (59%) became seizure-free (Engel's class I). Verbal learning and memory declined in long-term follow-up in both left and right TLE groups. Visual memory remained stable. Ongoing postoperative seizures were related to decline in the immediate recall of logical prose, and postoperative seizure-freedom to improvement in verbal fluency in patients with left TLE. There was significant variability in the individual postoperative long-term memory performance. Left side of surgery, better baseline performance and older age at surgery were identified as risk factors for individual decline in delayed verbal memory. Selected patients undergoing surgery for drug-resistant TLE are at risk for significant postoperative memory decline especially after left temporal lobe surgery. Preoperative counseling and long-term follow-up of cognitive performance in individual patients is recommended. Additionally, more accurate predictors of individual postoperative memory performance would be needed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Unverricht-Lundborg disease (EPM1) is an inherited neurodegenerative disorder, and the most common form of progressive myoclonus epilepsies. Its main symptoms, epileptic seizures and drug-resistant myoclonus, may be associated with neurophysiological evidence of abnormal cortical excitability or reduced inhibition. The aim of the present study was to utilize transcranial magnetic stimulation (TMS) to induce cortical responses measured with electroencephalography (EEG) in order to observe prevailing cortical excitability/inhibition changes, as well as power and coherence of the cortical oscillations in EPM1. We studied 7 genetically verified EPM1 patients (4 female; age 36±6 years) and 6 healthy control subjects (1 female; age 34±12 years). Navigated TMS was focused on the left primary motor cortex at the representation area of the right thumb. TMS-EEG responses were measured at 90% of the resting motor threshold intensity in 110-150 trials. We observed that P30 waveform following the TMS was significantly (p<0.05) increased in EPM1 patients suggesting increased cortico-cortical excitability, while the later N100/P180 waveform was significantly (p<0.05) decreased indicating reduced inhibition. In the event-related spectral perturbation (ERSP), we found that alpha, beta and gamma band oscillations following the TMS were significantly lower in power in the EPM1 patients compared to controls. In the alpha and beta bands, the inter-trial coherence (ITC) representing the degree of synchronization was also decreased in EPM1. Our results suggest abnormal reactivity in EPM1, and may indicate impaired cortico-cortical inhibition and attenuation of subsequent cortical circuits or the thalamic or subcortical nuclei., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive method to localize the primary motor cortex (M1)., Objective/hypothesis: To assess the safety and feasibility of nTMS as a non-invasive preoperative mode of functional localization of M1 in epilepsy surgery candidates with intractable focal epilepsy due to lesions in the vicinity of M1., Methods: We mapped the muscle representation areas of M1 with nTMS in 10 patients (age 2 to 55 years) with intractable epilepsy. The lesions were focal cortical dysplasia (n=6), ganglioglioma (n=2) polymicrogyria (n=1) or dysembryoblastic neuroepithelial tumour (n=1). The optimal stimulation sites and motor threshold (MT) of the distal hand or leg muscles were determined in both hemispheres. Cortical areas were mapped with stimulation intensities 100-120% of the MT to localize functional M1. Patients were on their stabile antiepileptic medication, and EEG was continuously monitored. The clinical benefit obtained with the preoperative nTMS mapping in the surgical decision making was scored as (1) essential, (2) beneficial, or (3) not beneficial, depending mainly on the difference between the functional and the presumed anatomic M1., Results: The M1 was successfully assessed in all but the 2 youngest patients (aged 2 and 5 years), in whom nTMS was unable to elicit motor responses. nTMS was regarded as essential or beneficial in the localization of M1 in relation to the lesions in 6 out of 10 cases. The optimal motor representation areas were mainly located symmetrically on the precentral gyrus, and corresponded to the presumed location of M1 in MRI. No clinical or EEG evidence of acute epileptogenic adverse effects were observed during the localization procedure. None of the operated patients developed post-operative motor deficits., Conclusions: nTMS is a safe and feasible clinical tool for the non-invasive preoperative localization of motor cortex in patients with intractable epilepsy due to focal lesions adjacent or within the presumed M1 in MRI., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: A gabaergic antiepileptic drug, vigabatrin (VGB), is known to induce bilateral concentric visual field defects (VFD) in 30-40% of treated patients. Although the clinical and electrophysiological features of VFDs are well documented, the mechanism of retinal toxicity is still unclear., Purpose: To determine if low basal ornithine-δ-aminotranspherase (OAT) activity is implicated in the etiology of VGB retinotoxicity, resulting in a phenotype of a mild form of gyrate atrophy., Methods: Assays of OAT activity in lymphocytes and GABA-transaminase activity in platelets were performed, and plasma levels of GABA, ornithine, lysine, glutamic acid and glutamine were measured, and visual fields were examined. A total of 47 subjects, aged 14-78 years, were examined. Twenty-one epileptic patients were off VGB more than 1 year; 11 patients with VGB-induced VFD and 10 with normal visual fields. Ten epileptic patients were on current VGB therapy more than 1 year; four patients with VGB-induced VFD and six with normal visual fields. The results were compared with those of 10 epilepsy patients taking tiagabine and six patients who suffered from gyrate atrophy (GA) or were obligate carriers of the disease., Results: In patients who had stopped VGB and who had VFDs, OAT activity was significantly reduced as compared with those who had normal visual fields (77.4pmol P5C/min/mgPro vs. 181.9pmol P5C/min/mgPro, p=0.002). In patients with ongoing VGB therapy, no difference was found between the patients with and without VFDs (149.4pmol P5C/min/mgPro vs. 159.1pmol P5C/min/mgPro)., Conclusions: : The results suggest that VGB retinotoxicity might be associated with elevated retinal ornithine mediated by low basal OAT activity., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Purpose: Progressive myoclonus epilepsies (PMEs) comprise a heterogeneous group of conditions characterized by an imbalance between excitatory and inhibitory neuronal mechanisms. The aim of this study was to assess the function of the motor cortex in Unverricht-Lundborg disease (ULD), progressive myoclonus epilepsy type 1 (EPM1)., Methods: Genetically verified EPM1 patients (n=24) were studied and compared with healthy subjects (n=24). MRI-navigated transcranial magnetic stimulation (TMS) was used to study the function of the motor cortex. Motor threshold (MT) and cortical silent period (SP) were used as parameters to evaluate cortical excitability. Peripheral muscle responses were recorded at the thenar and hypothenar using on-line electromyography (EMG)., Results: The normal shortening of SP duration with age was not evident in EPM1. Thus, older patients exhibited significantly prolonged SPs in comparison to healthy control subjects (p<0.05). The MTs, measured as both stimulator output percentage and induced electric field strength (EF), were significantly higher in EPM1 patients than in control subjects (p<0.001). The stimulation of the thenar caused a co-activation in the hypothenar with significantly higher amplitudes as compared to controls (p<0.05)., Conclusions: The prolongation of the SPs with age in EPM1 patients suggests a prevailing inhibitory tonus of the primary motor cortex (M1) as possible reactive mechanism to the disease. Antiepileptic drugs may contribute to the increased MT but do not affect the SP. The results and methodology of this study can lead to a better understanding of the pathophysiology and progression of EPM1.

Purpose: Ring chromosome 20 [r(20)] syndrome is a rare chromosomal disorder. Cases tend to be sporadic. We elucidate the characteristics of an inherited r(20) mosaicism by describing the clinical features of three family members: a mother and her two children., Results: The mosaicism rate of the mother was 10% and that of the children 40%. The mother experienced her first epileptic seizures at 24 years of age. Epilepsy was diagnosed two years later. After an unstable period lasting 3 years, she has been seizure-free for 13 years on a combination of valproate and lamotrigine. She has normal intelligence with full working capacity. The daughter exhibited her first epileptic seizures at the age of 7 years and she continues to have seizures weekly. The first epileptic seizures in the son were observed at 5 years of age. The son's epilepsy has been drug resistant from the onset, and a vagal nerve stimulator (VNS) has been ineffective. Psychomotor development was normal in both children up to the onset of epilepsy. Learning difficulties increased throughout school age and both children needed special educational programs. Neuropsychological evaluations have shown deterioration of cognitive levels. Both children had behavioural problems during school age but no longer in adolescence. All three subjects are nondysmophic, normocephalic and of normal growth., Conclusion: In this family the phenotype of r(20) mosaicism seems to be more severe in the successive generation along with a greater level of mosaicism. The aggravated clinical picture in inherited r(20) mosaicism concerned the onset of epilepsy, drug responsiveness, the cognitive level and behavioural features.

Purpose: To examine possible changes over time in the incidence of epilepsy in different age groups., Methods: Based on the nationwide full-refundable antiepileptic drug register and population register, incidence of newly diagnosed epilepsy was measured by granted full-refundable antiepileptic drugs for epilepsy., Results: The incidence was throughout all age groups higher in men than in women. The incidence in the total population had significantly declined in 1986-2002, from 71.6/100,000 to 52.9/100,000. The incidence significantly decreased in children (0.77; 0.71-0.84, p<0.0001) and adults (0.83; 0.77-0.89, p<0.0001) but increased in the elderly (1.18; 1.10-1.26, p<0.0001). The increased incidence in the elderly over the time period was primarily seen in women., Conclusion: The incidence of epilepsy has significantly declined in both children and adults with a concurrent increase in the incidence among the elderly. Further studies are needed to elucidate the precise cause of these temporal changes.

The purpose of the study was to determine whether the use of a GABAergic antiepileptic drug (AED), tiagabine, affects color vision and contrast sensitivity. Twenty newly diagnosed patients with partial epilepsy (aged 19-72 years), receiving tiagabine as their initial monotherapy for 5-41 months were examined. Color vision was examined with the Standard Pseudoisochromatic Plates 2 (SPP2), with the Farnsworth-Munsell 100 Hue Test (FM100) and with the Color Vision Meter 712 (CVM) anomaloscope. Contrast sensitivity was measured with the Pelli-Robson letter chart. Three patients excluded from the color vision evaluation for congenital red-green color vision defects. Seven out of 17 patients (41%) had acquired color vision deficit examined with the FM100. The CVM anomaloscope revealed minor defects in two patients. Contrast sensitivity function was within normal ranges. The present study suggests that AED therapy with tiagabine, like with other established and newer AEDs may interfere with color perception.

Purpose: To evaluate neurological and cognitive functioning of school-aged (> or =6 years) children exposed to valproate monotherapy in utero in a population based, evaluator-blinded, controlled study., Methods: Studied children (N=39, aged 6.6-13.4 years) and their mothers were identified through a population based pregnancy registry. Mothers with carbamazepine monotherapy and mothers with epilepsy but without antiepileptic drug (AED) treatment during pregnancy and their age and gender matched children served as controls. Hospital records were reviewed and neurological examination (Touwens test), intelligent quotients (IQ) of mothers (WAIS), and children (WISC-III) and neuropsychological assessment of children (NEPSY) were performed evaluator-blinded., Results: The prevalence of low intelligence (FIQ<80) was 19% (4/21) and the prevalence of exceptionally low intelligence (FIQ<70) 10% (2/21) in valproate (VPA) monotherapy exposed children. Children exposed to carbamazepine (CBZ) and children of women with epilepsy but without AED exposure during pregnancy had all at least low average intelligence. The mothers using valproate scored significantly lower (p<0.05) in FIQ, VIQ and PIQ tests and had also significantly lower (p=0.035) educational level. Altogether 21% (8/39) of the children had minor neurological dysfunctions., Conclusions: In a population based setting inheritance and cumulating environmental factors may partly explain the increased prevalence of neurocognitive symptoms in children exposed to valproate in utero although concern about the possible long-term effects of intrauterine valproate exposure does exist.

Vigabatrin (VGB) is an important treatment option for infantile spasms. Vigabatrin-induced visual field defects are at present the most important safety issue in the use of the drug. The knowledge concerning VGB-associated visual dysfunction in pediatric patients, particularly in those who have been exposed to VGB in utero is limited. We explored ophthalmic and neurologic findings in two children who have been exposed prenatally to VGB.

Patients with drug-refractory temporal lobe epilepsy (TLE) often have hippocampal and amygdaloid damage. The present study investigated the factors associated with the occurrence and severity of damage in patients with partial epilepsy. Magnetic resonance imaging was used to measure the volumes of the hippocampus and the amygdala in 241 patients with different durations of epilepsy. We also investigated the association of damage with the location of seizure focus and clinical factors (age at onset of seizures, lifetime seizure number and medical history of complex febrile convulsions, intracranial infection or status epilepticus) with regression analysis. We found that high lifetime seizure number (P<0.05), history of complex febrile convulsions (P<0.01), and age < or = 5 years at the time of the first seizure (P<0.01) were significant risk factors for reduced hippocampal volume in TLE patients. The severity of amygdaloid damage did not differ between TLE patients with different durations of epilepsy or seizure frequency, but complex febrile convulsions (P<0.05) and intracranial infection (P<0.05) were associated with amygdaloid damage. In patients with extratemporal or unclassified partial epilepsy, the hippocampal and amygdaloid volumes did not differ when patients with different durations of epilepsy were compared with controls. The present findings indicate that a high seizure number, the occurrence of complex febrile convulsions, and an early onset of seizures contribute to hippocampal volume reduction in patients with TLE. The data provided have important implications with regard to early and effective management and seizure control in vulnerable patients.

It is difficult to design valid and well-controlled monotherapy trials that satisfy regulatory requirements and, at the same time, demonstrate the usefulness of a new drug in clinical practice. The conversion design is a drug-substitution trial in which patients with uncontrolled seizures are assigned to add-on treatment with an investigational drug and, usually, an appropriate control, after which pre-existing treatment is gradually discontinued. In the most utilised design, patients are randomised to receive a high dose versus low dose of the new drug, while concomitant medication is gradually discontinued. Exit criteria are predetermined to prevent excessive deterioration of seizures, and treatment retention time is used as the primary outcome variable to measure the effectiveness of the allocated treatments: the goal is to demonstrate higher retention rates in the high-dosage group. Conversion studies may help to fill some gaps in knowledge regarding efficacy and tolerability as monotherapy before larger-scale de-novo studies are started. In the de-novo design, newly diagnosed patients are randomised to receive the investigational drug or an active control. In equivalence (or non-inferiority) trials, the active control is usually an established antiepileptic drug (AED) such as carbamazepine or valproate, and outcome parameters may include proportion of patients achieving a predefined (for example, 6-month) seizure remission or the proportion of patients remaining in the trial (retention rate, a combined measure of efficacy and tolerability). In regulatory trials designed to show a difference, newly diagnosed patients are randomised to a high versus a low dose of the investigational drug, and exit criteria are again predetermined for patients whose seizures are not adequately controlled. In this case, outcome parameters may include time to first seizure in addition to retention in the trial. Comparative monotherapy trials in newly diagnosed patients are relevant to approximately 50% of the patients who develop epilepsy and can be satisfactorily managed with a single drug. These trials allow direct head-to-head comparisons and avoid the confounding effects of baseline drugs and co-medication withdrawal present in conversion studies. Long-term follow-up of patients who are receiving a drug in monotherapy at adequate doses gives the most clinically relevant answers regarding the usefulness of a new drug. It is concluded that the de-novo design is the gold standard when studying AEDs as monotherapy, but the conversion-to-monotherapy design can be used before starting the de-novo program in order to obtain estimates of efficacy and tolerability of the AED as monotherapy in a population of difficult-to-treat patients. With both designs, the use of suboptimal comparators incorporated into some of the regulatory trials is a cause of ethical concern.

Tiagabine is currently recommended mainly as add-on therapy in adults and children above 12 years with partial epilepsy not satisfactorily controlled with other antiepileptic drugs. Based on available evidence and our clinical experience, tiagabine should be used preferably in patients sharing one or more of the following additional features, (i) a history of drug-induced cutaneous adverse events; (ii) mild to moderate epilepsy allowing for a slow titration and gradual onset of anticonvulsant action over a few weeks; (iii) patients for whom it is particularly important to avoid a deterioration in cognitive performance; and, (iv) patients who failed to respond to previous treatment with sodium channel blocker agents as they may particularly benefit from the introduction of tiagabine, due to its GABAergic mechanism of action. Tiagabine can also be used successfully in other patients with refractory partial epilepsy. Tiagabine is not indicated for patients with generalized or unclassified epilepsies and for patients with severely impaired liver function.

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic-clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.

The epilepsy patients whose seizures will prove to be refractory should be identified as early as possible, and thus the need for new prognostic factors of intractable epilepsy is evident. The aim of the study was to investigate predictors of seizure outcome in a multivariate analysis. Neurological, electroencephalography (EEG) and neuropsychological variables were analyzed as potential predictors of epilepsy. Eighty-nine newly diagnosed adult patients with partial epilepsy were, after a prospective 2-year follow-up period, categorized into one of the two groups: patients with satisfactorily controlled epilepsy, and patients with refractory epilepsy. Six variables predicted 2-year seizure outcome: presence of spike focus in EEG, partial complex or mixed seizure type, remote symptomatic etiology, moderately impaired memory performance in immediate recall and in delayed recognition of the word list, and age at the time of diagnosis. The correct seizure outcome could be predicted with the model in 94% of newly diagnosed epilepsy patients. The presence of verbal memory impairment at the time of the diagnosis of partial epilepsy is a significant predictor of seizure outcome and, together with clinical and EEG variables, it predicts seizure outcome in the majority of the patients. Memory performance as a prognostic factor is of most value in patients with risk of refractory epilepsy and when used in a multidisciplinary setting.

The amygdala complex is one component of the temporal lobe that may be damaged unilaterally or bilaterally in children and adults with temporal lobe epilepsy (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging studies of epileptic patients have shown that volume reduction of the amygdala ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been reported in the lateral and basal nuclei. Studies in rats have more specifically identified the amygdaloid regions that are sensitive to status epilepticus-induced neuronal damage. These areas include the medial division of the lateral nucleus, the parvicellular division of the basal nucleus, the accessory basal nucleus, the posterior cortical nucleus, and portions of the anterior cortical and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular and intermediate divisions of the basal nucleus and the central nucleus, remain relatively well preserved. Amygdala kindling studies in rats have shown that the density of a subpopulation of GABAergic inhibitory neurons that also contain somatostatin may be reduced even after a low number of generalized seizures. While analyses of histological sections and MR images indicate that in approximately 10% of TLE patients, seizure-induced damage is isolated to the amygdala, more often amygdala damage is combined with damage to the hippocampus and/or other brain areas. Moreover, recent data from rodents and nonhuman primates suggest that structural and functional alterations caused by seizure activity originating in the amygdala are not limited to the amygdala itself, but may also affect other temporal lobe structures. The information gathered so far on damage to the amygdala in epilepsy or after status epilepticus suggests that local alterations in inhibitory circuitries may contribute to a lowered seizure threshold and greater excitability within the amygdala. Furthermore, damage to select nuclei in the amygdala may predict impairment of performance in behavioral tasks that depend on the integrity of the amygdaloid circuits.

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.

Little is known about the appearance and severity of amygdaloid damage in temporal lobe epilepsy, particularly in its early stages. In the present magnetic resonance imaging study, we measured amygdaloid volumes and T2 relaxation times in 29 patients with newly diagnosed and in 54 patients with chronic temporal lobe epilepsy. The control population included 25 normal subjects. In the newly diagnosed patients, the mean amygdaloid volume did not differ from that in controls. Also, in the chronic patients the mean amygdaloid volume did not differ from that in controls or in newly diagnosed patients. However, in 19% of the chronic patients the amygdaloid volume was reduced by at least 20%. Moreover, in all of the epilepsy patients, both chronic and newly diagnosed, we found an inverse correlation between the number of epileptic seizures the patient had experienced and the amygdaloid volume on the focal side (focus on the left, r = -0.371, P < 0.01; focus on the right, r = -0.348, P < 0.05). The mean T2 relaxation time in newly diagnosed or chronic patients did not differ from each other or from control values. However, the T2 relaxation time of the left amygdala was > or = 111 msec (i.e., > or = 2 S.D. over the mean T2 time of the left amygdala in control subjects) in seven (10%) patients, one of which was newly diagnosed and six were chronic. The T2 time of the right amygdala was prolonged in eight (12%) patients, three of which were newly diagnosed and five were chronic. We did not find any clear asymmetries in amygdaloid volumes or T2 relaxation times between the ipsilateral and contralateral sides relative to seizure focus. According to the present findings, signs of amygdaloid damage were observed in approximately 20% of patients with temporal lobe epilepsy, most of which had chronic epilepsy.

A new anti-epileptic drug, tiagabine, is a potent inhibitor of GABA uptake into neurons and glia. Tiagabine has shown promising efficacy and safety profiles as add-on treatment for partial seizures. We evaluated the long-term effects of tiagabine on cognition and EEG in 37 patients with partial epilepsy. The study protocol consisted of a randomized, double-blind, placebo-controlled, parallel-group add-on study and an open-label extension study. During the 3 month double-blind phase at low doses (30 mg/day) tiagabine treatment did not cause any cognitive or EEG changes as compared with placebo. Tiagabine treatment did not cause deterioration in cognitive performance or produce any rhythmic slow-wave activity or other constant, new abnormalities on EEG during longer follow-up with successful treatment on higher doses after 6-12 months (mean 65.7 mg/day, range 30-80 mg/day) and after 18-24 months (mean dose 67.6 mg/day, range 24-80 mg/day). The daily dosages in the long-term follow-up of the present study are higher than in the previous reports.

Verbal learning and memory of 56 adults with newly diagnosed partial epilepsy and no other known brain pathology were compared with memory performance of a normal control group. Memory was evaluated with a list learning test and with recall of logical prose under both immediate and delayed recall conditions. The patients and the controls did not differ in immediate and delayed recall of logical prose. Also learning and immediate recall of the word list was comparable in both groups. After delay the patients recalled fewer words than the control group (P < 0.001), and the percent retention of words was lower in the patients (P < 0.001). The patients with newly diagnosed epilepsy more frequently exhibited mild verbal memory dysfunction as shown in delayed recall of word list. Moderate memory impairment is seen in a group of patients who have deficits in immediate and delayed memory. Follow-up is needed to find out whether patients with memory deficits at the time of diagnosis are those who develop intractable chronic epilepsy.

We evaluated the effect of initial oxcarbazepine (OXC) monotherapy on memory, attention and simple psychomotor speed in 14 patients; 15 patients with initial phenytoin (PHT) monotherapy served as reference patients. Neuropsychological assessments were performed before starting the treatment and after 6 and 12 months follow-up with steady-state drug treatment. Differential cognitive effects of OXC and PHT were not apparent in our study. As the efficacy of present antiepileptic drugs in adult epilepsy is analogous, the choice of drug is determined by the comparative side effects of the drugs. In the present study the number of successfully treated patients was similar in both OXC and PHT groups. As far as cognitive side effects are concerned our results revealed no evidence favoring either antiepileptic over the other.

Baltic myoclonus epilepsy (BME) is a neurodegenerative disease characterized by tonic-clonic seizures, myoclonus and a progressive course. The aim of the present study was to assess the clinical symptoms and signs of possible involvement of the autonomic nervous system (ANS) and objectively evaluate autonomically mediated cardiovascular reflexes in this syndrome. Fifteen patients with BME and 14 healthy control subjects were studied. Thirteen (87%) of the patients had symptoms suggesting ANS dysfunction. The most common symptoms were postural dizziness and sweating disturbances. The heart rate variation during deep breathing was lower in patients than in controls. The heart rate response and systolic blood pressure response during tilting were similar in both groups. Our results suggest a mild parasympathetic hypofunction and an intact sympathetic function in ambulatory patients with BME.

Incidence of CT abnormalities and their correlation with clinical and EEG features were evaluated in a consecutive series of 202 adult patients with newly diagnosed epileptic seizures. Abnormal CT findings were found in 36% of these patients; the abnormalities consisted of brain tumors (17%), atrophic lesions (11%) and other organic findings (8%) such as arteriovenous malformations. Focal features of seizures, in neurological examination and/or in EEG, correlated significantly with CT abnormalities. The absence of these findings did, however, not exclude the possibility of brain lesions, which in many cases were treatable by surgery.