Assessment of cognitive functions before and after stereotactic interstitial radiosurgery of hypothalamic hamartomas in patients with gelastic seizures.

We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of (125)I-seed and 3 months after seed explantation. Performance was compared with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of (125)I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects.

[Suggestion for a new, patient-oriented epilepsy classification]. / Vorschlag für eine neue patientenorientierte Epilepsieklassifikation.

The recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes--at least as defined by the ILAE Task Force--group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

Laughter and the mesial and lateral premotor cortex.

We report the induction of laughter and smiling by cortical electrical stimulation of the frontal lobe of two patients: an 18-month-old boy with a left frontal cortical lesion extending to the vertex and the central gyrus, and a 35-year-old woman with a lesion in the right supplementary sensorimotor area (SSMA). The subjects underwent presurgical epilepsy evaluation with subdural grid electrodes to determine surgical candidacy. Stimulation of the prefrontal area reproducibly induced laughter. The adult patient reported absence of emotional content. Slowing of speech occurred under stimulation of electrodes in the upper and posterior vicinity. In this patient laughter was elicited in the anterior part of the SSMA. In the child, this response was induced by stimulation of the lateral prefrontal cortex near the midline. We conclude that the anterior portion of the SSMA/lateral premotor cortex is involved in generating the motor pattern of laughter.

Transient lesion in the splenium of the corpus callosum and antiepileptic drug withdrawal.

OBJECTIVE: To test pathophysiologic hypotheses regarding the occurrence of a splenial lesion in patients with epilepsy. METHODS: The authors studied 16 patients with a splenial lesion and 32 control patients, all of whom had MRI examination immediately after presurgical EEG long-term monitoring (LTM). The authors compared the number of generalized tonic-clonic and partial seizures during LTM, antiepileptic drug (AED) withdrawal, and laboratory results. RESULTS: All of the patients with a splenial lesion had their AEDs stopped completely, vs 47% of the controls (p = 0.001). Patients with SCC lesion had a longer duration of complete withdrawal (median 3.5 vs 2 days, p = 0.03). There was no correlation with seizure frequency or the introduction of new AEDs. CONCLUSION: A lesion of the splenium of the corpus callosum in patients with epilepsy is not associated with toxic drug effects or high seizure frequency, but might be induced by a rapid and relatively long-lasting reduction of antiepileptic drugs. Its frequency might be underestimated as MRI after long-term monitoring is rarely done.

Somatosensory auras in focal epilepsy: a clinical, video EEG and MRI study.

PURPOSE: To determine the clinical characteristics of somatosensory auras (SSA) and analyse features of seizure semiology predictive for localization in focal neocortical and limbic epilepsy. METHODS: This study analyses the clinical, video-EEG and MRI imaging features of 75 consecutive patients with focal epilepsy who described somatosensory auras at seizure onset to determine the frequency and localising value of SSAs in different types of focal epilepsy. Sensory characteristics, somatotopic distribution, evolution of the auras and subsequent ictal features in relation to MRI and EEG findings were analysed. RESULTS: The incidence of SSAs in 600 patients with focal epilepsy was 12%. Seventy-five patients were studied further: 77% reported tingling. Pain, thermal changes and a sense of movement or pulling were also reported. Distal unilateral auras in the hand and arm (46%) were most frequent and associated with a contralateral centroparietal focus. Contralateral auras were reported in 62% of lesional cases, focal cortical dysplasia was the commonest pathology in operated cases. Bilateral auras were associated with more diffuse pathologies or parasagittal foci. Evolution was centrifugal, somatotopic and usually unilaterally confined. Subsequent motor semiology was postural tonic, unilateral clonic, psychomotor or secondary generalized. CONCLUSION: SSA are highly correlated with centroparietal epilepsy but may occur in temporal lobe, mesial frontal and multifocal epilepsy. A lesional etiology including discrete dysplasias, tumours, ischemic and postencephalitic gliosis is likely.

Vagus nerve stimulation: predictors of seizure freedom.

OBJECTIVES: To identify predictive factors for the seizure-free outcome of vagus nerve stimulation (VNS). METHODS: All 47 patients who had undergone VNS implantation at one centre and had at least one year of follow up were studied. They underwent complete presurgical evaluation including detailed clinical history, magnetic resonance imaging, and long term video-EEG with ictal and interictal recordings. After implantation, adjustment of stimulation parameters and concomitant antiepileptic drugs were at the discretion of the treating physician. RESULTS: Mean (SD) age of the patients was 22.7 (11.6) years (range 7 to 53). Six patients (13%) became seizure-free after the VNS implantation. Only two variables showed a significant association with the seizure-free outcome: absence of bilateral interictal epileptiform discharges (IED) and presence of malformation of cortical development (MCD). Epilepsy duration showed a non-significant trend towards a negative association with outcome. By logistic regression analysis, only absence of bilateral IED correlated independently with successful VNS treatment (p<0.01, odds ratio = 29.2 (95% confidence interval, 2.4 to 353)). Bilateral IED (independent or bilateral synchronous) was found in one of six seizure-free patients and in 33 of 41 non-seizure-free patients. When bilateral IED were absent, the sensitivity for seizure-free outcome was 0.83 (0.44 to 0.97), and the specificity was 0.80 (0.66 to 0.90). CONCLUSIONS: Bilateral IED was independently associated with the outcome of VNS. These results are preliminary because they were based on a small patient population. They may facilitate prospective VNS studies enrolling larger numbers of patients to confirm the results.

Characterization of a fast transient outward current in neocortical neurons from epilepsy patients.

A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 +/- 1.8 mV (n = 5) and a slope factor of 17.0 +/- 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 +/- 8.3 mV (n = 5), with a slope factor of -6.6 +/- 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 +/- 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 microM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 microM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues.

MRI and EEG findings in surgically treated patients with partial seizures due to neuronal migration disorders, their relations to each other and to surgery outcome.

OBJECTIVES: To evaluate magnetic resonance imaging (MRI) and electro-encephalogram (EEG) findings of patients with therapy-resistant partial seizures due to neuronal migration disorders (NMD), and compare them with each other and with surgery outcome. MATERIAL AND METHODS: The MRI, interictal and ictal EEG findings, and their relations to each other in 41 patients with NMD were compared with class IA surgery outcome. RESULTS: The patients showed an MRI lesion in decreasing frequency from the frontal to the occipital areas. A predominantly extratemporal location of the interictal EEG foci (73.3%) and ictal patterns (82.4%) was therefore apparent, also showing a diminishing frequency from the anterior to the posterior areas. Comparing the EEG foci with the MRI lesions, the same location of the interictal foci was found in 68.4% and of the ictal foci in 52.7%, including several cases with a more widespread EEG focus or MRI lesion. The same location of interictal as well as ictal foci was evident in 85.7%. The most favourable surgery outcome (class IA) was, on average, apparent in patients with an MRI lesion (28.6% vs 25%), a main interictal EEG focus (50% vs 18%) and an ictal seizure pattern (37.5% vs 16.7%) located in the temporal area; likewise, if the interictal focus (30.8% vs 18.2%) and the ictal pattern (31.8% vs 12.5%) showed the same location as the MRI lesion, as well as when the interictal and ictal EEG changes had an equal location (30% vs 20%). CONCLUSION: MRI and EEG recordings show relatively close relations to each other and might be important methods to predict surgery outcome in NMD patients.

Stimulus-induced patterns of bioelectric activity in human neocortical tissue recorded by a voltage sensitive dye.

Stimulus-induced pattern of bioelectric activity in human neocortical tissue was investigated by use of the voltage sensitive dye RH795 and a fast optical recording system. During control conditions stimulation of layer I evoked activity predominantly in supragranular layers showing a spatial extent of up to 3000 microm along layer III. Stimulation in white matter evoked distinct activity in infragranular layers with a spatial extent of up to 3000 microm measured along layer V. The mean amplitude of optical signals close to the stimulated sites in layer I and white matter determined 25 ms following the stimulus, decreased by 50% at a lateral distance of approximately 900 microm and 1200 microm, respectively. Velocity of spread along the vertical stimulation axis reached 0.24 m/s in the supragranular layers (layers I to III) and then decreased to 0.09 m/s following layer I activation; stimulation of white matter induced a velocity of spread in layer V of 0.38 m/s, which slowed down to 0.12 m/s when passing the lower border of lamina IV. The horizontal velocities of spread determined from the stimulation site to a lateral distance of 500 microm reached 0.26-0.28 m/s and 0.28-0.35 m/s for layer I and white matter stimulation, respectively. At larger distances velocity of spread decreased. Increased excitability (Mg(2+)-free solution) had no significant effect on the spatio-temporal distribution of evoked activity as compared with control conditions. There were also no obvious differences between the results obtained in slices, which generated spontaneously sharp waves and those which were not spontaneously active. About 30% of the slices (n=7) displayed a greatly different response pattern, which seemed not to be related in a simple way to the stimulation as was the case in the majority of the investigated slices. The activity pattern of those slices appeared atypical in regard to their deviations of the vertical and horizontal extent of activity, to their reduced spatial extent of activity during increased excitability, to their layer-related distribution of activity, and to the appearance of afterdischarges.Concluding, in 30% of the human temporal lobe slices atypical activity pattern occurred which obviously reflect intrinsic epileptiform properties of the resected tissue. The majority of slices showed stereotyped activity pattern without evidence for increased excitability.

Language lateralization by Wada test and fMRI in 100 patients with epilepsy.

Comparing the determination of language dominance using fMRI with results of the Wada test in 100 patients with different localization-related epilepsies, the authors found 91% concordance between both tests. The overall rate of false categorization by fMRI was 9%, ranging from 3% in left-sided temporal lobe epilepsy (TLE) to 25% in left-sided extratemporal epilepsy. Language fMRI might reduce the necessity of the Wada test for language lateralization, especially in TLE.

Epilepsy surgery in children with focal cortical dysplasia (FCD): results of long-term seizure outcome.

The purpose of this study was to assess the effect of epilepsy surgery on seizure outcome in children and adolescents under 18 years with intractable epilepsy due to focal cortical dysplasia. We analysed clinical data, such as age at seizure onset, epilepsy course, localisation of focus from presurgical evaluation, MRI, tissue pathology and seizure outcome in 68 patients 6 months to 9 years after epilepsy surgery. Seizure outcome was classified according to the Engel classification. Mean age at seizure onset was 7 months, ranging from the first days of life to 7 years. All patients had medically intractable epilepsy. Localisation of the lesion was predominantly extratemporal: posterior (uni- or multilobar) 43 %, frontal without central region 26 %, multilobar involving central area 19 % and temporal in 12 %. MRI signs typically seen in cortical dysplasia (FCD) such as localised blurring of gray-white matter junction was found in 68 %, dysgyria in 62 %, thickening of the cortical ribbon in 46 % and T2 signal elongation of the subcortical white matter in 40 % of the patients' MRI. Age at surgery ranged from 5 months to 16 years; 14 patients were under 2 years when operated on. In 34 patients (6 patients under 3 years) subdural grid electrode evaluation was performed prior to surgery. Pathology revealed focal cortical dysplasia without balloon cells (type I) in 60 %, FCD of the balloon cell subtype (type II) in 40 % of the specimens. Postoperative complications were subdural hygroma in 5 and an increased motor deficit in 2 patients. Up to two years after epilepsy surgery 50 % of the children were seizure free (Engel class I), 10 % Engel class II, 33 % Engel class III and 7 % unchanged (Engel class IV). Long-term seizure outcome (> 3 years post surgery) in 32 patients showed similar results (class I 50 %, class II 19 %, class III 28 %, class IV 3 %). Complete resection of the dysplastic lesion was significantly correlated with favorable seizure outcome, whereas seizure outcome was not significantly different in patients with mild (type I) or balloon cell (type II) FCD. Children operated after 6 years of age had no better outcome than children operated in infancy or at preschool age. Epilepsy surgery resulted in good (class I and II) seizure control in 60 % of children with intractable epilepsy due to focal cortical dysplasia.

Epilepsy surgery outcome in children with focal epilepsy due to tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is frequently associated with focal epilepsy due to cerebral tubers. Seizures are the first symptoms in most patients with brain involvement. These epilepsies are frequently severe, drug-resistant and may have a negative impact on the child's global development. Although most epilepsies are multicentric, these patients may be candidates for epilepsy surgery, if it is possible to determine a leading epileptogenic tuber. Nine patients with TSC were examined with long-term video-EEG monitoring, different neuroimaging techniques and neuropsychological tests. A main epileptogenic tuber could be identified in all of our patients. We found good correlations between neuroimaging and EEG. Surgery was performed in eight patients. Seizure outcome was good in all. Two patients became seizure-free, one patient had a single prolonged seizure five days postoperatively, four patients had a significant seizure reduction of more than 75 % and one patient had a seizure reduction of more than 50 % after surgery without additional neurologic deficits. In conclusion, patients with TSC and drug-resistant epilepsy may benefit from epilepsy surgery with reduction in frequency and severity of seizures as well as improved mental and behavioural development leading to a better quality of life. In view of recent developments in functional and metabolic imaging, primary epileptogenic lesions will be more easily detectable in patients with diffuse brain involvement in TSC and surgical treatment may be more specifically applied at an earlier age to a selected subgroup of patients with this disorder.

Spreading depression in human neocortical slices.

Cortical spreading depression (CSD) occurrence has been suggested to be associated with seizures, migraine aura, head injury and brain ischemia-infarction. Only few studies identified CSD in human neocortical slices and no comprehensive study so far evaluated this phenomenon in human. Using the neocortical tissue excised for treatment of intractable epilepsy, we aimed to investigate CSD in human. CSD was induced by KCl injection and by modulating T-type Ca(2+) currents in incubated human neocortical tissues in an interphase mode. The DC-fluctuations were recorded by inserting microelectrodes into different cortical layers. Local injection of KCl triggered single CSD that propagated at 3.1+/-0.1 mm/min. Repetitive CSD also occurred spontaneously during long lasting application (5 h) of the T-type Ca(2+) channel blockers amiloride (50 microM) or NiCl(2) (10 microM) which was concomitant with a reversible extracellular potassium increase up to 50 mM. CSD could be blocked by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid in all cases. The results demonstrate that modulation of the Ca(2+) dynamics conditioned human neocortical slices and increased their susceptibility to generate CSD. Furthermore, these data indicate that glutamatergic pathway plays a role in CSD phenomenon in human.

Effects of retigabine on rhythmic synchronous activity of human neocortical slices.

The antiepileptic effects of the novel antiepileptic drug retigabine (D-23129) [N-(2-amino-4-(4-flurobenzylamino)phenyl) carbamid acid ethyl ester] were tested in neocortical slice preparations (n=23) from 17 patients (age, 3-42 years) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves, as well as of epileptiform field potentials (EFP) elicited by superfusion with Mg(2+)-free solution without or with addition of 10 micromol/l bicuculline. (1) Spontaneous rhythmic sharp waves (n=6), with retigabine application, the repetition rate was decreased down to 12-47% of initial value (10 micromol/l, n=3) after 180 min or suppressed completely within 12 min (50 micromol/l, n=3). (2) Low Mg(2+) EFP (n=9), with retigabine application, the repetition rate was decreased down to 50 and 65% of initial value (10 micromol/l; n=2) after 180 min or suppressed completely after 9-55 min (10, 50 and 100 micromol/l; n=2 in each case). In one slice only a transient reduction of the repetition rate was seen with 10 micromol/l retigabine. (3) Low Mg(2+) EFP with addition of bicuculline (n=8), with retigabine application, the repetition rate was decreased down to 12-55% of initial value (10 micromol/l; n=4) after 180 min or suppressed completely after 6-30 min (50 and 100 micromol/l; n=2 in each case). The depressive effect of retigabine was reversible in all but one slice. The results show a clear antiepileptic effect of retigabine in human neocortical slices on spontaneously occurring rhythmic sharp waves and different types of induced seizure activity.

Lack of aura experience correlates with bitemporal dysfunction in mesial temporal lobe epilepsy.

UNLABELLED: The diagnostic value of lack of aura experience in patients with temporal lobe epilepsy (TLE) is unclear. PURPOSE: To evaluate possible factors of bitemporal dysfunction in patients with mesial TLE who did not experience an aura in electroencephalography EEG/video monitoring for epilepsy surgery. METHODS: Ictal scalp EEG propagation patterns of 347 seizures of 58 patients with mesial temporal lobe sclerosis or non-lesional mesial TLE, interictal epileptiform discharges (IED), presence of unilateral mesial temporal lobe sclerosis in visual magnetic resonance imaging (MRI) analysis, prose memory performance, history or not of an aura, and postictal memory or absence of an aura were analyzed. The ictal EEG was categorized as follows. EEG seizure: (a) remaining regionalized, (b) non-lateralized, (c) showing later switch of lateralization or bitemporal asynchronous ictal patterns. RESULTS: Absent aura in monitoring was significantly correlated with absence of unitemporal MRI sclerosis (P=0.004), bitemporal IED (P=0.008), and propagation of the ictal EEG to the contralateral temporal lobe (P=0.001). Other historical data and interictal prose memory performance were not significantly correlated with absent aura. Ten of 11 patients without aura in monitoring also had absent or rare auras in their history. CONCLUSIONS: Lack of aura experience strongly correlates with indicators of bitemporal dysfunction such as bitemporal interictal sharp waves and bitemporal ictal propagation in scalp EEG, and absence of lateralized MRI sclerosis in patients with mesial TLE. The fact that absent auras are not correlated with episodic memory suggests a transient memory deficit, probably because of rapid propagation to the contralateral mesial temporal lobe.

A detailed analysis of frontal lobe seizure semiology in children younger than 7 years.

PURPOSE: We sought to analyze semiology of seizure onset and evolution in young children with frontal lobe epilepsy (FLE), compare this with adult reports, and assess age-related differences. METHODS: We analyzed 111 videotaped seizures from 14 patients with FLE based on focal cortical dysplasia aged 3-81 months (mean, 30 months). Ictal events were categorized into behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included tonic, clonic, epileptic spasm, and myoclonic seizure components. We developed a time-scaled datasheet to record each epileptic event as onset, very early, early, or late manifestation. RESULTS: Patients had a high seizure frequency with up to 40 attacks/day; half of them showed a cluster tendency. Forty-seven percent of the seizures started in sleep. Mean duration of seizures was short (29 s). Most common seizure components were motor manifestations, mostly tonic-clonic seizures, and epileptic spasms. Behavioral change was frequent, and hypermotor seizures were not seen. In five patients, the motor features were contralateral to the epileptic focus, including two children with asymmetric epileptic spasms. Secondarily generalized tonic-clonic seizures (SGTCSs) were not recorded, but had been reported in the history of two patients. Complex motor automatisms were not seen, whereas oral automatism appeared in three children. CONCLUSIONS: Motor features are common in young children with FLE, as reported in adults. The characteristics, however, differ. Epileptic spasms and subtle behavioral change were frequent. Hypermotor seizures and complex motor automatisms were not seen, and SGTCSs were unusual. Our results suggest that FLE in young children shows age-related features differing from those of adults.

Effects of nifedipine on rhythmic synchronous activity of human neocortical slices.

The antiepileptic effect of the dihydropyridine calcium channel blocker nifedipine was tested in neocortical slice preparations (n=27) from patients ranging in age from four to 46 years (mean=25) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves as well as of untriggered epileptiform field potentials induced by omission of Mg(2+) from the superfusate, or epileptiform field potentials elicited by application of bicuculline and triggered by single electrical stimuli. (1) Spontaneous rhythmic sharp waves (n=6): with nifedipine (40micromol/l), the repetition rate was decreased down to 30% of initial value, whereas the area under the field potential remained nearly unchanged. (2) Untriggered low Mg(2+) epileptiform field potentials (n=6): with nifedipine (40micromol/l) the area under the field potentials was reduced while the action on the repetition rate was ambiguous. (3) Triggered bicuculline epileptiform field potentials (n=15): with nifedipine (40micromol/l; n=4), no antiepileptic effect was found. There was, however, a marked increase in the area under the epileptiform field potentials. The area under the field potentials was reduced only at a dosage of 60micromol/l (n=11). This effect was stronger when nifedipine was applied with a K(+) concentration raised from 4 to 8mmol/l. The results show that the calcium channel blocker nifedipine is able to reduce differential epileptiform discharges in human neocortical tissue. These observations are in line with previous findings, suggesting that calcium flux into neurons is involved in epileptogenesis. The present results therefore support the idea that some organic calcium antagonists may be useful in human epilepsy therapy, although the etiology of epileptic seizures seems to be a critical factor for the efficacy of the drug.