Christoph Kurth

Seizure anticipation by patients with focal and generalized epilepsy: A multicentre assessment of premonitory symptoms

PURPOSE To assess subjective seizure anticipation in patients with focal and generalized epilepsy. METHODS Five hundred consecutively recruited out-patients (251 male, 249 female, mean age 38.1 year) from three German tertiary epilepsy referral centres filled out questionnaires regarding subjective anticipation of seizures by at least 30 min and to timing and semiologic characteristics of their premonitory symptoms versus those of ictal phenomena. Patients were not regarded as having prodromi if the semiology of symptoms reported long before a seizure was identical to auras. RESULTS 6.2% of patients reported that they were able to anticipate seizures. Premonitory symptoms were classified as stereotyped in all but one patient. An intraindividual semiologic analysis showed that the majority of these patients had symptoms, which were distinct from ictal experiences during auras. Seizure anticipation was reported both by patients with focal and idiopathic generalized epilepsy. The median estimated time interval between occurrence of premonitory symptoms and seizure onset was 90 min. CONCLUSIONS This study gives evidence that both patients with focal and idiopathic generalized epilepsy may subjectively anticipate the occurrence of epileptic seizures. Premonitory symptoms are distinct from auras in terms of semiology and time of occurrence. The lower percentage of patients regarded as having premonitory symptoms as compared to some earlier reports may be related to stricter criteria and to the exclusion of auras, which could directly evolve into seizures, and other ictal events. Premonitory symptoms occur at similar periods prior to seizures as anticipatory EEG-changes have been reported using methods from time series analysis.

Oxidative stress and an altered methionine metabolism in alcoholism.

The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (P<0. 01) between blood alcohol concentration and elevated homocysteine (Spearmans r=0.71) and malondialdehyde (r=0.90) levels on admission. In addition, homocysteine and malondialdehyde levels were found to be significant decreased after 3 days of withdrawal treatment (Wilcoxon test: homocysteine, Z=-5.127; malondialdehyde, Z=-3.120; P<0.01). We postulate that excitatory neurotransmitters and mechanisms of oxidative stress in patients with chronic alcoholism may partly mediate excitotoxic neuronal damage and hereby cause brain shrinkage.

Ictal near infrared spectroscopy in temporal lobe epilepsy: a pilot study

Near infrared spectroscopy (NIRS) is a non-invasive method to measure cerebral tissue oxygenation continuously with an adhesive optode system which can be easily placed on the skin. We coupled NIRS with video-electroencephalography (video-EEG) during the presurgical evaluation of two patients with intractable localization-related epilepsy of mesial temporal origin. Cerebral oxygen saturation was measured either ipsilaterally (three seizures) or contralaterally (four seizures) to the primary epileptogenic zone. Since NIRS measures cerebral tissue oxygenation in a depth of only few centimetres, it did not record within the primary epileptogenic zone in our patients. Therefore we decided to place the NIRS optodes comfortably for the patients on the hairless skin corresponding with measurement of the oxygenation within the corresponding frontal cortex. Ipsilateral measurement revealed a marked desaturation in the course of the seizure with a postictal maximum whereas contralateral findings were inconsistent. The favourable outcome of selective amygdalahippocampectomy in both cases retrospectively confirmed the correct lateralization by video-EEG and the concordant NIRS findings. Our preliminary results suggest that NIRS might be a simple, cost-effective and non-invasive additional method to lateralize the primary epileptogenic zone in temporal lobe epilepsy and should be further investigated in larger series of patients.

Homocysteine and alcoholism

Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is growing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by stimulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism.

First clinical experiences with perampanel—The Kork experience in 74 patients

Perampanel (PER) has been approved for adjunctive treatment of partial‐onset seizures in patients age 12 years and older. In Germany, PER was licensed and marketed in September of 2012. At our tertiary referral epilepsy center, a couple of difficult‐to‐treat patients were awaiting this introduction of PER; therefore, we were able to initiate treatment in many patients within a short period of time. For this report we collected and analyzed the data of the first patients who had been started on add‐on PER between September and December of 2012, so that we were able to evaluate at least 6 months of treatment when we made this analysis. At cutoff in June of 2013, 74 patients could be analyzed. Mean age was 38.4 years (range 15–71 years). PER doses ranged from 4 to 14 mg (mean 8.8 mg). All patients took PER once daily at bedtime. Seventy‐one patients had focal epileptic seizures; the remaining four patients had Lennox‐Gastaut syndrome. Considering the last 3 months of observation compared with baseline, 34 patients (46%) were responders with a reduction of seizure frequency of at least 50%. Ten patients of these (14% of all) were seizure‐free. Adverse events were reported in 40 patients (54%). Leading side effects were somnolence (n = 31, 42%) and dizziness (n = 13, 18%), followed by ataxia, irritability, falls, cognitive slowing, and depression in single cases. Six‐month retention rate was 70%. Our first clinical experiences with add‐on PER in a highly selected group of difficult‐to‐treat epilepsies are promising.

Abnormal response of motor cortex to photic stimulation in idiopathic generalized epilepsy.

Background:  Intermittent photic stimulation (IPS) shortens the cortical silent period (CSP) elicited by transcranial magnetic stimulation (TMS) over the primary motor hand area (M1HAND). This response is absent in healthy individuals with a photoparoxysmal response (PPR). Here we combined TMS of the M1HAND with IPS to examine whether patients with idiopathic generalized epilepsy (IGE) exhibit an abnormal cortical response pattern to IPS.

Risk assessment of alcohol withdrawal seizures with a Kohonen feature map.

Recently, it has been suggested that alcohol-induced hyperhomocysteinaemia in patients suffering from chronic alcoholism might be a risk factor for alcohol withdrawal seizures. In the present follow-up study 12 patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine (Hcy) on admission (71.43 ± 25.84 mol/l) than patients (n = 37) who did not develop seizures (32.60 ± 24.87 mol/l; U = 37.50, p = 0.0003). Using a logistic regression analysis, withdrawal seizures were best predicted by a high Hcy level on admission (p < 0.01; odds ratio 2.07). Based on these findings we developed an artificial neural network system (Kohonen feature map, KFM) for an improved prediction of the risk of alcohol withdrawal seizures. Forty-nine patients with chronic alcoholism (12 with alcohol withdrawal seizures and 37 without seizures) were randomized into a training set and a test set. Best results for sensitivity of the KFM was 83.3% (five of six seizure patients were predicted correctly) with a specificity of 94.4% (one false positive prediction of 19 patients). We conclude that in patients with alcohol-induced hyperhomocysteinaemia the KFM is a useful tool to predict alcohol withdrawal seizures.

SURFACE EMG AND MYOSONOGRAPHY IN THE DETECTION OF FASCICULATIONS : A COMPARATIVE STUDY

Surface electromyography (EMG) and muscle sonography both facilitate the detection of fasciculations. This study was conducted to evaluate the prevalence of fasciculations in 10 lower extremity muscles in 58 subjects 47 ± 18 years of age without and 54 patients 52 ± 15 years of age with various neuromuscular diseases (3 with inflammatory myopathy, 15 with lower motor neuron disease, 22 with acquired and 11 with hereditary motor and sensory neuropathy (HMSN), and 3 with adrenomyeloneuropathy). When each muscle was screened by means of myosonography for 10 seconds, fasciculations were found in up to 8 muscles in 11 control subjects (19%) and in up to 10 muscles in 41 patients (76%). Within the same recording period surface EMG revealed fasciculations in 5 control subjects (9%) and 30 patients (56%), whereas during a recording time of 20 minutes fasciculations were detected in 55 (95%) control subjects and all patients. An amplitude of 400 µV proved to be the optimum cutoff between fasciculations for healthy subjects and patients with neuromuscular disease (accuracy, 74%). Myosonography allowed differentiation of both groups with an accuracy of 79%. Surface EMG was more liable to artifacts than myosonography. The average interval between subsequent fasciculations cannot be used to differentiate patients with acquired and hereditary polyneuropathy and with lower motor neuron disease. Long‐term surface EMG recording indicates fasciculations to occur in almost all patients with neuromuscular disease and the vast majority of healthy subjects. Muscle ultrasonography was more convenient and reliable than surface EMG in differentiating patients and healthy subjects.

The Lateralizing Value of Ictal Clinical Symptoms in Uniregional Temporal Lobe Epilepsy

In order to assess the lateralizing value of several ictal and postictal clinical symptoms in temporal lobe epilepsy (TLE), we analyzed 89 seizures of 20 left dominant patients with intractable left (n = 9) versus right (n = 11) TLE who had undergone successful anterior temporal lobectomy. In left TLE, movement arrest at seizure onset, postictal dysphasia >120 s and postictal dyslexia >180 s were the most typical findings and associated with a sensitivity of 94, 94, and 100%, respectively. The highest specificity of 100% each was evident for contralateral versions of eyes and head and dystonic posturing. In right TLE, the highest sensitivity was seen for whole-body movements at seizure onset, postictal dysphasia <120 s and postictal dyslexia <180 s with figures of 82, 87, and 93%, respectively. As compared to left TLE, contralateral version and dystonic posturing, ictal speech, and postictal dyslexia <180 s each had a specificity of 100%. The careful combined analysis of certain ictal clinical signs combined with consistent findings of interictal EEG and neuroimaging studies may be often sufficient to proceed with epilepsy surgery without invasive recordings even if ictal scalp EEG is not unambiguous.

Fixation-off sensitivity in an adult with symptomatic occipital epilepsy

Summary: An adult patient had EEG occipital spike fixation‐off sensitivity and spontaneous occipital seizures due to perinatal asphyxia with bioccipital hemorrhage. EEG abnormalities consisted of repetitive posterior spikes that occurred when the eyes were closed and other conditions of fixation‐off. Magnetic resonance imaging (MRI) documented severe posterior lesions with wallerian degeneration of the optic radiation. Electron capture detector single‐photon emission computed tomography (ECD‐SPECT) during the state of fixation‐off showed regional hyperperfusion in the right posterior regions. We suggest that partial denervation of the primary visual cortex in this patient resulted in an increased cortical excitability and that the inhibitory effect of central vision and fixation leads to a suppression of spontaneous epileptic activity. This unusual symptomatic case may serve as a model for the pathophysiology in the more often reported cases of idiopathic benign epilepsy syndrome of childhood.