Karsten Krakow

Linking Generalized Spike-and-Wave Discharges and Resting State Brain Activity by Using EEG/fMRI in a Patient with Absence Seizures

Summary:  Purpose: To illustrate a functional interpretation of blood oxygen level–dependent (BOLD) signal changes associated with generalized spike‐and‐wave discharges in patients with absence seizures and to demonstrate the reproducibility of these findings in one case.

Levetiracetam Intravenous Infusion as an Alternative to Oral Dosing in Patients with Partial‐Onset Seizures

Summary:  Purpose: This multicenter, open‐label study evaluated the short‐term tolerability of intravenously (IV)‐infused levetiracetam (LEV; 500–1,500 mg/100 ml, 15 min, b.i.d.) as a substitute for the same oral dose.

Arousal thresholds during human tonic and phasic REM sleep.

The goal of the present study was to investigate arousal thresholds (ATs) in tonic and phasic episodes of rapid eye movement (REM) sleep, and to compare the frequency spectrum of these sub‐states of REM to non‐REM (NREM) stages of sleep. We found the two REM stages to differ with regard to behavioural responses to external acoustic stimuli. The AT in tonic REM was indifferent from that in sleep stage 2, and ATs in phasic REM were similar to those in slow‐wave sleep (stage 4). NREM and REM stages of similar behavioural thresholds were distinctly different with regard to their frequency pattern. These data provide further evidence that REM sleep should not be regarded a uniform state. Regarding electroencephalogram frequency spectra, we found that the two REM stages were more similar to each other than to NREM stages with similar responsivity. Ocular activity such as ponto‐geniculo‐occipital‐like waves and microsaccades are discussed as likely modulators of behavioural responsiveness and cortical processing of auditory information in the two REM sub‐states.

Effects of antiepileptic drugs on associative LTP-like plasticity in human motor cortex

Antiepileptic drugs (AEDs) are used extensively in clinical practice but relatively little is known on their specific effects at the systems level of human cortex. Here we tested, using a double‐blind randomized placebo‐controlled crossover design in healthy subjects, the effects of a single therapeutic oral dose of seven AEDs with different modes of action (tiagabine, diazepam, gabapentin, lamotrigine, topiramate, levetiracetam and piracetam) on long‐term potentiation (LTP)‐like motor cortical plasticity induced by paired associative transcranial magnetic stimulation (PAS). PAS‐induced LTP‐like plasticity was assessed from the increase in motor evoked potential amplitude in a hand muscle contralateral to the stimulated motor cortex. Levetiracetam significantly reduced LTP‐like plasticity when compared to the placebo condition. Tiagabine, diazepam, lamotrigine and piracetam resulted in nonsignificant trends towards reduction of LTP‐like plasticity while gabapentin and topiramate had no effect. The particularly depressant effect of levetiracetam is probably explained by its unique mode of action through binding at the vesicle membrane protein SV2A. Enhancement of gamma‐amino butyric acid‐dependent cortical inhibition by tiagabine, diazepam and possibly levetiracetam, and blockage of voltage‐gated sodium channels by lamotrigine, may also depress PAS‐induced LTP‐like plasticity but these mechanisms appear to be less relevant. Findings may inform about AED‐related adverse effects on important LTP‐dependent central nervous systems processes such as learning or memory formation. The particular depressant effect of levetiracetam on LTP‐like plasticity may also relate to the unique properties of this drug to inhibit epileptogenesis, a potentially LTP‐associated process.

fMRI correlates of interictal epileptic activity in patients with idiopathic benign focal epilepsy of childhood. A simultaneous EEG-functional MRI study.

Summary EEG-correlated fMRI (EEG/fMRI) can identify alterations of brain function associated with interictal epileptiform discharges (IED). fMRI activation can localize the irritative zone and indicate functional disturbance distant from the spike focus. This might be of particular interest in paediatric epilepsy syndromes with frequent IED. Using simultaneous EEG/fMRI in a 3T MR scanner we studied blood oxygen level-dependent (BOLD) signal changes related to spontaneous IED in 10 children with typical and atypical benign focal epilepsy of childhood (BFE) or benign epileptic activity of childhood (BEAC). EEG artefacts were subtracted offline and IED were used as regressors for event-related fMRI analysis in SPM2. In four of the seven children with IED during EEG/fMRI we found IED related positive and negative signal changes ( p p In addition to former reports our results indicated that frontal brain areas are functionally disturbed during IED corresponding to general neuropsychological findings in BFE and BEAC. We conclude that using EEG/fMRI it might be possible to localize generators of IED and functionally disturbed brain regions in children with BFE. Further studies are required to differentiate between BFE subtypes and to identify fMRI signatures of specific syndromes or corresponding neuropsychological deficits.

Handwriting analysis for diagnosis and prognosis of parkinson's disease

At present, there are no quantitative, objective methods for diagnosing the Parkinson disease. Existing methods of quantitative analysis by myograms suffer by inaccuracy and patient strain; electronic tablet analysis is limited to the visible drawing, not including the writing forces and hand movements. In our paper we show how handwriting analysis can be obtained by a new electronic pen and new features of the recorded signals. This gives good results for diagnostics.

Predictors of Acute Poststroke Seizures

Background: In this study, we tried to identify predictors of acute poststroke seizures (aPSS) in stroke patients. Methods:We analyzed a large prospective hospital-based stroke registry in Germany. 58,874 patients with the diagnosis of transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH) were admitted within 24 h after symptom onset. Predictors for aPSS were identified using multivariate regression analysis adjusted for age, gender, stroke severity, vascular risk factors, acute nonneurologic infection, history of TIA and length of hospital stay. Results: aPSS occurred in 0.7% of patients with TIA (mean duration of hospitalization 8 days), in 2.2% of patients with IS (12 days) and in 5.1% of patients with ICH (13 days). A lower age, a higher stroke severity, acute nonneurologic infection, a history of diabetes mellitus and a history of preceding TIA were identified to be independent predictors of aPSS in IS, whereas younger age, acute infection and a history of TIA were found predictive for aPSS in ICH. Conclusions: This study characterized so far unknown predictors of aPSS and may help to improve the identification of patients with a high risk of aPSS.

Intraoperative Ultrasound to Define Focal Cortical Dysplasia in Epilepsy Surgery

Focal cortical dyplasia (FCD) is a frequent cause of medication‐resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize.

Imaging Epileptic Activity Using Functional MRI

This review concentrates on functional MRI (fMRI) methods to identify the epileptic focus, i.e. ictal and interictal fMRI. First, established clinical applications of fMRI in the field of epilepsy are briefly introduced: fMRI of sensorimotor, language and memory function can already be considered as clinically relevant tools to identify the eloquent cortex and to predict postoperative functional deficits in patients considered for epilepsy surgery. fMRI offers a valid alternative to invasive methods like the Wada test for establishing language dominance, and it is likely that it will also replace the Wada test for assessing presurgical memory function in the nearer future. Ictal fMRI (fMRI studies of epileptic seizures) will remain confined to exceptional cases due to practical limitations. The generators of interictal epileptiform discharges (IED) can be studied with EEG-correlated fMRI. Despite its technical challenges, it has proved useful to provide insights into the generation of IED in patients with focal and generalized epilepsy. In selected patients with focal IED, EEG-correlated fMRI has the potential to reproducibly identify cortical areas involved in generating IED, i.e. the irritative zone. In patients with generalizes IED, suspension of functional networks due to the IED can be demonstrated. The utility of EEG-correlated fMRI in clinical epileptology cannot be definitely determined yet.

Presurgical Functional MRI in Patients with Brain Tumors

Neurosurgery in functionally important brain sites carries a high risk for surgery induced neurological deficits. In patients with brain tumors fMRI facilitates the selection of a safe treatment and to plan and perform function preserving surgery. However, fMRI has not yet reached the status of an established and standardized diagnostic neuroimaging procedure and still needs to be performed in clinical research trials. Preoperative fMRI is performed exclusively in individual patients and therefore differs fundamentally from research applications in the neurosciences.