[Invasive neurostimulation as adjunct treatment for epilepsy]. / Invasive Neurostimulation in der Epilepsietherapie.

Neurostimulation techniques are applied to reduce the frequency and severity of epileptic seizures. Class I evidence showed that vagus nerve stimulation (VNS) reduces seizure burden by 25-28% compared to 6-15% in placebo controls. Open-label studies, however, reported much greater efficacy. Since 2010 deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is CE approved for epilepsy therapy in Europe. A multicenter randomized controlled trial reported seizure frequency reduction by 40.4% compared to 14.5% in controls. A significant effect was only found in patients with temporal seizure onset. 13% of stimulated patients became seizure-free for at least 6 months. Possible side-effects include depression (14.8%) and memory impairment (13%). Responsive neurostimulation (RNS) combines an automated seizure detection device with on-demand triggered stimulation of the epileptogenic zone. A randomized controlled trial reported seizure frequency reduction by 37.9% compared to 17.3% in controls. There were no relevant neuropsychological or psychiatric side-effects noted.

Visual naming performance after ATL resection: impact of atypical language dominance.

PURPOSE: To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL). METHODS: Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus. RESULTS: Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size=0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n=14; p<0.05), but did not reach statistical significance in patients with left language dominance (n=36; p=0.09). Chi-square test revealed a trend of higher proportions of patients experiencing significant postsurgical deterioration in naming performance in atypical (57.1%) as compared to left language dominance (30.6%; p=0.082). Surgical failure was also associated with greater decline of BNT scores and was more common in atypical than in left language dominant patients (chi(2) (1, n=98)=4.62, p=0.032). Age of onset, duration of epilepsy, and seizure frequency had no impact on changes in BNT performance. CONCLUSION: Atypical language dominance is a predictor of change in visual naming performance after left ATL and may also impact postsurgical seizure control. This should be considered when counseling surgical candidates.

Memory performance is related to language dominance as determined by the intracarotid amobarbital procedure.

OBJECTIVE: The goal of this study was to explore the relationship between language and memory lateralization in patients with epilepsy undergoing the intracarotid amobarbital procedure. METHODS: In 386 patients, language lateralization and memory lateralization as determined by laterality index (LI) were correlated with each other. RESULTS: Language lateralization and memory lateralization were positively correlated (r=0.34, P<0.01). Correlations differed depending on the presence and type of lesion (chi(2)=7.98, P<0.05). LIs correlated significantly higher (z=2.82, P<0.05) in patients with cortical dysplasia (n=41, r=0.61, P<0.01) compared with the group without lesions (n=90, r=0.16, P>0.05), with patients with hippocampal sclerosis falling between these two groups. Both memory (P<0.01) and language (P<0.01) LIs were higher in right- compared with left-sided lesions. CONCLUSION: Correlation of language and memory is more pronounced in patients with structural lesions as compared with patients without lesions on MRI.

Intravenous levetiracetam: a new treatment alternative for refractory status epilepticus.

The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam (LEV-iv) in refractory status epilepticus (SE). A retrospective chart review was performed on patients who received LEV-iv for treatment of SE (n = 36) and had failed at least one other antiepileptic drug. LEV-iv (median 3000 mg/day; range 1000-9000) was administered as a bolus loading (500-2000 mg per 30-60 min, n = 30) or as a continuous pump infusion (n = 6). SE was terminated in 69% ("responders"); 31% ("non-responders") remained in SE. Factors associated with failure were: dose escalation over 3000 mg/day, lack of bolus loading, treatment latency over 48 h, age over 80 years, non-convulsive SE with coma ("subtle SE"), periodic lateralised epileptiform discharges (PLEDs) on EEG, acute cerebral lesion and intubation narcosis. SE was terminated in all eight patients without brain lesion (p = 0.033), and in all seven patients with complex partial SE (p = 0.051). Outcome was favourable (ambulatory patients) in 48% (responders) compared with 0% (non-responders), and "adverse" (death or continuing coma/stupor) in 24% (responders) compared with 100% (non-responders). Mortality was 17% (responders 4%, non-responders 45%). No patient had cardiocirculatory side effects or worsening of SE. Two patients experienced nausea and vomiting during LEV-iv loading, leading to aspiration pneumonia in one. This study suggests that LEV-iv may be a safe and efficacious treatment of SE. Prospective and controlled trials are imperative to confirm these preliminary findings.

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. OBJECTIVE: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. METHODS: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor "group," covariate "age"). RESULTS: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. CONCLUSIONS: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI.

Frequency of seizures and epilepsy in neurological HIV-infected patients.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. METHODS: The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. RESULTS: Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse. CONCLUSIONS: Seizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group.

[Refractory status epilepticus: diagnosis, therapy, course, and prognosis]. / Therapierefraktärer Status epilepticus: Diagnostik, Therapie, Verlauf und Prognose.

Status epilepticus (SE) is a frequent neurological emergency with an annual incidence of 10-20/100,000 individuals. The overall mortality is about 10-20%. Patients present with long-lasting fits or series of epileptic seizures or extended stupor and coma. Furthermore, patients with SE can suffer from a number of systemic complications possibly also due to side effects of the medical treatment. In the beginning, standardized treatment algorithms can successfully stop most SE. A minority of SE cases prove however to be refractory against the initial treatment and require intensified pharmacologic intervention with nonsedating anticonvulsive drugs or anesthetics. In some partial SE, nonpharmacological approaches (e.g., epilepsy surgery) have been used successfully. This paper reviews scientific evidence of the diagnostic approach, therapeutic options, and course of refractory SE, including nonpharmacological treatment.

[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.

[Electric brain stimulation for epilepsy therapy]. / Elektrische Hirnstimulation in der Epilepsietherapie.

Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50 years. Many different stimulation targets and methods have been investigated. Vagal nerve stimulation (VNS) is now approved for the treatment of refractory epilepsies by several governmental authorities in Europe and North America. However, it is mainly used as a palliative method when patients do not respond to medical treatment and epilepsy surgery is not possible. Numerous studies of the effect of deep brain stimulation (DBS) on epileptic seizures have been performed and almost invariably report remarkable success. However, a limited number of controlled studies failed to show a significant effect. Repetitive transcranial magnetic stimulation (rTMS) also was effective in open studies, and controlled studies are now being carried out. In addition, several uncontrolled reports describe successful treatment of refractory status epilepticus with electroconvulsive therapy (ECT). In summary, with the targets and stimulation parameters investigated so far, the effects of electrical brain stimulation on seizure frequency have been moderate at best. In the animal laboratory, we are now testing high-intensity, low-frequency stimulation of white matter tracts directly connected to the epileptogenic zone (e.g., fornix, corpus callosum) as a new methodology to increase the efficacy of DBS ("overdrive method").

Background potassium concentrations and epileptiform discharges. I. Electrophysiological characteristics of neuronal activity.

Intra- and extracellular recording techniques were used to study the epileptiform activity generated by guinea pig hippocampal slices perfused with free-magnesium artificial cerebrospinal fluid in the presence of physiologic (4 mM), reduced (2 mM) or elevated (8 mM) extracellular potassium concentrations ([K(+)](o)). Extracellular field potentials along with intracellular recordings were recorded in CA1 or CA3 region. Reduction of [K(+)](o) significantly increased the latency of epileptiform field potential (EFP) appearance as well as burst discharge duration and decreased EFP repetition rate. Depending on different background [K(+)](o), epileptiform burst discharges appeared in different patterns including varied types of paroxysmal depolarisation shifts and burst activity in CA1 and CA3 subfields. Comparison with physiological and increased [K(+)](o,) reduction of [K(+)](o) significantly increased the mean duration of bursts, mean amplitude of depolarisation, mean after-hyperpolarisation duration, and inter-spike intervals in both CA1 and CA3 areas. Three distinct patterns were distinguished on the basis of their evoked firing pattern in response to application of depolarising current pulses in the interval of epileptiform burst discharges. Neurons superfused with 2 mM [K(+)](o) presented fast adapting pattern while cells washed with 4 or 8 mM [K(+)](o) exhibited intrinsically bursting or slow adapting patterns. Comparing the groups with different background [K(+)](o), there is a more severe form of discharges in low K(+) and a subtle difference between 4 and 8 mM K(+). The data indicate the importance of background [K(+)](o) on epileptiform burst discharge pattern and characteristics.

Background potassium concentrations and epileptiform discharges. II. Involvement of calcium channels.

Potassium- and calcium conductances regulate neuronal excitability and epileptiform activity. In this study, the effects of different extracellular potassium concentrations ([K(+)](o)) were investigated on the modulatory effect of the L-type transmembranous calcium currents on epileptiform discharges. The in vitro brain slice technique was used to examine the effects of calcium channel blockers, verapamil and nifedipine, on the repetition rate, amplitude, and duration of epileptiform field potentials (EFP) in the presence of low, physiological, and high background [K(+)](o) in guinea pig hippocampal slices. Epileptiform activity was induced by omission of Mg(2+) from artificial cerebrospinal fluid contained 2, 4, and 8 mM [K(+)](o). Both verapamil and nifedipine suppressed EFP after a transient increase in repetition rate. The extent of EFP frequency rate acceleration significantly increased with reduction of [K(+)](o). The increase in EFP frequency rate induced by application of verapamil and nifedipine was accompanied by a reduction in the EFP amplitude and a reversible increase in the burst discharge duration. The extent of burst discharge prolongation was also significantly higher with decreasing [K(+)](o). Further application of verapamil and nifedipine suppressed the epileptiform burst activity in the presence of different [K(+)](o). The latency of EFP depression was significantly diminished both with increased and decreased background potassium concentrations. The data indicate the importance of the effect of the L-type transmembranous calcium currents on the regulatory effect of background [K(+)](o) on epileptiform burst discharge frequency and duration.

Fractional bandwidth normalization for optical spectra with application to the solar blackbody spectrum.

Optical spectra are typically normalized per unit wavelength or per unit photon energy, yielding two different expressions or curves. It is advantageous instead to normalize a spectrum to a constant fractional bandwidth, providing a unique expression independent of whether the bandwidth is in dimensions of wavelength or of photon energy. For the Sun, whereas a per-unit-wavelength spectrum peaks in the green and a per-unit-photon-energy spectrum peaks in the IR, when the proposed normalization is used, the output peaks in the red. This approach applies to any spectral source and provides curves of constant spectral resolving power, as produced by many spectrometers.

Fixed polarizer ellipsometry for simple and sensitive detection of thin films generated by specific molecular interactions: applications in immunoassays and DNA sequence detection.

Biological thin films may form on a surface by specific molecular interactions. The fixed polarizer ellipsometer (FPE) is a sensitive instrument that detects biological thin films either qualitatively or quantitatively. The design is simple and inexpensive. The assays are formatted on an optical surface, and the FPE detection is based on the phase shift of linearly polarized light after reflection through a thin film. We have constructed mathematical models of the FPE response to reflection through single-layer and two-layer films that agree closely with experimental data. Several biological assays have been measured with the FPE to demonstrate the application of this technology to clinical targets, including ultrasensitive immunoassays for hepatitis B surface antigen (0.1 ng/mL) and alpha-fetoprotein (0.01 ng/ mL) and DNA hybridization (0.5 fmol/microL target probe). A clinical study for detection of group A streptococcus from patient throat swabs demonstrated the qualitative application of the FPE to infectious disease targets. The flexibility and sensitivity of the FPE makes this technology suitable for numerous target analytes and applications.

Fringe visibility improvement using an asynchronous image-subtracting optically addressed spatial light modulator.

We demonstrate the application of an asynchronous image-subtraction optically addressed spatial light modulator to particle image velocimetry fringe processing. The device comprises an amorphous silicon p-i-n-i-p photosensor and a ferroelelectric liquid-crystal light-modulating layer. The images to be subtracted are encoded on two separate wavelengths. The operation of the device is described, and characterization shows a frame rate of 100 Hz, a resolution of 3 line pairs/mm, and a write-light sensitivity of ≈1 mW/cm(2) at a wavelength of 514 nm. The device is read by the use of light with a 633-nm wavelength whereas the subtraction light is at a wavelength of 670 nm. Using this device to subtract a nonuniform pedestal from the optically computed power spectral density function (the Young's fringe pattern), we find we can improve the signal-to-clutter ratio of peaks in the image-transmittance autocorrelation function of particle image velocimetry transparencies. The device also permits processing of very low-visibility fringe patterns, generated from doubly exposed images, in which one image has half the transmittance of the other. These could not be processed with a nonsubtracting, binary, liquid-crystal optically addressed spatial light modulator.

Effects of charge spreading on resolution of optically addressed spatial light modulators.

A transient charge-transport model is developed to evaluate the resolution limits of optically addressed spatial light modulators. The effect of bulk charge diffusion on resolution is largely independent of the mobility in the semiconductor layer, and the resolution is limited by the lateral diffusion length of charge carriers in transit. The effects of charge drift, diffusion, and trapping at the interface between the semiconductor and the lightmodulating layer depend strongly on the interface properties. The resolution ranges from 2 to 700 line pairs/mm for respective diffusion lengths of 16.1 to 0.16 microm at the interface.

Alignment layers for improved surface-stabilized ferroelectric liquid-crystal devices.

Ultrathin silane monolayer and silicon oxide alignment layers in surface-stabilized ferroelectric liquidcrystal devices are shown to enhance bistability and reduce degradation from ions.

Integrating mode for an optically addressed spatial light modulator.

We describe the integrating-mode operation of an optically addressed spatial light modulator that incorporates a ferroelectric liquid-crystal light-modulating layer and an amorphous-silicon photodiode. This mode of operation uses a higher drive frequency and produces a readout response that extends over several driving periods, thereby permitting cw operation. The response characteristics of the device can be adjusted by varying the amplitude and offset of the applied voltage. Spatial resolution of 40 line pairs/mm, response times of 1 ms, and contrast ratios of 30:1 were achieved in this mode. We compare the integrating mode of operation with our standard reset mode of operation, whereby the electrical driving frequency is sufficiently low that the liquid crystal can respond fully to the voltage level during each part of the drive, and the device is reset fully to its off state during the forward-bias part of each electrical bias period.

Hydrogenated amorphous silicon photodiodes for optical addressing of spatial light modulators.

We discuss the use of hydrogenated amorphous silicon (a-Si:H) photodiodes as photosensors in high-performance optically addressed spatial light modulators (OASLM's). To find the performance limitations that result from the photodiode exclusively, a pseudo-OASLM is constructed; it is composed of an a-Si:H photodiode in series with a discrete capacitor and resistor to simulate an electrically ideal liquid-crystal modulator. The a-Si:H photodiode conduction regimes are identified, and the maximum and minimum frame rates that may be attained with an a-Si:H photodiode-driven OASLM are determined to be ~ 100 kHz and ~ 0 Hz, respectively. Optimum performance is obtained when the photodiode capacitance is equal to the light modulator capacitance.