Source reconstruction of mesial-temporal epileptiform activity: comparison of inverse techniques.

PURPOSE: To evaluate whether advanced source reconstruction such as current density reconstruction (CDR) provides additional hints for clinical presurgical evaluation, different source reconstruction techniques with idealized spherical as well as realistically shaped head models (boundary element method, BEM) were applied on interictal and ictal epileptiform activity in presurgical evaluated patients with temporal lobe epilepsy. It is discussed whether CDR and BEM give additional information for presurgical evaluation compared to "conventional" strategies, such as single moving, and spatio-temporal dipole modeling with spherical head models. METHODS: A variety of source reconstruction procedures were applied to the data of five patients with pharmacoresistent temporal lobe epilepsy with probable mesial origin: (1) single-moving dipole in a spherical head model and (2) in BEM, (3) spatio-temporal dipole modeling in a spherical head model and (4) in BEM; and (5) deconvolution with fixed locations and orientations and (6) with cortically constrained L1-norm CDR in BEM. In addition, simulated sources of temporal lobe origin were calculated in each subject with CDR to prove the basic feasibility of this technique in the particular application. RESULTS: Source activity was correctly localized within the affected temporal lobe by all source reconstruction techniques used. Neither single moving dipole, spatio-temporal modeling, nor CDR was able to localize sources at a sublobar level. In the case of two sources, single moving dipole solutions showed changes in dipole orientation in time and spatio-temporal modeling separated two sources, whereas CDR at the peak latency failed to distinguish among different origins. BEM enhanced localization accuracy. CONCLUSION: There was no advantage of using CDR. Single moving dipole as well as spatio-temporal dipole modeling in BEM leads to more precise localization within the individual anatomy and provides a simple algorithm, which is capable of indicating both the time course and the number of sources.

Blood flow velocities in middle cerebral artery branches after subarachnoid hemorrhage.

In a prospective study, 55 patients were examined by transcranial duplex sonography (TCCS) after subarachnoid hemorrhage (SAH) to determine whether additional transcranial duplex examination on the middle cerebral artery M2 segments would aid in the examination of the MCA stem segment. The mean blood flow velocities and pulsatility index were correlated to the occurrence of delayed ischemic neurologic deficits (DIND). Out of 47 patients included, 21 did not experience any delayed deficit (group I), 15 did (group II), and in 11 the extent to which vasospasm contributed to a neurologic deficit was unclear (group III). The highest blood flow velocity and the greatest increase of mean blood flow velocity on 1 day were significantly higher in groups II and III both in M1 and in M2. In 10 patients in group II, where the onset day of DIND was known exactly, Doppler data indicating ischemia before or at the time of DIND were observed in nine. In eight patients, Doppler of the MCA stem alone would have provided enough information to recognize the risk of symptomatic vasospasm; in one patient, only the M2 Doppler gave an indication of ischemic complication. Transcranial duplex sonography may provide additional information to TCD by accurate delineation of M1/M2 vasospasm and therefore may help plan cerebral angiography and neurointerventional treatment.

Dipole-source analysis in a realistic head model in patients with focal epilepsy.

PURPOSE: By the use of three different head models in EEG dipole analysis, we tried to model the origin of interictal and ictal epileptic activity as precisely as possible. Further, as a control, a second evaluation was made by an independent group to control for interindividual reliability of the dipole source analysis. With the realistic head model (CURRY) considering cortex, skull, and skin segmentation, the spike source was located. METHODS: In five patients with mesial temporal epileptogenesis, confirmed by successful epilepsy surgery, the spike source was close to the hippocampus, with a mean distance of the dipole source from the hippocampus of 13.6 mm (range, 9-17.2 mm). In one case the ictal EEG also could be analyzed and resulted in a dipole-source localization comparable to the interictal source. RESULTS: In both head models using either pure cortex segmentation only or a concentric three-shell model, the dipole source was systematically dislocated in a more superior position. Data analysis by a second group with independently chosen EEG samples and identical individual head model resulted in deviations of <5.3 mm. Data analysis using independently selected spikes and independently segmented head models resulted in deviations < or =16.7 mm. CONCLUSIONS: In four cases of extratemporal epileptogenesis, the origin of interictal epileptiform discharges was localized to the suspected primary epileptogenic zone.

Cisternal S100 protein and neuron-specific enolase are elevated and site-specific markers in intractable temporal lobe epilepsy.

In the brain, S100 protein and neuron-specific enolase (NSE) are mainly found in glial cells and neurons, respectively. We investigated concentrations of S100 protein and NSE in cisternal cerebrospinal fluid obtained during implantation of foramen ovale electrodes in eight patients with temporal lobe epilepsy (TLE). In addition, the meningeal markers cystatin-C and beta-trace as well as total protein were measured. Patients with trigeminal neuralgia (TN) undergoing glycerol rhizotomy served as controls. S100 protein and NSE levels ipsilateral to the site of seizure onset were significantly higher than in TN. Contralateral TLE values were also markedly but not significantly elevated. The meningeal markers cystatin-C and beta-trace protein as well as total protein did not differ in TLE and TN. We conclude that interictal temporal lobe dysfunction corresponds with neuronal and glial marker elevations in the extracellular space and that site-specific elevations may predict the site of seizure origin biochemically.

Kinetics of serum neuron-specific enolase and prolactin in patients after single epileptic seizures.

PURPOSE: To investigate and compare the temporal profile of serial levels of neuron-specific enolase (NSE) and prolactin in serum from patients after single epileptic seizures. METHODS: Measurement of NSE and prolactin by sensitive immunoassays in 21 patients with complex partial seizure (CPSs: n = 11) and secondarily generalized tonic-clonic seizures (SGTCSs; n = 10) during continuous video-EEG monitoring at four different time points (1, 3, 6, and 24 h after ictal event). Statistical analysis was performed by using a repeated-measures analysis of variance (ANOVA) model. RESULTS: Mean+/-SD values for NSE levels (ng/ml) were 12.5 +/-4.4 (1 h), 10.8+/-3.8 (3 h), 11.1+/-4.9 (6 h), and 8.2+/-1.9 (24 h). The corresponding prolactin levels (mU/L) were 1,311+/-1,034, 232+/-158, 237+/-175, and 251+/-98. There was a significant decrease of NSE and prolactin levels over time (p < 0.001). The pair-wise comparison of NSE levels showed significant differences between the time points 1 vs. 24 h (p < 0.001), 3 vs. 24 h (p = 0.007), and 6 vs. 24 h (p = 0.009). In contrast, serum prolactin levels showed a significant difference between 1 vs. 3 h (p < 0.001) only. Most of the NSE levels remained normal after CPSs and SGTCSs. At 1 h after the seizure, only 33% of the subjects had increased NSE, whereas abnormal prolactin levels occurred with a sensitivity of 80%. CONCLUSIONS: In contrast to prolactin, serum NSE is not a sensitive marker of individual seizures. Only some individuals showed an increase of NSE beyond the prolactin-sensitive time frame after a single seizure, and mean NSE levels were not significantly increased compared with those of normal controls.

[Elecroencephalographic charactistics of Creutzfeldt-Jakob disease and its differential diagnosis]. / Elektroenzephalographische Charakteristika der Creutzfeldt-Jakobschen Krankheit und ihre Differentialdiagnose.

Although clinical electroencephalography is no longer as important as it used to be in differential diagnosis of a fair number of neurological and psychiatric diseases ever since imaging techniques have been making enormous strides, EEG is still an important diagnostic tool in dementias where specific morphological lesions are not immediately or not at all apparent which would otherwise be visible by imaging. Sporadic Creutzfeldt-Jakob disease is an important case in point. Although this is associated with some unspecific EEG findings, typical periodical sharp wave complexes (PSWC) become conspicuous in the course of the disease. If these are meticulously studied and particular attention is paid to their periodicity, a sensitivity of 67% and a specificity of 86% are attained. With the exception of one familial variant of Creutzfeldt-Jakob disease PSWC ar usually absent all other human prion diseases. Hence, it is not likely that they are linked to the aetiology of sporadic Creutzfeldt-Jakob disease. We present a patho-physiological hypothesis on the development of PSWC basing on the assumption that the specific periodicity of PSWC results from a still functionally active but greatly impaired subcortical-cortical circuit of neuronal excitability. This specific pattern of neuronal degeneration may obviously arise--albeit very rarely--also in other diseases independent of their aetiology, so that the EEG patterns appear identical. For this reason it is imperative to make complementary use of EEG and of recent clinical and laboratory data of Creutzfeldt-Jakob disease before PSWC and be considered a relevant diagnostic criterion. Conversely, clinical diagnosis of Creutzfeldt-Jakob disease should be reconsidered if repeated EEG recordings fail to reveal PSWC even under technically adequate conditions.

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 microV 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.

Isolated ataxia as an idiosyncratic side-effect under gabapentin.

Gabapentin has been accepted worldwide as a novel antiepileptic drug with a favourable tolerability profile. However, movement disorders have been reported previously as rare side-effects in individual patients. We report on two patients who developed isolated severe ataxia under low-dose gabapentin which resolved abruptly after discontinuation of the drug. This side-effect probably resembled a rare idiosyncratic adverse reaction. We propose the gabapentin-specific neuronal binding site which has a high density in the cerebellum as a possible mechanism of action and suggest that the initiation of gabapentin requires caution if pre-existing cerebellar function impairment is evident.

Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia.

Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subject, (age 27.2 +/- 0.7 years) after either a single intravenous administration of 25 mg doxepin or placebo in a randomized, double blind, and cross-over setting. In the patient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients on the healthy subjects. After three weeks of oral doxepin intake by the patients, the area under the curve of total nocturnal plasma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatment as well as after long-term oral administration, doxepin also significantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturnal wake time was decreased. These findings indicate that this tricyclic antidepressant not only improves sleep and but also preserves the secretion of a hormone which is believed to play a special role in the circadian sleep-wake rhythm. Long-term doxepin treatment of chronic insomniac patients not only improves sleep but also restores nocturnal melatonin secretion in these patients.

[Ambulatory, comprehensive, behavior therapy-oriented weight reduction program (Optifast Program). An alternative therapy in obstructive sleep apnea]. / Die ambulante, ganzheitliche, verhaltenstherapeutisch orientierte Gewichtsreduktion (Optifast-Programm). Eine alternative Therapie beim obstruktiven Schlafapnoesyndrom.

We investigated the therapeutic effect of marked body weight reduction on the predominantly obstructive sleep apnea syndrome by the application of an out-patient, behaviour therapy based body weight reduction program (Optifast-program) in five of our obese apnea patients (mean overweight by Broca 53.6 +/- 24.8 kg). Mean body weight reduction was 32.7 +/- 15.8 kg after six months. The mean apnea-index of 34.5 +/- 23.1/h prior to the weight reduction dropped to 7.8 +/- 6.1/h after therapy. The mean apnea-hypopnea-index (so called "respiratory disturbance index", RDI) could be reduced from 45,7 +/- 26.0/h to 14.0 +/- 11.4/h. The best therapeutic effect on the sleep related respiratory parameters was seen in patients who reached their normal weight whereas the absolute weight reduction itself seems to be less important. Our results should encourage this causal therapy in appropriate patients.

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.

Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease.

OBJECTIVE: To assess the sensitivity, specificity, and interobserver reliability of periodic sharp wave complexes in the electroencephalograms of patients with Creutzfeldt-Jakob disease. DESIGN: Sixty-eight electroencephalograms in 29 patients who had been suspected of having Creutzfeldt-Jakob disease were reanalyzed by an investigator who was unaware of the clinical data. The incidence of periodic sharp wave complexes in neuropathologically confirmed Creutzfeldt-Jakob disease vs progressive dementia other than Creutzfeldt-Jakob disease was assessed. Blinded electroencephalogram analysis was performed by a second investigator. The interobserver reliability was assessed by the kappa value. SETTING: University hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. PATIENTS: Fifteen patients with neuropathologically confirmed Creutzfeldt-Jakob disease and 14 patients who had been suspected of having Creutzfeldt-Jakob disease because of rapidly progressive dementia but in whom other dementias were diagnosed by unblinded investigators based on clinical and electroencephalographic criteria. MAIN OUTCOME MEASURE: Sensitivity and specificity of periodic sharp wave complexes assessed by their incidence in Creutzfeldt-Jakob disease vs other dementias. Interobserver reliability of periodic sharp wave complexes was expressed by the kappa value. RESULTS: For periodic sharp wave complexes, blinded electroencephalographic analysis resulted in a sensitivity and a specificity of 67% and 86%, respectively. Interobserver reliability was excellent (kappa = 0.95). CONCLUSION: This blinded electroencephalographic study in Creutzfeldt-Jakob disease confirms the high diagnostic value of electroencephalography, as previously reported by open studies.

[Functional palatoraphy and modified genioplasty in obstructive sleep apnea]. / Funktionelle Palatoraphie und modifizierte Genioplastik bei obstruktiver Schlafapnoe.

10 patients with obstructive sleep apnea syndrome (OSAS) have been treated with the new surgical procedure functional palatoraphy and modified genioplasty. 5 months after surgery 7 patients with an apnea hypopnea index under 10 were cured. Three therapy refractory patients were all overweight with a body mass index of more than 29 kg/m2. Excessively overweight patients should therefore not be operated. Following the selection criteria we introduced an effective new treatment method for OSAS.

[Treatment of obstructive sleep apnea syndrome by ambulatory, comprehensive, behavior therapy oriented weight reduction (Optifast program)]. / Die Behandlung des obstruktiven Schlafapnoesyndroms durch eine ambulante, ganzheitliche, verhaltenstherapeutisch orientierte Gewichtsreduktion (Optifast-Programm).

We investigated the therapeutic effect of marked body weight reduction on the predominantly obstructive sleep apnea syndrome by the application of an out-patient, behaviour therapy based body weight reduction program (Optifast-program) in 5 of our obese apnea patients. Mean body weight reduction was 32.7 +/- 15.8 kg after 6 months. The mean apnea-index of 34.5 +/- 23.1/h prior to the weight reduction dropped to 7.8 +/- 6.1/h after therapy. The mean apnea-hypopnea-index could be reduced from 45.7 +/- 25.9/h to 14.0 +/- 11.4/h. The best therapeutic effect on the sleep related respiratory parameters, was seen in patients who reached their normal weight. Our results shows that even severe, predominantly obstructive sleep apnea syndromes could be treated successfully with a marked body weight reduction.