Cognitive-behavioral screening in elderly patients with new-onset epilepsy before treatment.

OBJECTIVES: Cognitive comorbidity at epilepsy onset reflects disease severity and provides a baseline estimate of reserve capacities with regard to the effects of epilepsy and its treatment. Given the high incidence of epilepsy at an older age, this study analyzed objective and subjective cognition as well as quality of life in elderly patients with new-onset focal epilepsy before initiation of anti-epileptic treatment. MATERIALS AND METHODS: A total of 257 untreated patients (60-95 years of age) with new-onset epilepsy underwent objective assessment of executive function (EpiTrack) and performed subjective ratings of cognition (Portland Neurotoxicity Scale) and quality of life (QoL; QOLIE-31). RESULTS: According to age-corrected norms, 58% of patients (N=257) demonstrated deficits in executive function; major determinants were cerebrovascular etiology, neurological comorbidity, and higher body mass index. Subjective ratings indicated deficits in up to 27% of patients. Self-perceived deficits were associated with neurological, cardiovascular, and/or psychiatric comorbidity, whereas poorer QoL was related to neurological comorbidity and female gender. Objectively assessed executive functions correlated with subjective social functioning, energy, motor function, and vigilance. CONCLUSIONS: We found a relatively high QoL, a low rate of subjective impairment, but a high incidence of objective executive deficits in untreated elderly patients with new-onset epilepsy. Neurological status and body mass index, rather than seizure frequency or severity, were risk factors for cognitive impairment. Given the relevance of cognition in the course of epilepsy and its treatment, routine screening before treatment initiation is highly recommended.

[Epilepsy in the elderly]. / Epilepsie im Alter.

Epilepsies frequently only start in old age and given the current demographic trend the prevalence of epilepsy in the elderly population will increase. This article summarizes the most relevant aspects of diagnosis and therapy in elderly patients with epilepsy. Guidelines, systematic reviews or meta-analyses are lacking and there are only three randomized controlled trials of epilepsy in the elderly. Clinically, seizures in the elderly may be missed since warning signs (auras) and seizure evolution into generalized tonic-clonic seizures are rarer in older people. Sudden loss of consciousness occurs more frequently with increasing age and poses a challenge for the differential diagnosis. Therapy is more complex due to frequent comorbidity and multiple drug therapy necessitating a cautious approach. Therapy is hampered by side effects and drug interactions making a definite diagnosis indispensable and requiring the use of newer generation antiepileptic drugs. In case of doubt, to ensure a safe diagnosis long-term video EEG should be considered even in the elderly before hazarding the negative consequences of a misdiagnosis for years.

[Epileptic seizures in the elderly]. / Epileptische Anfälle im Alter.

Given current demographic trends, the prevalence of epilepsy in the elderly population will increase. This review summarizes the most relevant clinical and therapeutic findings in elderly patients with epilepsy. Guidelines, systematic reviews, and meta-analysis are lacking, and there are only three randomized controlled trials of epilepsy in the elderly. Clinically, seizures in the elderly may be overlooked since warning signs (auras) and seizure evolution into generalized tonic-clonic seizures are rarer in old people. Sudden loss of consciousness occurs more frequently with increasing age, challenging differential diagnosis. Therapy is more complex due to frequent comorbidities and multiple drug therapies, requiring a cautious approach. Especially drug interactions need to be considered. Epileptic seizures seem to be better controlled by drugs in the elderly than in young people. Therapy is hampered by side effects and drug interactions, making definite diagnosis indispensable and bringing on the need for newer-generation antiepileptic drugs.

Analysis and correction of ballistocardiogram contamination of EEG recordings in MR.

PURPOSE: To examine the influence of cardiac activity-related head movements and varying blood pulse frequencies on the shape of electroencephalography (EEG) recordings in a high magnetic field, and to implement a post-processing technique to eliminate cardiac activity-related artifacts. MATERIAL AND METHODS: Respiratory thoracic movements, changes of blood pulse frequency and passive head movements of 20 healthy subjects were examined outside and inside an MR magnet at rest in a simultaneously recorded 21-channel surface EEG. An electrocardiogram (ECG) was recorded simultaneously. On the basis of the correlation of the left ventricular ejection time (LVET) with the heart-rate, a post-processing heart-rate dependent subtraction of the cardiac activity-related artifacts of the EEG was developed. The quality of the post-processed EEG was tested by detecting alpha-activity in the pre- and post-processed EEGs. RESULTS: Inside the magnet, passive head motion but not respiratory thoracic movements resulted in EEG artifacts that correlated strongly with cardiac activity-related artifacts of the EEG. The blood pulse frequency influenced the appearance of the cardiac activity-related artifacts of the EEG. The removal of the cardiac activity-related artifacts of the EEG by the implemented post-processing algorithm resulted in an EEG of diagnostic quality with detected alpha-activity. CONCLUSION: When recording an EEG in MR environment, heart rate-dependent subtraction of EEG artifacts caused by ballistocardiogram contamination is essential to obtain EEG recordings of diagnostic quality and reliability.

[Neurolisteriosis with acute myelitis]. / Akute Myelitis bei Neurolisteriose.

Listeriosis is a bacterial infection with Listeria monocytogenes mostly affecting immunocompromised patients. In every fourth case, the CNS is involved, usually as meningoencephalitis. This case report of an immunocompetent woman represents the first one of neurolisteriosis initially presenting as cervical myelitis and progressing to supratentorial areas of the brain. Diagnosis was based on universal polymerase chain reaction from a cortical brain biopsy, followed by sequencing of the amplified rDNA gene. Under antibiotic treatment with gentamycin and ampicillin, the patient slowly recovered and has been improving ever since.

Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training.

Recovery of motor function elicited by motor training after cortical lesions in rats is enhanced by norepinephrine (neurotransmitter mediating alpha(1)-adrenergic function) and downregulated by alpha(1)-adrenergic antagonists. In spite of this, alpha(1)-adrenergic antagonists are used to treat elderly patients with hypertension and prostate hyperplasia in stroke settings. The purpose of this study was to determine the effects of a single oral dose of the alpha(1)-adrenergic antagonist prazosin on training-dependent plasticity in intact humans, a function thought to contribute to recovery of motor function after cortical lesions. We report that prazosin decreased the ability of motor training to elicit training-dependent plasticity relative to a drug-free condition. These data suggest caution when using alpha(1)-adrenergic blockers in rehabilitative clinical settings following brain lesions.

Electroencephalography during functional echo-planar imaging: detection of epileptic spikes using post-processing methods.

EEG has been used to trigger functional MRI of patients with focal epilepsy, but EEG can be obscured by artifacts during MR data acquisition, and no continuous correlation of EEG and MRI has been possible without limiting the image time. Artifacts caused by an MRI sequence were investigated in five healthy subjects, and an EEG of five patients with epileptic discharges was recorded during echo-planar imaging. All interfering frequencies in the EEG were discrete and defined by loop structures in the MRI sequence. In post-processing of the EEG interfering frequencies were automatically detected by comparing the frequency spectra of the EEG recorded before and during imaging. After elimination of interfering frequencies by filters in the time domain or by Fourier transform, reliable spike detection in the EEG recorded during MR data acquisition became feasible, without loss of EEG quality.

Tonic seizures: their significance for lateralization and frequency in different focal epileptic syndromes.

PURPOSE: To determine whether the clinical features of tonic seizures (TSZ) are useful for lateralization of epileptic syndromes and the differential diagnosis of focal epileptic syndromes. METHODS: From a group of 481 patients, 123 patients with TSZ (44 females; mean age, 22.9 years; mean age at onset, 7 years; mean duration of epilepsy, 16 years) were selected. A total of 1595 epileptic seizures, documented during videoelectroencephalographic monitoring, were analyzed. Patients who had had surgery for epilepsy previously were excluded. Seizures were classified using a semiological seizure classification. Epilepsy syndromes were classified using all test data (electroencephalography, magnetic resonance imaging, computed tomography, positron emission tomography, and single-photon emission tomography). Data were compared using chi2 analysis or the Fisher exact test. RESULTS: More patients with TSZ had extratemporal than temporal lobe epilepsies (79% vs. 1.7%; p < 0.0001) among those with an epilepsy localized to one lobe (n = 306). In the 123 patients, TSZ were part of 170 different seizure evolutions. Seizure evolutions began with TSZ as the first seizure type more often in patients with frontal lobe epilepsy (FLE) compared with patients with parieto-occipital lobe epilepsy (POLE) (40% in POLE vs. 67% in FLE; p < 0.05). In contrast, TSZ in POLE were more likely to be preceded by auras (50% in POLE vs. 26% in FLE; p < 0.05). TSZ were bilateral in 129 (76%) and unilateral in 41 (24%) seizure evolutions. Unilateral TSZ correctly lateralized the epilepsy syndrome to the contralateral hemisphere. CONCLUSION: Analysis of seizure semiology and evolution in patients with TSZ is helpful for differentiating between focal epilepsies of temporal, frontal, and parieto-occipital origin. Unilateral TSZ provide useful information for the lateralization of the epileptic syndrome.

Ictal SPECT hyperperfusion reflects the activation of the symptomatogenic cortex in spontaneous and electrically-induced non-habitual focal epileptic seizures: correlation with subdural EEG recordings.

We report a patient with left temporal lobe epilepsy and a left parietal angioma, in whom ictal SPECT showed hyperperfusion in a spontaneous and an electrically-induced, non-habitual focal seizure. A SPECT investigation during an habitual seizure originating in the left temporal lobe showed a left temporal hyperperfusion. Electrical stimulation of the parietal cortex adjacent to the location of a previously resected angioma using subdural electrodes resulted in a non-habitual seizure beginning with a unilateral somatosensory aura. Ictal SPECT of this seizure demonstrated contralateral central hyperperfusion. We conclude from our findings that ictal SPECT hyperperfusion reflects the activation of symptomatogenic cortex, which can be induced by both epileptic discharge and electrical stimulation.

Motor cortex excitability in patients with focal epilepsy.

We studied the excitability of the motor cortex using, transcranial magnetic stimulation (TMS) in patients with temporal and extratemporal epilepsy. We applied single and paired-pulse TMS to 15 patients with temporal (n = 7), extratemporal (n = 6) and focal epilepsy lateralised to one hemisphere (n = 2). Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4 h prior to testing. We determined the threshold for EMG responses at rest (RMT), the cortically evoked silent period (CSSP) and intracortical inhibition (ICI, intervals of 2-4 ms) and facilitation (ICF, 7-15 ms) and compared the results to those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres (P < 0.01. ANOVA) compared to the controls. In the hemisphere of seizure origin ('abnormal') there was a reduction of ICF (P < 0.01) and normal ICI, in the 'normal' hemisphere there was a reduced ICI (P < 0.01) and a slight reduction of ICF (P < 0.05). ICF on the 'abnormal' side was reduced (P < 0.05) compared to the 'normal' hemisphere. RMT was increased in two patients, but group comparison of RMT and CSSP showed no significant differences between patients and controls. The results suggest a remote effect of epileptic activity onto the motor cortex leading to an alteration of activity in local inhibitory circuits.

Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia.

PURPOSE: Comparison of regional reduction of GABA receptor binding and seizure onset zone in patients with extratemporal epilepsy due to focal cortical dysplasia. METHODS: Two patients with frontal lobe epilepsy who remained seizure free after partial frontal lobe resection were investigated with magnetic resonance imaging, positron emission tomography (PET) with 18F-fluoro-deoxy-glucose (FDG) and 11C-flumazenil, subdural EEG-video recordings, and postoperative benzodiazepine (BDZ)-receptor autoradiography. RESULTS: The area of reduced BDZ-receptor binding as documented by preoperative flumazenil-PET and postoperative BDZ-receptor autoradiography corresponded to the seizure onset zone and was smaller than the interictal hypometabolism documented by FDG-PET. CONCLUSION: Flumazenil-PET is a useful tool for localization of the epileptogenic zone in patients with extratemporal epilepsy caused by focal cortical dysplasia. Neuronal distribution of BDZ-receptor density confirms in vivo flumazenil-PET findings. The regional reduction of BDZ-receptor binding in focal cortical dysplasia seems to be confined to the seizure onset zone and not to the extent of dysplastic cortex.

Motor cortex excitability in patients with migraine with aura and hemiplegic migraine.

We studied the excitability of the motor cortex using transcranial magnetic stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration of the cortical and peripheral silent period and intracortical inhibition and facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with patients free of attacks for at least 48 h. In contrast to previous reports we could not find any significant differences between patient groups and compared to controls (n=17) in the parameters tested. The results suggest that there are no interictal changes of excitability of the motor cortex in migraine. This study does not support the concept of general cortical hyperexcitability in migraine secondary to a genetic predisposition or a structural alteration of inhibitory interneurones in the cortex due to repeated parenchymal insults during attacks.

Electromyography in MRI--first recordings of peripheral nerve activation caused by fast magnetic field gradients.

Prior studies on the evaluation of stimulation by MRI were based on the subjective feeling of the volunteers. A wide variety of stimulation thresholds between the subjects was observed. In order to exclude subjective perception levels as a cause of this variation, we developed a method to investigate the activation of peripheral nerves after gradient switching by electromyography (EMG) within the MR-imager. Five healthy volunteers were positioned in the MR-scanner with the bridge of the nose at isocenter. The amplitude of sinusoidal pulse trains of the anterior-posterior gradient (rise-times: 200 or 300 micros, various numbers of oscillations) was increased stepwise. Four surface electrodes were placed on the region where a muscle-twitch was reported. Electric activity of the muscle during stimulation experiments was recorded with an MR-compatible electro-physiologic amplifier. Stimulation thresholds were defined by the appearance of an EMG-signal. Thresholds were sharp and consistent with the report of the subjects.

Organization of cortical activities related to movement in humans.

The extent and function of synchronization of oscillatory elements in the human sensorimotor cortex during movement remains unclear. Here we determine whether synchronization is distributed in both the spatial and frequency domains and whether it changes according to task. Electrocorticographic (ECoG) signals were recorded from presumed nonpathological areas simultaneously with electromyographic (EMG) signals from upper limb muscles during isometric and phasic movement tasks in humans with subdural electrodes in situ for investigation of epilepsy. Functional mapping of the sensorimotor cortex was performed by previous electrical stimulation through the same ECoG electrodes used for recording. Significant coherence between ECoG and EMG was seen at discrete frequencies in the range of 7-100 Hz. There was no predilection for coherence within a given frequency band to be associated with cortical sites that had been functionally defined as producing contralateral arm motor responses on stimulation. However, coherence with muscle in the 7-14 and 15-30 Hz band tended to be associated with ECoG sites that lay close to or within the central sulcus as determined intraoperatively. The spatial pattern and frequency of coherence changed with different tasks, although similarities in the coherence pattern remained for tasks that shared common features. These findings provide support for the hypothesis that that synchronization at specific frequencies links cortical activities into a functional ensemble during voluntary movement.

Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans.

1. Blockade of uptake carriers of gamma-aminobutyric acid (GABA) has been shown to modulate inhibition in cortical slices of experimental animals, although little is known about this mechanism in vivo and, in particular, in humans. 2. The effects of blockade of GABA uptake were studied using transcranial magnetic stimulation (TMS) in humans. In eight healthy volunteers several measures of cortical excitation and inhibition were obtained before and approximately 2 h after ingestion of 5-15 mg of tiagabine (TGB). 3. After TGB ingestion, the duration of the TMS-induced silent period observable in the electromyogram of the voluntarily contracted target muscle was prolonged. Similarly, paired-pulse inhibition of the motor-evoked potential (MEP), as tested by delivering two magnetic shocks of equal suprathreshold intensities at 160 ms interstimulus interval (ISI), was more pronounced. In apparent contradistinction, paired-pulse inhibition of the MEPs produced by a subthreshold conditioning stimulus delivered 3 ms prior to a suprathreshold stimulus was reduced. Paired-pulse facilitation elicited by the same double-shock protocol at an ISI of 10 ms was increased. 4. The prolongation of the GABAB receptor-mediated component of the inhibitory postsynaptic potential observed with TGB in in vitro studies probably underlies the increase in cortical silent period duration. The reduction of the paired-pulse inhibition at 3 ms, in turn, probably reflects inhibition of GABAA receptor-mediated inhibition via presynaptic GABAB receptors. 5. These data provide in vivo evidence of differential modulation of cortical inhibition by blockade of GABA uptake. Presynaptic GABA autoreceptors may be involved in modulating cortical inhibition in the human motor cortex.

[Noninvasive protocol for surgical treatment of focal epilepsies]. / Nichtinvasives Protokoll für die epilepsiechirurgische Behandlung fokaler Epilepsien.

We present a non-invasive epilepsy surgery protocol, which includes EEG-video-monitoring, magnetic resonance imaging (MRI), interictal positron emission tomography (PET) and ictal single photon emission computerized tomography (SPECT). According to this non-invasive protocol 50 of 173 patients with medically intractable focal epilepsy underwent resective surgery. The localization of the epileptogenic zone was based on the congruence of the localizing results of EEG-video-monitoring, MRI, interictal PET and ictal SPECT. 46 (92%) of the patients had temporal and 4 (8%) had extratemporal epilepsies. 78% (n = 39) of all patients operated according to our non-invasive protocol were postoperatively completely or almost seizure free. Extramesiotemporal resections could be carried out without invasive EEG-recording if the epileptogenic zone was not adjacent to the eloquent cortex. We conclude from our results that in a considerable number of patients with medically intractable particularly temporal focal epilepsies, resective epilepsy surgery can be based on non-invasive EEG-evaluations and the risk of invasive recordings can be avoided.

Multimodal output mapping of human central motor representation on different spatial scales.

1. Non-invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS-derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2. The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3-D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS-derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3. Mean TMS-derived COG projections were located on the posterior lip of the precentral gyrus and TMS-derived COG projections were in close proximity to the mean PET-derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4. Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two-thirds of the maximum motor-evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting alpha-motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5. Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi- or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non-dominant hemisphere.

Effects of the serotonin1B/1D receptor agonist zolmitriptan on motor cortical excitability in humans.

Oral administration of zolmitriptan, a novel 5-hydroxytriptamine receptor agonist, to eight healthy volunteers significantly reduced motor cortical excitability as tested by paired transcranial magnetic stimulation (TMS) at short interstimulus intervals. Zolmitriptan did not change motor thresholds to TMS or electromyographic silent period durations. We conclude that zolmitriptan acts centrally by reducing the inhibition within the motor cortex. The results suggest that the action of zolmitriptan on motor cortical excitability does not result from changes at the level of the cell membrane but from the influence on GABAergic inhibitory interneurons.

Ictal technetium-99m ethyl cysteinate dimer single-photon emission tomographic findings and propagation of epileptic seizure activity in patients with extratemporal epilepsies.

Although ictal single-photon emission tomography (SPET) with technetium-99m ethyl cysteinate dimer (ECD) has a well-established role in the diagnostic evaluation of patients with temporal lobe epilepsy who are being considered for epilepsy surgery, its use in cases of extratemporal epilepsy is still limited. We investigated the influence of the propagation of extratemporal epileptic seizure activity on the regional increase in cerebral blood flow, which is usually associated with epileptic seizure activity. Forty-two consecutive patients with extratemporal epilepsies were prospectively evaluated. All patients underwent ictal SPET studies with simultaneous electroencephalography (EEG) and video recordings of habitual seizures and imaging studies including cranial magnetic resonance imaging and positron emission tomography with 2-[18F]-fluoro-2 deoxy-d-glucose. Propagation of epilptic seizure activity (PESA) was defined as the absence of hyperperfusion on ictal ECD SPET in the lobe of seizure onset, but its presence in another ipsilateral or contralateral lobe. Observers analysing the SPET images were not informed of the other results. PESA was observed in 8 of the 42 patients (19%) and was ipsilateral to the seizure onset in five (63%) of these eight patients. The time between clinical seizure onset and injection of the ECD tracer ranged from 14 to 61 s (mean 34 s). Seven patients (88%) with PESA had parieto-occipital epilepsy and one patient had a frontal epilepsy. PESA was statistically more frequent in patients with parieto-occipital lobe epilepsies (58%) than in the remaining extratemporal epilepsy syndromes (3%) (P<0.0002). These findings indicate that ictal SPET studies require simultaneous EEG-video recordings in patients with extratemporal epilepsies. PESA should be considered when interpreting ictal SPET studies in these patients. Patients with PESA are more likely to have parieto-occipital lobe epilepsy than seizure onset in other extratemporal regions.