PubMed Health⌕ Search

Biomedical subjects

Hans O Lüders

Publications and source records attributed to Hans O Lüders.

At least 19 recordsLinked to original sources

Functional connectivity in human cortical motor system: a cortico-cortical evoked potential study.

In order to understand the complex functional organization of the motor system, it is essential to know the anatomical and functional connectivity among individual motor areas. Clinically, knowledge of these cortico-cortical connections is important to understand the rapid spread of epileptic discharges through the network underlying ictal motor manifestation. In humans, however, knowledge of neuronal in vivo connectivity has been limited. We recently reported a new method, 'cortico-cortical evoked potential (CCEP)', to electrically track the cortico-cortical connections by stimulating a part of the brain through subdural electrodes and recording the cortical evoked potentials that emanate from a distant region of the cortex via neuronal projections. We applied the CCEP methodology to investigate in vivo cortico-cortical connections between the lateral motor cortex [LMCx; sensorimotor (SM) and lateral premotor areas] and the medial motor cortex [MMCx; supplementary motor area proper (SMA), pre-SMA and foot SM]. Seven patients with intractable partial epilepsy were studied. These patients had chronic implantation of subdural electrodes covering part of the lateral and medial frontal areas. As a part of the routine pre-surgical evaluation, comprehensive cortical mapping was performed by electrical stimulation of the subdural electrodes, and the precise localization of the subdural electrodes was defined by MRI co-registration. Single-pulse electrical stimuli were delivered to MMCx (7 patients) and LMCx (4), and CCEPs time-locked to the stimuli were recorded by averaging electrocorticograms from LMCx and MMCx, respectively. Short-latency CCEPs were observed when stimulating MMCx and recording from LMCx (mean latency: 21.6 ms, range: 9-47 ms) and vice versa when stimulating LMCx and recording from MMCx (mean latency: 29.4 ms, range: 11-57 ms). In terms of the location of these stimulus sites and CCEP responses along the rostrocaudal axis, regression analysis revealed a consistent correlation between the sites of stimulation and maximum CCEP for stimulation of both MMCx and LMCx. Functionally, stimulation of the positive motor areas in MMCx elicited CCEPs at the somatotopically homologous regions in LMCx (71%). The same findings were observed in MMCx (82%) upon stimulation of LMCx. In four subjects in whom bi-directional connectivity was investigated by stimulating both MMCx and LMCx, reciprocality was observed in the majority of connections (78-94%). In conclusion, the present study demonstrated a human motor cortico-cortical network connecting (i) anatomically homologous areas of LMCx and MMCx along the rostrocaudal cognitive-motor gradient; and (ii) somatotopically homologous regions in LMCx and MMCx in a reciprocal manner.

Adolescent↗

Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.

The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the alpha subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a three- to fivefold increase in Ca(2+) sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease.

Adolescent↗

Detection of epileptiform activity by human interpreters: blinded comparison between electroencephalography and magnetoencephalography.

PURPOSE: Objectively to evaluate whether independent spike detection by human interpreters is clinically valid in magnetoencephalography (MEG) and to characterize detection differences between MEG and scalp electroencephalography (EEG). METHODS: We simultaneously recorded scalp EEG and MEG data from 43 patients with intractable focal epilepsy. Raw EEG and MEG waveforms were reviewed independently by two experienced epileptologists, one for EEG and one for MEG, blinded to the other modality and to the clinical information. The number and localization of spikes detected by EEG and/or MEG were compared in relation to clinical diagnosis based on postoperative seizure freedom. RESULTS: Interictal spikes were captured in both EEG and MEG in 31, in MEG alone in eight, in EEG alone in one, and in neither modality in three patients. The number of detections ranged widely with no statistical difference between modalities. A median of 25.7% of total spikes was detectable by both modalities. Spike localization was similarly consistent with the epilepsy diagnosis in 85.2% (EEG) and 78.1% (MEG) of the patients. Inaccurate localization occurred only in those cases with very few spikes detected, especially when the detections were in one modality alone. CONCLUSIONS: Interictal epileptiform discharges are easily perceived in MEG. Independent spike identification in MEG can provide clinical results comparable, but not superior, to EEG. Many spikes were seen in only one modality or the other; therefore the use of both EEG and MEG may provide additional information.

Adolescent↗

Hemispherectomy for catastrophic epilepsy in infants.

PURPOSE: To report our experience with hemispherectomy in the treatment of catastrophic epilepsy in children younger than 2 years. METHODS: In a single-surgeon series, we performed a retrospective analysis of 18 patients with refractory epilepsy undergoing hemispherectomy (22 procedures). Three different surgical techniques were performed: anatomic hemispherectomy, functional hemispherectomy, and modified anatomic hemispherectomy. Pre- and postoperative evaluations included extensive video-EEG monitoring, magnetic resonance imaging, and positron emission tomography scanning. Seizure outcome was correlated with possible variables associated with persistent postoperative seizures. The Generalized Estimation Equation (GEE) and the Barnard's exact test were used as statistical methods. RESULTS: The follow-up was 12-74 months (mean, 34.8 months). Mean weight was 9.3 kg (6-12.3 kg). The population age was 3-22 months (mean, 11.7 months). Thirteen (66%) patients were seizure free, and four patients had >90% reduction of the seizure frequency and intensity. The overall complication rate was 16.7%. No deaths occurred. Twelve (54.5%) of 22 procedures resulted in incomplete disconnection, evidenced on postoperative images. Type of surgical procedure, diagnosis categories, persistence of insular cortex, and bilateral interictal epileptiform activity were not associated with persistent seizures after surgery. Incomplete disconnection was the only variable statistically associated with persistent seizures after surgery (p<0.05). CONCLUSIONS: Hemispherectomy for seizure control provides excellent and dramatic results with a satisfactory complication rate. Our results support the concept that early surgery should be indicated in highly selected patients with catastrophic epilepsy. Safety factors such as an expert team in the pediatric intensive care unit, neuroanesthesia, and a pediatric epilepsy surgeon familiar with the procedure are mandatory.

Cerebral Cortex↗

A semiological classification of status epilepticus.

The classification of status epilepticus (SE) has been a subject of discussion for many years, yet no satisfactory agreement has been reached. Due to their complexity, status episodes often defy classification according to the current international classification scheme. The semiological seizure classification (SSC) has been in use in several epilepsy centers for more than a decade, and has proven to be a valid approach to the classification of epileptic seizures. Based on the detailed analysis of more than 100 episodes of SE documented with video-EEG recordings, the authors now present a proposal for a semiological classification of status epilepticus (SCSE). The SCSE reflects the assumption implied by all modern definitions of SE that "there are as many types of status as there are types of seizures" and relies on the same principles as the SSC, focusing on the main clinical manifestations and the evolution of the status episode. The clinical manifestations of SE are subdivided into semiological components and classified along three axes: the type of brain function predominantly compromised by the seizure activity, the body part involved, and the evolution over time. Each axis contains several subcategories, so that many different levels of accuracy are possible. The SCSE, just like the SSC, is meant to be part of a comprehensive epilepsy classification which classifies as independent variables (epileptogenic zone, ictal semiology, etiology, related medical conditions) the main features of the patient's epilepsy, allowing for each variable maximum flexibility.

Autonomic Nervous System↗

A proposal for a five-dimensional patient-oriented epilepsy classification.

The recent proposal by the ILAE Task Force for Epilepsy Classification consists of a multi-axial syndrome-oriented approach. Epilepsy syndromes, as defined by the ILAE, group patients according to various, poorly defined parameters. The resulting syndromes have frequently no biological significance, with overlap among different syndromes and syndromes changing with age. Additionally, only a minority of patients can be classified syndromatically, and the axes of this classification system convey redundant information. We propose a five-dimensional, patient-oriented approach to classifying epilepsies. This approach shifts from the syndrome-oriented approach to a standard, neurological, methodological, patient-oriented approach, using independent criteria in each of the five dimensions. Similar to general neurology, the first step in each patient-physician encounter in epileptology is to take a history of the presenting symptoms and generate a hypothesis regarding the localization and etiology of the symptom within the nervous system. Therefore, the main dimensions of this classification consist of: 1) localization of the epileptogenic zone, 2) seizure semiology classified according to the semiological seizure classification, 3) etiology, 4) seizure frequency, and 5) related medical conditions. These dimensions characterize all of the information necessary for patient management, are independent parameters, and include more pertinent information with regards to patient management than the ILAE axes. All patients can be classified according to this five-dimensional system even at the initial patient 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 for increasing precision of the classification as additional information becomes available. This patient-oriented classification envisions an epileptic seizure as an independent symptom of a central nervous system dysfunction due to different causes, with various cortical localizations, occurring at various frequencies, and in conjunction with other diseases and clinical symptoms.

Adult↗

Effects of eyelid closure, blinks, and eye movements on the electroencephalogram.

OBJECTIVE: To characterize the effects of the eyeball and eyelid positions during eyeblinks on electroencephalographic (EEG) potentials. METHODS: Movements of the upper eyelids and eyes were measured in two healthy subjects using the magnetic search coil technique during horizontal and vertical eye rotations, eyeblinks, and lid closure. Corresponding signal changes were recorded simultaneously on the electroencephalogram (EEG). RESULTS: Spontaneous blinks produced small eye movements directed down and inward, whereas slow or forced blinks were associated with delayed upward eye rotations (i.e. Bell's phenomenon); both types of blinks caused positive EEG potentials with bifrontal distribution maximum at Fp1 and Fp2. CONCLUSIONS: In prior reports, these positive EEG artifacts have been attributed to upward eyeball rotation during blinks-Bell's phenomenon. By contrast, our findings indicate that movements of the eyelid contribute to a greater extent to these EEG potentials than do upward eyeball rotations. SIGNIFICANCE: Care is required in attributing EEG artifacts to movements of either eyeball or eyelid, since our findings suggest that they both contribute to these potentials.

Adult↗

Functional connectivity in the human language system: a cortico-cortical evoked potential study.

A better understanding of the mechanisms involved in human higher cortical functions requires a detailed knowledge of neuronal connectivity between functional cortical regions. Currently no good method for tracking in vivo neuronal connectivity exists. We investigated the inter-areal connections in vivo in the human language system using a new method, which we termed 'cortico-cortical evoked potentials' (CCEPs). Eight patients with epilepsy (age 13-42 years) underwent invasive monitoring with subdural electrodes for epilepsy surgery. Six patients had language dominance on the side of grid implantation and two had bilateral language representation by the intracarotid amobarbital test. Conventional cortical electrical stimulation was performed to identify the anterior and posterior language areas. Single pulse electrical stimuli were delivered to the anterior language (eight patients), posterior language (four patients) or face motor (two patients) area, and CCEPs were obtained by averaging electrocorticograms (ECoGs) recorded from the perisylvian and extrasylvian basal temporal language areas time-locked to the stimulus. The subjects were not asked to perform any tasks during the study. Stimulation at the anterior language area elicited CCEPs in the lateral temporo-parietal area (seven of eight patients) in the middle and posterior part of the superior temporal gyrus, the adjacent part of the middle temporal gyrus and the supramarginal gyrus. CCEPs were recorded in 3-21 electrodes per patient. CCEPs occurred at or around the particular electrodes in the posterior language area which, when stimulated, produced speech arrest. Similar early and late CCEPs were obtained from the basal temporal area by stimulating the anterior language area (three of three patients). In contrast, stimulation of the adjacent face motor area did not elicit CCEPs in language areas but rather in the postcentral gyrus. Stimulation of the posterior language area produced CCEPs in the anterior language (three of four patients) as well as in the basal temporal area (one of two patients). These CCEPs were less well defined. These findings suggest that perisylvian and extrasylvian language areas participate in the language system as components of a network by means of feed-forward and feed-back projections. Different from the classical Wernicke-Geschwind model, the present study revealed a bidirectional connection between Broca's and Wernicke's areas probably through the arcuate fasciculus and/or the cortico-subcortico-cortical pathway. CCEPs were recorded from a larger area than the posterior language area identified by electrical stimulation. This suggests the existence of a rather broad neuronal network surrounding the previously recognized core region of this area.

Adolescent↗

Non-epileptic seizures of the elderly.

OBJECTIVE: To characterize non-epileptic seizures (NES) in the elderly and compare their features with NES of a younger control group. METHODS: The database of the epilepsy monitoring unit of the Cleveland Clinic Foundation (CCF) was searched for patients aged 60 years and older having undergone long-term video-/EEG monitoring between 1994 and 2002, with the subsequent diagnosis of NES. Videotapes of all events were evaluated by independent observers. NES were classified based on the clinical manifestations recorded on video, EEG and imaging data, and compared with a control group of younger adults with NES. RESULTS: Thirty-nine elderly patients were included. Seventeen of them (44%) had NES only, six (15%) had both epilepsy and NES. The control group consisted of 20 patients, two of them had NES and epilepsy. The NES were classified as physiological in 10 elderly patients (43%) and one control patient. They included TIA, syncope, movement disorders and sleep disorders. Psychogenic NES were found in 13 elderly and 19 control patients and were associated with somatoform disorders, anxiety disorders, mood disorders and reinforced behavior pattern. Psychogenic NES consisted of predominant motor activity in 8 (61%) elderly and 13 (68%) control patients, unresponsiveness in 4 (31%) elderly and 2 (11%) control patients and subjective symptoms in 1 (8%) elderly and 4 (21%) control patients. Twelve (71%) of the patients of each group without evidence for epilepsy were on anticonvulsant drugs at the time of admission. CONCLUSION: NES are a frequent problem in elderly patients referred to a comprehensive epilepsy center. In contrast to a younger control group, physiological and psychogenic NES are equally frequent in the elderly. Loss of responsiveness was seen in only 20% of patients with psychogenic NES. Although most of the patients did not have any evidence for epilepsy, more than two thirds of these patients had been placed on anticonvulsive drugs.

Adult↗

Lateralizing signs during seizures in infants.

OBJECTIVE: To identify lateralizing features during seizures in infants and assess their reliability. METHODS: Infants were included if they had video-EEG monitoring at our institution, and were seizure-free for at least 12 months after epilepsy surgery. Lateralizing signs and seizure symptomatology were classified based on blinded video review. RESULTS: We analyzed 100 seizures from 19 infants (1 to 32, mean 13 months of age) (1 to 14 seizures per patient). Potential lateralizing signs were seen in 58 seizures from 12 infants, including unilateral clonic jerking (8 patients); forced, sustained tonic version of the eyes to one side (7 patients); predominantly unilateral infantile spasms (5 patients); unilateral tonic stiffening of an arm and leg (2 patients); nystagmus (2 patients) and postictal hemiparesis (1 patient). Except for tonic eye version, each of the signs was contralateral to the hemisphere of seizure-onset in all but one patient who had predominantly ipsilateral spasms and clonic arm activity. Tonic eye version was contralateral in 3 patients, ipsilateral in 1 patient, and toward either side in different seizures in 3 patients. CONCLUSION: Reliable lateralizing signs included focal clonic activity and predominantly unilateral spasms. Focal tonic activity, nystagmus and postictal hemiparesis were also consistently contralateral but were observed only in few patients. Tonic eye version was unreliable and could not be used to lateralize seizure onset. The sequence of eye and head version evolving to generalized tonic clonic convulsions was not seen in this age group.

Child, Preschool↗

Seizure semiology in the elderly: a video analysis.

PURPOSE: To describe the seizure semiology of patients older than 60 years and to compare it with that of a control group of younger adults matched according to the epilepsy diagnosis. METHODS: Available videotapes of all patients aged 60 years and older who underwent long-term video-EEG evaluation at the Cleveland Clinic Foundation (CCF) between January 1994 and March 2002 were analyzed by two observers blinded to the clinical data. A younger adult control group was matched according to the epilepsy diagnosis, and their seizures also were analyzed. RESULTS: Fifty-four (3.3%) of the 1,633 patients were 60 years or older at the time of admission. For 21 of them, at least one epileptic seizure was recorded. Nineteen patients had focal epilepsy (nine temporal lobe, two frontal lobe, two parietal lobe, eight nonlocalized), and two patients had generalized epilepsy. Seventy-three seizures of the elderly patients and 85 seizures of the 21 control patients were analyzed. In nine elderly patients and 14 control patients, at least one of their seizures started with an aura. Eleven elderly patients and 19 control patients lost responsiveness during their seizures. Approximately two thirds of the patients in both groups had automatisms during the seizures. Both focal and generalized motor seizures (e.g., clonic or tonic seizures) were seen less frequently in the elderly. CONCLUSIONS: Only a small percentage of the patients admitted to a tertiary epilepsy referral center for long-term video-EEG monitoring are older than 60 years. All seizure types observed in the elderly also were seen in the younger control group, and vice versa. Simple motor seizures were seen less frequently in the elderly.

Aged↗

Specific epileptic syndromes are rare even in tertiary epilepsy centers: a patient-oriented approach to epilepsy classification.

PURPOSE: To assess the practicability and reliability of a five-dimensional patient-oriented epilepsy classification and to compare it with the International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The dimensions consist of the epileptogenic zone, semiologic seizure type(s), etiology, related medical conditions, and seizure frequency. METHODS: The 185 epilepsy patients (94 adults, 91 children, aged 18 years or younger) were randomly selected from the database of a tertiary epilepsy center and the general neurological department of a metropolitan hospital (28 adults). The charts were reviewed independently by two investigators and classified according to both the ILAE and the patient-oriented classification. Interrater reliability was assessed, and a final consensus among all investigators was established. RESULTS: Only four (4%) adults and 19 (21%) children were diagnosed with a specific epilepsy syndrome of the ILAE classification. All other patients were in unspecific categories. The patient-oriented classification revealed that 64 adults and 56 children had focal epilepsy. In an additional 34 adults and 45 children, the epileptogenic zone could be localized to a certain brain region, and in 14 adults and five children, the epileptogenic zone could be lateralized. Fourteen adults and 21 children had generalized epilepsy. In 16 adults and 14 children, it remained unclear whether the epilepsy was focal or generalized. Generalized simple motor seizures were found in 66 adults and 52 children, representing the most frequent seizure type. Etiology could be determined in 40 adults and 45 children. Hippocampal sclerosis was the most frequent etiology in adults (10%), and cortical dysplasia (9%), in children. Seven adults and 31 children had at least daily seizures. Seventeen adults and 26 children had rare or no seizures at their last documented contact. The most frequent related medical conditions were psychiatric disorders and mental retardation. Interrater agreement was high (kappa values of 0.8 to 0.9) for both the patient-oriented and the ILAE classification. CONCLUSIONS: Specific epilepsy syndromes included in the current ILAE classification are rare even in a tertiary epilepsy center. Most patients are included in unspecific categories that provide only incomplete information. In contrast, all of the patients could be classified by the five-dimensional patient-oriented classification, providing all essential information for the management of the patients with a high degree of interrater reliability.

Adolescent↗

Severity of histopathologic abnormalities and in vivo epileptogenicity in the in utero radiation model of rats is dose dependent.

PURPOSE: Malformations of cortical development (MCDs) are a frequent cause of refractory epilepsy in humans. The in utero radiation model in rats shares many clinical and histopathologic characteristics with human MCDs. Previous studies reported the presence of clinical seizures in radiated rats, but also suggested a dose-dependent differential effect. METHODS: Time-pregnant Sprague-Dawley rats were irradiated on embryonic day E17 with 100 cGy (low dose), 145 cGy (medium dose), 175 cGy (high dose), or were left untreated. Their adult litters were implanted with bifrontal epidural and hippocampal depth electrodes and underwent long-term video-EEG monitoring. After 2 weeks of monitoring, the animals were killed and their brains processed for histological studies. RESULTS: Spikes were most frequently found in the rats that were subjected to low- and medium-dose radiation at E17 and were less frequently seen in the animals that were subjected to high-dose radiation. No interictal spikes were found in any of the control animals. Seizures were recorded in three of five animals of the medium-dose group. Histological studies showed a dose-dependent decrease in cortical thickness as well as an increase of cortical and hippocampal disorganization. CONCLUSIONS: In vivo epileptogenicity in radiated animals was present only in mild or moderate MCD. No in vivo epileptogenicity was seen in severe radiation-induced MCD.

Abnormalities, Radiation-Induced↗

Patients' perceptions of memory functioning before and after surgical intervention to treat medically refractory epilepsy.

PURPOSE: One risk associated with epilepsy surgery is memory loss, but perhaps more important is how patients perceive changes in their memories. This longitudinal study evaluated changes in memory self-reports and investigated how self-reports relate to changes on objective memory measures in temporal or extratemporal epilepsy patients who underwent surgery. METHODS: Objective memory (Wechsler Memory Scale-Revised) and subjective memory self-reports (Memory Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients approximately 6 months before and 6 months after surgery. A measure of depressive affect (Beck Depression Inventory-2nd Edition) was used to control variance attributable to emotional distress. RESULTS: Despite a lack of significant correlational relationships between objective and subjective memory for the entire sample, significant correlations between objective memory scores and self-reports did emerge for a subset of patients who evidenced memory decline. Differences also were found in the subjective memory ratings of temporal lobe versus extratemporal patients. Temporal lobe patients rated their memories more negatively than did extratemporal patients and were more likely to report significant improvements in their memory after surgery. CONCLUSIONS: In general, patients were not accurate when rating their memories compared to other adults. However, patients with significant declines in their memories were sensitive to actual changes in their memories over time relative to their own personal baselines.

Adolescent↗