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Biomedical subjects

Christoph Kellinghaus

Publications and source records attributed to Christoph Kellinghaus.

At least 19 recordsLinked to original sources

Neurophysiological abnormalities in HIV-infected long term survivors.

BACKGROUND: HIV is a neurotropic virus causing neuronal damage independent of opportunistic infections. A subgroup of patients suffer from long-term infection without developing significant disease symptoms requiring antiretroviral therapy (long-term survivors, LTS). We investigated the prevalence and severity of neurophysiological abnormalities in LTS. METHODS: The outpatient database of the Dept. of Neurology, University of Münster, was searched for HIV-infection LTS (infection for more than 9 years, no antiretroviral therapy since infection, stable CD4-positive lymphocyte count of more than 400/ul). Their neurophysiological test results (nerve conduction studies, event-related potentials, EEG) were compared to a control group of patients with similar disease duration not fulfilling the criteria for LTS. RESULTS: Sixteen LTS patients and 22 control patients were investigated. Median age at examination was 35 years. There were no significant differences between the groups regarding age, sex, duration of the disease and way of infection. By definition, CD4+-lymphocyte counts differed between LTS and both control groups. Standard nerve conduction studies of the peroneal or the sural nerve were abnormal in 1 LTS patient and 3 control patients. Sural nerve paired stimulation amplitude showed abnormal findings in 4 LTS patients and 4 control patients. P300 latency was prolonged in 4 LTS patients and 4 control patients. EEG background frequency was normal in all but one patient (LTS). There were no differences between groups regarding any of the parameters. CONCLUSION: Sensitive methods showed subtle affection of the nervous system in HIV-infected outpatients infected for more than 9 years. However, there was no difference between patients fulfilling accepted criteria of LTS, and those who did not. LTS most likely form the extreme end of a continuum of disease severity.

Adult↗

Pregabalin-associated acute psychosis and epileptiform EEG-changes.

Pregabalin is a novel anticonvulsive and analgesic drug that has been marketed in Europe for more than a year. The typical side effects are dizziness, somnolence and weight gain. We present a patient who, after unintended rapid up-titration of pregabalin, experienced psychotic symptoms associated with rhythmic EEG-changes resolving completely after discontinuation of pregabalin and benzodiazepine administration.

Acute Disease↗

Electro-clinical and imaging characteristics of focal cortical dysplasia: correlation with pathological subtypes.

INTRODUCTION: Focal cortical dysplasia (CD) is a common cause of pharmaco-resistant epilepsy. CD is due to abnormalities in neuronal migration, proliferation, and/or differentiation that result in four distinct pathological subtypes: 1A, 1B, 2A, and 2B. In order to provide clinical correlation to these pathological subtypes, we reviewed the electro-clinical and imaging characteristics and surgical outcomes of the four pathological subtypes of CD. METHODS: We retrospectively reviewed patient data from epilepsy surgeries at the Cleveland Clinic Foundation between 1990 and 2002. Only those patients with the definite pathological diagnosis of isolated cortical dysplasia were included in the study (n = 145). RESULTS: Pathological subtypes 2A and 2B were predominantly frontal in location, and had a more severe epilepsy syndrome with lower intelligence quotient scores than subtypes 1A and 1B. Patients with subtype 1A FCD had less severe, later onset epilepsy that was predominantly located in the temporal lobe. Risk factors for epilepsy included febrile seizures for type 1A, head trauma for types 1A and 1B, and perinatal adverse events for type 2B. Type 2B demonstrated significantly more FLAIR signal abnormalities than the other groups. Sixty-three percent of patients overall had an Engel I outcome at 6 months follow-up. The best outcomes were in the 2B subtype, and in those who did not require an invasive EEG evaluation. CONCLUSIONS: Clinically important differences exist between the pathological subtypes of CD, which may assist in their management, and provide further insight into their underlying pathophysiology.

Adolescent↗

The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.

Cortical dysplasia (CD) is often associated with pharmacoresistant epilepsy. Previous studies showed increased expression of the NMDA receptor subunit NR2B in dysplastic and epileptic human neocortex. We tested the hypothesis that differential increase of NR2B constitutes an epileptogenic mechanism in humans. Dysplastic neocortex and lateral temporal lobe regions resected for treatment of pharmacoresistant seizures were processed for electrophysiological, histological, and immunocytochemical studies. Assignment to the "dysplastic" (n = 8) and "non-dysplastic" (n = 8) groups was based on histology. Neurons in "dysplastic" samples differentially stained for NR2B. Western blot (n = 6) showed an immunoreactive band for NR2B in three out of four "dysplastic" samples. Epileptiform field potentials (EFP) were elicited in vitro by omission of magnesium from the bath. EFP in "dysplastic" slices were characterized by multiple afterdischarges, occurring at a significantly higher repetition rate than EFP in non-dysplastic slices. The NR2B-specific NMDA receptor inhibitor ifenprodil (10muM) suppressed EFP in dysplastic slices. In non-dysplastic slices, burst repetition rate did not change with ifenprodil application. In both dysplastic and non-dysplastic slices, EFP were suppressed by a non-specific NMDAR antagonist (APV) or AMPA receptor antagonist (CNQX). These results provide additional evidence that the differential expression of NR2B in dysplastic human neocortex may play a role in the expression of in-situ epileptogenesis in human CD. NR2B may constitute a target for new diagnostic and pharmacotherapeutic approaches.

Adolescent↗

The prognostic value of [F]FDG-PET in nonrefractory partial epilepsy.

PURPOSE: Regional abnormalities of cerebral glucose metabolism, as identified by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) have prognostic value regarding the outcome of epilepsy surgery in patients with refractory partial epilepsy. The value of FDG-PET abnormalities in nonrefractory patients has not been investigated systematically. This study examines whether FDG-PET could be used for early identification of nonrefractory epilepsy in patients who will become pharmacoresistant later during the course of their disease. METHODS: We investigated interictal abnormalities of cerebral glucose metabolism by using FDG-PET in 125 consecutive patients with nonrefractory cryptogenic partial epilepsy and normal cranial magnetic resonance imaging (MRI), and we compared relative changes in seizure frequency in 90 patients after > or =2 years of follow-up. RESULTS: Regional asymmetry of tracer distribution was seen in 43 of the 90 patients. Forty-one patients had regional glucose hypometabolism in the temporal and two patients in an extratemporal region. No difference between patients with and without a hypometabolic focus was found regarding seizure freedom after follow-up. This held true also for the subgroup of patients with epilepsy onset within 1 year before admission. Only patients with regional glucose metabolism showed an increase in seizure frequency. Multivariate analysis showed that only anticonvulsive treatment before index admission and the possibility of localizing the epileptogenic focus by using all available clinical and EEG data were independently associated with continuing seizures after a median follow-up period of 43 months. CONCLUSIONS: Regional hypometabolism in FDG-PET is not significantly associated with a lower likelihood of successful anticonvulsant drug therapy in patients with nonrefractory partial epilepsy. Careful analysis of all routinely available clinical and neurophysiologic data has a much better predictive power to identify patients with medically refractory epilepsy early in the course of the disease. However, if PET data are available, they could help in identifying patients with a less benign course.

Adolescent↗

Focal semiologic and electroencephalographic features in patients with juvenile myoclonic epilepsy.

PURPOSE: A few reports have described focal electroencephalographic or clinical features or both of juvenile myoclonic epilepsy (JME), but without video-EEG documentation. We examined focal clinical and EEG features in patients with JME who underwent video-EEG monitoring. METHODS: Twenty-six patients (nine males and 17 females) who had seizures recorded during video-EEG monitoring were included. Age at seizure onset was 0 to 22 years (mean, 12.3 years), and age at monitoring was 12 to 44 years (mean, 26.5 years). In one patient with left parietooccipital epilepsy, primary generalized tonic-clonic seizures developed after resection of the parietal tumor. Two patients had both temporal lobe epilepsy and JME. Videotaped seizures in each patient were analyzed. Interictal and ictal EEG also were analyzed for any focal features. RESULTS: Focal semiologic features were observed in 12 (46%) of 26 patients. Six patients had focal myoclonic seizures, and two had Figure 4 sign: one with version to the left, and another had left version followed by Figure 4 sign, and left arm clonic seizure. Their ictal EEGs were generalized at onset but with a lateralized evolution over the right hemisphere. The patient who had both JME and left parietooccipital epilepsy, right arm clonic seizure, and Figure 4 sign was seen during a generalized EEG seizure. Interictally, one patient had temporal sharp waves, and another had run of spikes in the right frontal region. CONCLUSIONS: Fourteen (54%) of 26 patients with JME exhibited focal semiologic or electroencephalographic features or both. Video-EEG was essential in reaching a correct diagnosis and choosing an appropriate antiepileptic drug regimen.

Adolescent↗

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↗

Lateralizing value of Todd's palsy in patients with epilepsy.

The authors retrospectively investigated the value of Todd's palsy (TP) in lateralizing the hemisphere of seizure onset in patients admitted for video-EEG monitoring in a tertiary epilepsy center. In 29 patients, a postictal hemiparesis was observed. TP always occurred contralateral to the epileptogenic hemisphere in 27 patients (93%). In the remaining two patients, the seizure onset could not be lateralized. In some patients, TP occurred after a seizure without focal motor features or secondary generalization.

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↗

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↗

Frontal lobe epilepsy.

Frontal lobe epilepsy accounts for only 10-20% of the patients in surgical series, but the incidence in non-surgical patient cohorts seems to be much higher. The typical clinical presentation of the seizures includes contralateral clonic movements, uni- or bilateral tonic motor activity as well as complex automatism. The yield of surface EEG may be limited due to the difficulty in detection of mesial or basal foci, and the patient may be misdiagnosed as having non-epileptic events. In addition, in patients with mesial frontal foci the epileptiform discharges may be mislateralized ("paradoxical lateralization"). Therefore, epilepsy surgery has been commonly considered as less promising in patients with frontal lobe epilepsy. However, the advent of sophisticated neuroimaging techniques, particularly MRI with epilepsy-specific sequences, has made it possible to delineate the epileptogenic lesion and detect a specific etiology, in an increasing number of patients. Thus, the success rate of epilepsy surgery in frontal lobe epilepsy is currently comparable to temporal lobe epilepsy, if the candidates are carefully selected. Patients with frontal lobe epilepsy who do not respond to anticonvulsive medication, and who are not eligible for epilepsy surgery may benefit from alternative approaches such as electrical brain stimulation.

Anticonvulsants↗