Gabapentin-induced severe myoclonus in a patient with impaired renal function.
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Aged↗
Biomedical subjects
Hartmut Meierkord
Publications and source records attributed to Hartmut Meierkord.
Increased extracellular K+ concentration reduces the efficacy of N-methyl-D-aspartate receptor antagonists to block spreading depression-like depolarizations and spreading ischemia.
BACKGROUND AND PURPOSE: Spreading depression (SD)-like depolarizations may augment neuronal damage in neurovascular disorders such as stroke and traumatic brain injury. Spreading ischemia (SI), a particularly malignant variant of SD-like depolarization, is characterized by inverse coupling between the spreading depolarization wave and cerebral blood flow. SI has been implicated in particular in the pathophysiology of subarachnoid hemorrhage. Under physiological conditions, SD is blocked by N-methyl-D-aspartate receptor (NMDAR) antagonists. However, because both SD-like depolarizations and SI occur in presence of an increased extracellular K+ concentration ([K+]o), we tested whether this increase in baseline [K+]o would reduce the efficacy of NMDAR antagonists. METHODS: Cranial window preparations, laser Doppler flowmetry, and K+-sensitive/reference microelectrodes were used to record SD, SD-like depolarizations, and SI in rats in vivo; microelectrodes and intrinsic optical signal measurements were used to record SD and SD-like depolarizations in human and rat brain slices. RESULTS: In vivo, the noncompetitive NMDAR antagonist dizocilpine (MK-801) blocked SD propagation under physiological conditions, but did not block SD-like depolarizations or SI under high baseline [K+]o. Similar results were found in human and rat neocortical slices with both MK-801 and the competitive NMDAR antagonist D-2-amino-5-phosphonovaleric acid. CONCLUSIONS: Our data suggest that elevated baseline [K+]o reduces the efficacy of NMDAR antagonists on SD-like depolarizations and SI. In conditions of moderate energy depletion, as in the ischemic penumbra, or after subarachnoid hemorrhage, NMDAR inhibition may not be sufficient to block these depolarizations.
2-Amino-5-phosphonovalerate↗
A "malignant" variant of status epilepticus.
BACKGROUND: Status epilepticus (SE) frequently does not respond to common first-line anticonvulsants. In a substantial portion of patients, administration of anticonvulsant anesthetics is inevitable. Even this aggressive approach fails to terminate SE in an undefined number of cases. We have coined the term malignant SE for this most severe variant of SE. OBJECTIVE: To assess frequency, risk factors, and in-hospital outcome of malignant SE. DESIGN: Retrospective cohort study. SETTING: Neurologic intensive care unit of a large university hospital. Patients Sample of 35 episodes of SE not responding to first-line anticonvulsants in 34 patients. MAIN OUTCOME MEASURES: Predictive and prognostic features of episodes of malignant SE with persistent epileptic activity after high-dose anesthetics compared with features of the remainder of cases with refractory SE and persistent epileptic activity after failure of first-line anticonvulsants. RESULTS: Status epilepticus that could not be controlled by first-line anticonvulsants resulted in malignant SE in 20% of cases. Patients with malignant SE were significantly younger than patients with refractory SE (P = .03). Encephalitis was identified as an independent risk factor for malignant SE (P = .008). Outcome in malignant SE was poor, with significantly longer duration of seizure activity (P<.001), longer stay in the neurologic intensive care unit (P<.001) and in the hospital (P = .007), and more patients with functional dependency at discharge from the hospital (P = .04). CONCLUSIONS: Malignant SE is not rare after failure of first-line anticonvulsants. The patient at risk is typically young and suffers from encephalitis. Such patients should be treated aggressively early in the course of SE to prevent malignant SE.
Adolescent↗
Erectile dysfunction with topiramate.
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Adult↗
Limbic self-sustaining status epilepticus in rats is not associated with hyperthermia.
PURPOSE: To evaluate the impact of limbic status epilepticus on temperature. METHODS: The perforant path in freely moving rats was stimulated electrically for 120 min to induce self-sustaining status epilepticus (SSSE). For 150 min after the end of stimulation, epidural temperature and electrographic and clinical seizure activity were assessed in animals with limbic and motor SSSE, as well as in animals without development of SE. RESULTS: Temperature in all animals with SSSE was elevated by 1.5+/-0.8 degrees C after the end of stimulation compared with baseline values (p<0.01). In animals with pure limbic SE, temperature decreased continuously to baseline values over the 150-min period of observation. In contrast, in animals with motor SSSE, temperature remained elevated during continuing epileptic activity and was still significantly higher 150 min after the end of stimulation compared with baseline (p<0.01). In animals that did not develop SSSE, temperature was not changed after the end of electrical stimulation and in the 150 min thereafter compared with baseline values. CONCLUSIONS: The results indicate that hyperthermia as seen in SE is the consequence of motor convulsions and not of epileptic activity itself, as seen in limbic SSSE.
Animals↗
Processes and components participating in the generation of intrinsic optical signal changes in vitro.
Imaging of intrinsic optical signals has become an important tool in the neurosciences. To better understand processes underlying changes in intrinsic optical signals, we studied electrical stimulation at varying strengths in hippocampal slices of adult Wistar rats. Following serial stimulation we observed an increase in light transmittance in all tested slices. During antidromic stimulation at minimum stimulation strength the increase in light transmittance was 75 +/- 8% (P < 0.05), and during orthodromic minimum stimulation 19.6 +/- 5.6% (P < 0.001) in the stratum pyramidale of the CA1-region. During orthodromic stimulation no significant difference between submaximum, maximum and supramaximum stimulation was found, indicating saturation. In contrast, submaximum antidromic stimulation yielded 56.2 +/- 12% (P < 0.05) of maximum stimulation strength, indicating recruitment. In a further set of experiments serial stimulation was carried out under glial blockade with fluoroacetate (FAC) or blockage of mitochondrial function. Amplitude and slope of the intrinsic optical signal significantly decreased in the presence of FAC (amplitude: 36 +/- 6%, P < 0.01; slope: 37 +/- 11% as compared with baseline conditions, P < 0.05). This suggests a glial participation in signal generation. Rotenone, an inhibitor of mitochondrial complex I, yielded decreased amplitudes of the intrinsic optical signal (27 +/- 7% after 40 min, P < 0.01). Our data indicate that the intrinsic optical signal change reflects type and strength of neuronal activation and point to glia and mitochondria as important participants in signal generation.
Action Potentials↗
Decrease in haemoglobin oxygenation during absence seizures in adult humans.
Near-infrared spectroscopy (NIRS) is a noninvasive method that allows the assessment of activation-induced cortical oxygenation changes in humans. It has been demonstrated that an increase in oxygenated and a decrease in deoxygenated haemoglobin can be expected over an area activated by functional stimulation. Likewise, an inverse oxygenation pattern has been shown to be associated with cortical deactivation. The aim of the current study was to determine the oxygenation changes that occur during absence seizures. We performed ictal NIRS simultaneously with video-EEG telemetry in three adult patients with typical absence seizures. NIRS probes were placed over the frontal cortex below the F1/F2 leads. During all absence seizures studied, pronounced changes in cerebral Hb-oxygenation were noted and there were no changes in the interval. We observed a reproducible decrease in [oxy-Hb] and an increase in [deoxy-Hb] during absence seizures indicating a reduction of cortical activity. Oxygenation changes started several seconds after the EEG-defined absence onset and outlasted the clinically defined event by 20-30 s.
Adult↗
Recurrent seizures do not cause hippocampal damage.
Neuronal consequences of recurrent single epileptic seizures have been discussed controversially for some time. Various cross-sectional magnetic resonance imaging (MRI) studies have shown a positive correlation between the severity of epilepsy and the extent of hippocampal damage. However, the open question whether recurrent epileptic seizures induce hippocampal structural pathology can be assessed only in longitudinal studies. The few recent follow-up studies have revealed conflicting results. In the current MRI study we have employed volumetry and T2 relaxometry to quantify hippocampal structural changes of patients with chronic partial epilepsies over a period of 3 years. Our main findings demonstrate that these patients who experience continuing epileptic seizures do no show any development of new pathology or any relevant deterioration of pre-existing hippocampal structural lesions. This argues against the assumption that recurrent epileptic seizures cause or increase structural hippocampal damage.
Adult↗
Furosemide terminates limbic status epilepticus in freely moving rats.
PURPOSE: To evaluate the anticonvulsant properties of furosemide and to determine sedative side effects compared with pentobarbital and diuretic side effects compared with saline-treated controls in an experimental model of limbic status epilepticus. METHODS: Self-sustaining status epilepticus was induced in rats by continuous electrical stimulation of the perforant path. Five minutes after the end of the stimulation, animals were given 100 mg/kg furosemide, 30 mg/kg pentobarbital, or an equal amount of saline, intraperitoneally. After administration of the substance, animals were monitored clinically and electrographically for 3 h regarding status epilepticus, level of sedation, and diuresis. RESULTS: In seven of 10 animals, furosemide terminated status epilepticus after 68 +/- 26 min, whereas pentobarbital was successful in all animals after 5 +/- 0.8 min. In contrast to pentobarbital, sedation did not occur with furosemide. Weight loss after furosemide was 10.2 +/- 1.7% compared with 6.5 +/- 1.1% in animals given saline (p < 0.001). CONCLUSIONS: The results suggest that furosemide may serve as an alternative or additional agent for refractory complex partial status epilepticus in patients in whom common anesthetics are not justifiable.
Animals↗
Intrinsic optical imaging reveals regionally different manifestation of spreading depression in hippocampal and entorhinal structures in vitro.
The spatiotemporal features of spreading depression (SD) were analyzed in vitro by using combined hippocampal-entorhinal cortex slices. SDs were induced by microinjection of 1 M KCl in the stratum radiatum of the CA1 region of the hippocampus. Measurements of extracellular field potentials, extracellular space (ECS) volume changes and intrinsic optical signal changes were combined to study SD features in different regions of the slice. Each SD was associated with a pronounced shrinkage of the extracellular space (ECS) volume and a decrease in light transmittance. The beginning of the optical signal change occurred simultaneously with the electrographic onset as measured with extracellular microelectrodes but outlasted the dc shift for tens of seconds. The amplitude of the intrinsic optical signal change displayed marked regional variations with greatest changes of 12% in cortical regions. The signal amplitudes were considerably lower in hippocampal regions. The analysis of spread patterns revealed two types of waves: fully propagated waves spreading from CA1 all the way to the temporal neocortex and abortive waves that ceased earlier. The spread velocities displayed pronounced regional differences with highest velocities of 5.4 +/- 0.3 mm/min in the area CA3 of the hippocampal formation and lowest velocities of 2.7 +/- 0.1 mm/min in cortical regions.
Animals↗
Seizure spread through the life cycle: optical imaging in combined brain slices from immature, adult, and senile rats in vitro.
The semiology of epileptic seizures changes during the lifetime. Hence, it can be assumed that age-related changes in brain plasticity influence the patterns of seizure onset, spread and propagation velocity. We employed the 4-aminopyridine model of epilepsy to study seizure-like events in vitro. Combined entorhinal cortex-hippocampus brain slices from juvenile (10-13 days), adult (2-3 months), and senile (24-27 months) rats were examined using electrophysiological recordings and imaging of intrinsic optical signals. In the juvenile group, seizure onset was multifocal in all slice regions including the hippocampus. Onset in adult animals was confined to the entorhinal cortex and to neocortical regions. In slices from senile animals, there was a preponderance of seizure onsets in the neocortex. Spread patterns were highly variable in the juvenile group and became gradually more monomorph with increasing age. Propagation velocities were highest in the adult group, with maximum values of 1.51 +/- 0.68 mm/s. In the juvenile group, they amounted to 0.97 +/- 0.39 mm/s, and to 1.18 +/- 0.42 mm/s in senile slices. The results of this study indicate that age-related changes in brain plasticity profoundly affect spread patterns, which may contribute to the clinically observed changes in seizure semiology during early childhood, adulthood and senescence.
Aging↗