Search PubMed⌕ Search

Biomedical subjects

H Meierkord

Publications and source records attributed to H Meierkord.

36 records · Page 2Linked to original sources
PubMed1997

'Complicated' autosomal dominant familial spastic paraplegia is genetically distinct from 'pure' forms.

BACKGROUND: The familial spastic paraplegias (FSPs) are hereditary neurodegenerative disorders with an unknown pathogenesis. Pure and complicated forms are currently differentiated on clinical grounds. To date, no linkage studies in complicated FSP have been reported, and candidate genes have not been suggested. Three different gene loci responsible for pure autosomal dominant FSP and 1 for pure autosomal recessive FSP recently have been found. This raises the question of whether the complicated forms may also be linked to any of these loci. OBJECTIVE: To investigate whether complicated autosomal dominant FSP is allelic to any of the pure forms with defined loci. DESIGN: Clinical characterization of a large kindred that included 4 generations and multipoint linkage analyses. SETTING: Universitätsklinikum Charité, Humboldt-Universität Berlin, Neurologische Klinik und Poliklinik, Berlin, Germany. PATIENTS: Twenty-six family members, 13 of whom were affected. RESULTS: Thirteen members of a large family of 4 generations experienced a slowly progressive syndrome of spastic paraplegia. Hypomimia, bradykinesia, axial and limb rigidity, supranuclear gaze palsy, dysarthria, bladder and sphincter disturbances, cerebellar signs, and epilepsy were noted as additional features in some of the affected individuals. The mean age at onset was 20 years (range, 5-30 years), and the pattern of transmission was compatible with an autosomal dominant mode of inheritance. The CAG-repeat expansions in the spinocerebellar ataxia type 1 and Machado-Joseph disease genes were not found. Linkage analysis with the use of a panel of (AC)n dinucleotide repeat markers from the Généthon map demonstrated exclusion of all 4 FSP loci recently mapped by linkage to pure forms of FSP on chromosomes 14q, 2p, 15q, and 8. CONCLUSIONS: Complicated FSP in this family is not linked to any of the known pure FSP loci, including the recessive one. Therefore, the clinical differentiation of both forms still is of major relevance.ACKG

Aged↗
PubMed1997

Structural consequences of status epilepticus demonstrated with serial magnetic resonance imaging.

OBJECTIVES: To investigate MRI changes during tonic-clonic and focal motor status epilepticus. MATERIAL AND METHODS: Serial MRI-investigations with saggital, coronal and axial spin-echo (SE) T1-weighted 500/15 (repetition time [TR] msec/echo time [TE] msec) with and without application of gadolinium-DTPA, proton-density-SE 2100/30 and SE T2-weighted 2100/90 images. Correlation with seizure frequency and general clinical state and by using constant EEG recordings as well as video-EEG monitoring. RESULTS: Initially, images were normal but several days after onset of status epilepticus focal hyperintensive signal changes on T2-weighted images consistent with focal oedema were seen. The oedema produced a local mass effect as demonstrated with angiography. These changes occurred at a time when there were massive epileptic discharges registered by EEG monitoring in both cases. On subsequent images the oedema resolved but atrophy in combination with a high signal on T2-weighted images suggestive of gliosis were noted in identical regions. In the 1st case it could not completely be ruled out that the signal changes were caused by an encephalitis. However, the signal changes occurred in close time correlation with the epileptic seizure activity rendering the assumption less likely that the signal changes were caused by the encephalitis. In the 2nd case the signal changes could not be attributed to cortical dysplasia or any other condition than the epileptic activity itself. CONCLUSION: Prolonged epileptic seizure activity may cause neuronal damage associated with a typical pattern of MRI signal changes.

Adult↗
PubMed1997

Decreased N-acetyl-aspartate/choline ratio and increased lactate in the frontal lobe of patients with Huntington's disease: a proton magnetic resonance spectroscopy study.

BACKGROUND: Both the effect of the mutation and the pathogenesis of Huntington's disease are unknown and a lack of biological markers for the natural history of the disease impedes the evaluation of novel therapeutic approaches. METHODS: Proton magnetic resonance spectroscopy was carried out on a frontal region of the cortex in 17 patients with clinically overt Huntington's disease and four asymptomatic gene carriers. RESULTS: Eight of 17 (47%) clinically affected patients with Huntington's disease and each of the asymptomatic carriers had lactate peaks in the frontal cortex which were not present in controls. The N-acetyl-aspartate/choline (NAA/Ch) ratio was significantly reduced in the symptomatic patients indicating the presence of neuronal loss. The reduction was related to the clinical severity of the disease and was absent in the asymptomatic carriers. CONCLUSION: The finding of lactate peaks supports the hypothesis that disturbed cerebral energy metabolism contributes to the pathogenesis of Huntington's disease.

Adult↗
PubMed1997

Ictal speech arrest and parasagittal lesions.

Lesions in the parasagittal region may cause seizures with speech arrest. To correlate lesion localization within the parasagittal region with ictal speech function we studied 11 patients with parasagittal lesions. The exact lesion localization was assessed with magnetic resonance imaging. In all patients with speech arrest the lesion involved the left superior frontal gyrus (n = 6), in 3 patients the lesion was confined to this gyrus. Speech arrest did not occur in patients with right-sided lesions (n = 4) or left-sided lesions outside the superior frontal gyrus (n = 1). Our data suggest that a small lesion confined to the left superior frontal gyrus (the supplementary motor area) is sufficient to cause speech arrest.

Adult↗
PubMed1996

Effects of gamma-aminobutyric acid (GABA) agonists and GABA uptake inhibitors on pharmacosensitive and pharmacoresistant epileptiform activity in vitro.

1. Lowering of the extracellular Mg(2+)-concentration induces various patterns of epileptiform activity in combined rat entorhinal cortex-hippocampal brain slices. After a prolonged period of exposure to Mg(2+)-free medium seizure-like events in the entorhinal cortex change to a state of late recurrent discharges which cannot be blocked by clinically available antiepileptic drugs. This late epileptiform activity thus represents a useful model to test the effects of new anticonvulsant substances. 2. A mechanism possibly underlying the development of sustained seizure-like activity is the loss of synaptically released gamma-aminobutyric acid (GABA). Drugs which increase the amount of GABA available in presynaptic endings might thus be useful in the treatment of these therapeutically complicated forms of epilepsy. 3. Therefore, we studied the effects of various substances increasing GABA-mediated inhibition on early and late forms of epileptiform activity. GABA and the GABAA receptor agonist muscimol blocked both the pharmacosensitive discharges in the hippocampus and entorhinal cortex as well as the late recurrent discharges in the medial entorhinal cortex. The GABAB receptor agonist baclofen blocked the recurrent short discharges very potently, but did not consistently block seizure-like events and late recurrent discharges in the entorhinal cortex. 4. GABA uptake blockers showed a differential potency to block the various discharge patterns. Whereas nipecotic acid and beta-alanine suppressed all forms of epileptiform activity albeit at high concentrations (1-5 mM), tiagabine was much more potent in blocking the hippocampal recurrent short discharges and the seizure-like events in the medial entorhinal cortex, but could not block the late recurrent discharges. 5. Our data support the idea that prolonged neuronal overactivity might result in a loss of synaptically available GABA. Selective block of uptake into glia cells or substitution of the transmitter may therefore be an efficient strategy for the treatment of severe prolonged epileptic discharges whereas block of neuronal GABA uptake fails to counteract synchronized discharges in this situation.

Animals↗
PubMed1994

Epilepsy and sleep.

This review discusses several aspects of epilepsy and sleep. The level of wakefulness is controlled by transmitters such as acetylcholine, norepinephrine, serotonin, and histamine. These neurotransmitters are involved in modulatory neurotransmission of the ascending brain stem systems, which play an important role in controlling the sleep-wake cycle. Experimental evidence suggests that rapid eye movement sleep atonia is induced by increased endogenous acetylcholine release. Regarding sleep factors, recent data suggest that prolactin may stimulate rapid eye movement sleep and that growth hormone-releasing factor is involved in non-rapid eye movement sleep regulation. The neuropharmacologic features of several animal models of epilepsy have been investigated. Epileptiform discharges of genetic absence seizures in rats have been found to be suppressed by cholinergic drugs. The beta-carboline abecarnil has a strong antiepileptic effect on spike-wave discharges in rats that generate spontaneous spike-wave discharges, and it may be useful as an antiepileptic drug. Sleep epilepsy has been studied in a model of amygdala-kindled kittens. During the postkindling development, multifocal epilepsy with convulsions occurred that were distributed throughout the sleep-wake cycle; this finding agrees with the clinical literature. A typical feature of juvenile myoclonic epilepsy is the occurrence of seizures in a strict relationship to the sleep-wake cycle. There is now some neurophysiologic evidence that this syndrome also causes disturbance of sleep stability with increased arousal reactions. Nocturnal paroxysmal dystonia is not a homogeneous entity. Several clinical reports indicate that the short-lasting variant is most likely a form of frontal lobe epilepsy, but the nature of the longer-lasting variants is still obscure.

Animals↗
PubMed1994

Plasma concentrations of prolactin, noradrenaline, vasopressin and oxytocin during and after a prolonged epileptic seizure.

The time course and extent of changes in plasma prolactin, noradrenaline, vasopressin and oxytocin levels is reported following serial observations of a prolonged epileptic seizure arising in the temporal lobe, recorded by video-EEG-telemetry, in which the epileptic activity evolved from a simple partial to complex partial to secondarily generalised attack. The prolactin levels were markedly elevated during the phase of the simple partial seizure, at a time when consciousness was preserved, when motor activity was minimal and when EEG activity was highly localised. The hormonal levels continued to rise during the subsequent seizure evolution, suggesting that the duration (or intensity) of the seizure is an important, perhaps the most important, factor determining the degree of prolactin release during limbic seizures. Indeed, the prolactin elevation in this case (26 times the baseline level) is higher than any previously recorded, reflecting the unusual duration and intensity of this seizure. We did not observe the phenomenon of "exhaustion" of prolactin release and levels peaked after 49 min, and were high for over 2 h after the onset of the seizure, and after the convulsion had ceased. The concentrations of vasopressin, oxytocin and noradrenaline remained low during the aura, but rapidly increased during the phase of generalisation. The oxytocin and noradrenaline levels peaked during the phase of generalised convulsion, but the vasopressin levels peaked well into the post ictal phase, and remained high for several hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[New knowledge of the etiology and pathogenesis of Huntington chorea].

Huntington's disease (HD) is a neurodegenerative disorder for which no causal therapy is currently available. It is inherited as an autosomal dominant trait and the responsible gene was localized 10 years ago to chromosome 4. Recently the gene has been identified. This discovery now allows a definitive diagnosis to be made in most cases. Preclinical testing, however, requires careful psychological counselling. So far the structure and function of the gene product are unknown. Using experimental neurotoxicological methods it is possible to mimic several features of the disease process to such an extent that preliminary hypotheses regarding the function of the encoded protein are possible. It will be of great interest to see how the results of molecular genetic studies and of experimental research can be synthesized in the future.

Adult↗
PubMed1992

Comparison of the effects of frontal and temporal lobe partial seizures on prolactin levels.

The acute effects of partial (focal) epileptic seizures on serum prolactin levels were studied in two groups of patients: (1) 10 with temporal lobe seizures and (2) 11 with seizures that arose from the frontal lobes, recorded on cable video-electroencephalographic telemetry. Six of the eight complex partial seizures of temporal lobe origin were associated with a marked rise in prolactin levels at 10 minutes after onset (rise in levels, from a mean of 279 to 534 mU/L), compared with a rise in only one of the eight frontal lobe complex partial seizures. None of the five simple partial seizures (two of temporal and three of frontal lobe origin) was associated with a marked rise in prolactin levels. This difference in prolactin response following complex partial seizures of frontal and temporal lobe origin may help in the clinical differentiation of these seizures. A failure of prolactin levels to rise does not, however, exclude a diagnosis of complex partial seizures; thus, this measurement will not help in the clinical differentiation of frontal lobe complex partial seizures from psychogenic attacks.

Adolescent↗
PubMed1992

Is nocturnal paroxysmal dystonia a form of frontal lobe epilepsy?

The sex ratio, age at onset, and ictal features of nine patients with nocturnal paroxysmal dystonia were compared with those of eight patients with daytime frontal lobe seizures and eight patients with nocturnal motor attacks of known epileptic origin. All patients underwent video electroencephalography telemetry. There were no clinical features that would allow distinction between the groups and no single phenomenon was uniquely seen in nocturnal paroxysmal dystonia. This study provides no evidence that nocturnal paroxysmal dystonia is a separate diagnostic entity.

Adolescent↗
PubMed1992

[Clinical and neurophysiologic markers of epilepsy with frontal lobe seizures in a series of patients diagnosed by video-EEG-telemetry].

The general and ictal clinical features, including EEG findings, of 20 consecutive patients with frontal lobe epilepsy are presented. Diagnosis in all cases was based on video-EEG telemetry using strict criteria. Among the ictal motor phenomena, turning movements, dystonic, choreic and ballistic features prevailed. Ten patients vocalised during their seizures but loss of consciousness was rare, even if there was pronounced motor involvement. The duration of attacks generally was short, not exceeding 60 seconds in 18 patients, in whom sudden onset and cessation of seizures was noted. Ten patients showed inter-ictal epileptiform EEG activity and 19 had ictal abnormalities. The short duration and ictal clinical course may be helpful in differentiating frontal seizures from pseudoseizures.

Adolescent↗
PubMed1991

The clinical features and prognosis of pseudoseizures diagnosed using video-EEG telemetry.

A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.

Adult↗
PubMedDate not supplied

Transient loss of inhibition precedes spontaneous seizures after experimental status epilepticus.

The pathophysiological mechanisms that cause spontaneous seizures following status epilepticus are largely unknown. Erosion of inhibition is regarded as an important pathophysiological hallmark of ongoing status epilepticus. Therefore, we investigated if loss of inhibitory functions also plays an important role in the development of spontaneous seizures after status epilepticus. Furthermore, we analyzed possible changes in excitation that might contribute to epileptogenesis. Finally, neuronal cell loss in the dentate gyrus granule cell layer was analyzed. In rats, inhibition and excitation in the dentate gyrus were monitored 1, 4, and 8 weeks after electrically induced self-sustaining status epilepticus (SSSE). Control animals had electrodes implanted either without subsequent stimulation or with stimulation but under barbiturate anesthesia, neither of which resulted in subsequent spontaneous seizures or impairment of inhibition. Following SSSE 80% of animals developed seizures after 8 weeks. A pronounced impairment of inhibition 1 week after SSSE was followed by gradual recovery over 8 weeks. In the dentate gyrus, cell damage was highly variable most likely explaining the heterogeneity of changes in excitatory parameters. Loss of GABAergic inhibition in the dentate gyrus may facilitate initiation of epileptogenesis but impaired inhibition is not required for the process of epileptogenesis to be maintained.

Animals↗
PubMedDate not supplied

Optical imaging reveals reduced seizure spread and propagation velocities in aged rat brain in vitro.

Old age is the most common time for patients to develop epileptic seizures, and due to their frequent unusual clinical presentation the diagnosis of epilepsy is often delayed in the elderly. It is as yet unknown if pronounced alterations in the plastic properties of aging nervous tissue contribute to these phenomena. We employed a non-lesional in vitro epilepsy model to study seizure susceptibility, spread pattern, and propagation velocities in combined hippocampal-entorhinal cortex slices of aged rats and controls using electrophysiological methods and imaging of intrinsic optical signals. In aged animals we saw a less extensive spread of seizure-like events into areas adjacent to the region of onset of activity and a decreased spread velocity in various anatomical regions. In addition, both the activity-dependent shrinkage of the extracellular space (ECS)-volume and the extracellular K(+) concentration were significantly reduced compared to controls. The results of this study are consistent with the clinical observation that epileptic seizures in the elderly have a reduced tendency to spread. In addition, our data suggest that in the absence of structural lesions seizure susceptibility in the aging brain is not increased.

Aging↗