Hemorheological disturbances in patients with chronic cerebrovascular diseases.

Hemorheological disturbances may occur in more than 40% of patients with ischemic cerebrovascular diseases. In this study the changes of rheological factors--hematocrit, plasma fibrinogen concentration, whole blood and plasma viscosity, red blood cell aggregation and deformability were investigated in 297 patients (173 males, 124 females, mean age 60 +/- 11 years) with transient ischemic attack or chronic phase (> 3 months after onset) ischemic stroke, and in 73 healthy volunteers (35 males, 38 females, mean age 38 +/- 7 years). Hematocrit, plasma and whole blood viscosity were significantly (p < 0.0001) elevated in cerebrovascular patients compared to controls. Plasma fibrinogen concentration (p < 0.001), red blood cell aggregation (p < 0.05) and deformability (p < 0.01) were also impaired in stroke patients. Hemorheological disturbances were dominant in stroke patients with diabetes, hyperlipidemia and smoking habits. Hematocrit, plasma viscosity and red blood cell aggregation showed a significant (p < 0.025-0.001) correlation with the severity of carotid artery stenosis. We could not find any characteristic distribution of rheological parameters among the three subtypes of brain ischemia. Our results show that all of the measured rheological parameters are significantly impaired in chronic ischemic cerebrovascular disorders, especially in diabetic, smoking and alcoholic patients. They correlate with the severity of the carotid artery stenosis, but there is no association with the type of ischemic stroke.

[Kennedy disease in a patient with progressive speech disorder]. / Kennedy-betegség egy progresszív beszédzavarban szenvedó férfiben.

Kennedy disease is an adult onset neuromuscular disease characterized by slowly progressive proximal and bulbar muscle weakness. The disease associates with gynecomastia, adult onset infertility and sensory neuropathy, and caused by pathologic expansion of CAG repeats at the N-terminal region of the androgen-receptor gene at Xq11-q12. We report on a patient presenting with slowly progressive muscle weakness of the lower extremities, progressive dysartry and swallowing difficulties. The clinical symptoms were not fully specific for the disease. Moreover the family history was suggestive for an autosomal dominant trait meaning a diagnostic pitfall at the original examination. Finally the firm diagnosis of the Kennedy disease was established by a polimerase chain reaction based method.

Headache in intracranial tumors.

The clinical data of 279 consecutive patients with brain tumors were analyzed pre- and postoperatively in the period of 1994-95. No headache had been recorded in the history of 115 patients, neither pre- nor postoperatively. Only in 139 of the remaining 164 headache patients was there a probable connection between headache and intracranial neoplasm. In the headache group the most frequent findings were metastatic brain tumors and different astrocytomas. Hypophysis adenomas and glioblastoma multiforme were frequent in the no-headache group. Progressive headache was found in 110 patients (67% of the headache group). The progressive character of the headache showed a close relationship with the prevailing edema, but not with the size of the tumor. Infratentorial and intraventricular tumors were more frequently accompanied by headache than those located supratentorially, probably due to the disturbance of CSF circulation and midline dislocation with increased intracranial pressure. Only in one-third of the patients did the site of the tumor coincide with the lateralization of headache. In half of the headache patients, pain was the first complaint. Headaches caused by tumor were characterized by pain lasting for hours, developing for weeks or months. The headache was never permanent and there was no regular daily recurrence.

Exercise-induced slow waves in the EEG of cats.

The aim of the present study was to investigate the early signs of fatigue. Cats were chronically implanted with electrodes in the frontal and occipital cortical areas, and a thermocouple was inserted into the nasal orifice to record respiratory rate. After a recovery of 10 days, the animals were trained for running on treadmill. On the day before recording, a catheter was tied into one of the common carotid arteries to record arterial blood pressure. The electroencephalogram (EEG), arterial blood pressure, and respiration were recorded continuously. At the time of deceleration of running high amplitude, slow waves appeared both in the sensorimotor and occipital cortical regions. The power spectra showed a significant increase in frequencies of 1-6 Hz in the sensorimotor cortex, and of 1-10 Hz in the occipital cortex, with a great increase in the total power. During rest the pre-running, brain activity reappeared gradually. The arterial blood pressure, the heart rate, and the respiratory rate were elevated during running, but no special changes occurred at the onset of the slow waves in the EEG. The blood glucose level was somewhat higher after the first 2-min running than the pre-running level. It is concluded that the appearance of slow waves in the EEG is an early manifestation of fatigue. The cardiorespiratory changes and the blood sugar concentrations play no role in the slowing of the electrocorticogram. The present results show the involvement of brain mechanisms in the onset of tiredness.

MK-801-induced neuronal damage in rats.

The non-competitive N-methyl-D-aspartate antagonist MK-801 has been frequently used to attenuate neurotoxicity mediated by excessive release of glutamate. However, doses of MK-801, effective to prevent cell loss in some areas have been reported to induce pathological changes in retrosplenial cortex [32]. In the present study, we examined the extent of the MK-801-induced damage. Silver staining techniques were used to label damaged neurons, axon terminals and activated microglia. In addition to the retrosplenial cortex, we observed silver-impregnated neurons in the pyriform, and entorhinal cortices, in amygdala in tenia tecti, and in the temporal two thirds of the dentate gyrus. With the exception of the dentate gyrus, signs of early degeneration appeared in the first 4 days in all observed regions. Activated microglia have been found 1 and 3 weeks after the lesion in the same areas. The time course and dose dependence of the damage was also investigated. The distribution of labeled neurons resembled the pattern observed after certain epileptic states. Our data suggest that irreversible cell damage occurred in the affected regions. These findings confirm and extend previous suggestions that, besides its protective effect, MK-801 may lead to neuronal degeneration.

A current-source density analysis of the long-term potentiation in the hippocampus.

Tetanic stimulation of presynaptic fibres induces long-term potentiation (LTP) which means enhancement of synaptic efficacy in the stimulated pathway for hours or days. In addition to that component, a permanent change occurs in the postsynaptic cells promoting their discharges. This latter effect called 'EPSP-to-spike (E-S) potentiation' is thought to be mediated by voltage-sensitive channels in the dendrites. Current-source density (CSD) analysis was made in the CA1 area of hippocampal slice preparations to find if LTP causes changes of the transmembrane currents in the stratum radiatum which can be detected with this technique. Some increase of currents associated with synaptic transmission itself at distant dendritic areas was accompanied by a disproportional enhancement of other currents attributed to activation of dendritic membranes at approximately 150 microns away from the pyramidal layer. When this current grew sufficiently large, it propagated towards the cell body layer. In slices where LTP had less E-S potentiation component, the increase in CSD at distant and more proximal portions of the dendrites remained proportional. Paired pulse facilitation induced in the same slices did not produce disproportional enhancement of proximal dendritic currents either. Our findings support the assumptions that during LTP associated with E-S potentiation the probability of activation of voltage-sensitive channel is enhanced on the dendrites of CA1 pyramidal cells.

Intracellular recordings with patch-clamp pipettes from neurons; technical problems in analysis of conductance changes during brief oxygen deprivation of hippocampal slices.

Brief oxygen deprivation causes reversible, rapid and large scale redistribution of ions in hippocampal slice preparations. Intracellular recordings revealed remarkable increases of membrane conductance in neurons restricted for the period of hypoxic spreading depression (SD). Voltage-clamp technique was applied to explore further details of the SD-associated conductance changes. Patch-clamp recording in whole-cell configuration allowed better control of membrane potentials. High resolution current-voltage (I-V) plots were obtained by ramp command technique. Limitations of the techniques and various test protocols are evaluated.

Time course of changes in long-term potentiation of synaptic transmission following subcortical deafferentation on the rat hippocampus.

Brief tetanic stimulation potentiates synaptic transmission both in the CA1 and dentate area of slices cut from normal rats. This long-term potentiation (LTP) was assayed in slices made at various times from rats subjected to complete bilateral sectioning of all subcortical afferents which enter the hippocampus. Over about one week survival time, LTP is present in the CA1 region of all and also in the fascia dentata of about 50% of slices. We found no signs of LTP in the dentate area of slices cut over 8 weeks after deafferentation, while the responses were clearly potentiated in the CA1 area of the same slices. Four week was the longest period when a somewhat modified version of LTP could be produced in the subcortically deafferented dentate area. The results confirm previous reports that subcortical afferents mediate some unknown factors essential for maintenance of long-term plasticity of intrinsic synapses in the fascia dentata. This unidentified, perhaps trophic influence diminishes in about 4 weeks after severing the subcortical fibers. In contrast, maintenance of subcortical inputs are apparently not required for the LTP in the intrinsic CA1 synapses.

An intracellular investigation into the postsynaptic responses of the principal cells in slice preparations from rat hippocampal formation.

Presumed principal cells of the hippocampus CA1 area and the gyrus dentatus were analysed intracellularly in slices cut from young rats. Membrane and postsynaptic potential properties of a sample of neurons were measured. Individual differences between prepotential and afterpotential components of various cells are emphasized. The results are in accord with findings reported by others but some further details are also provided.

Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis.

The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

Long-term potentiation in slices from subcortically deafferented hippocampi.

Long-term potentiation (LTP) can be initiated in CA1, but not in the dentate, region of slices from rats with bilateral subcortical deafferentation at 8 week survival time. At about one week survival time, LTP is present in the CA1 region of all and also in the dentate of about 50% of slices. The results suggest that subcortical cholinergic and catecholaminergic inputs are not required for the LTP in the CA1 area of the rat hippocampus.

Sudden cortical blindness following transient enhancement of steroids administered in congenital adrenal hyperplasia (case report).

A case of cortical blindness developed in an infant who suffered from congenital adrenal hyperplasia and was hospitalized for enteritis is reported. The severe but transient hypertension recorded raises the possibility that the increased doses of steroid administered may have contributed to the pathogenesis of visual impairment.

Somatosensory evoked potentials elicited by stimulation of the posterior tibial nerve in patients with multiple sclerosis.

Normal control somatosensory evoked potential data (elicited by stimulation of the posterior tibial nerve), of 20 healthy subjects were compared to the electrophysiological data of 20 patients with the diagnosis of definite or probable multiple sclerosis. The demyelinating process affects all segments of the response, causing increase in latency and decrease in amplitudes as well as lack of the potentials during the disease. Based on the literature, the neurological localization values of TPSEP are summarized. Due to its outstanding sensitivity in these cases, the procedure as advised by the authors should be used in demyelinating processes and in other spinal cord disease of different aetiology.

[Value of the carotid compression test for the diagnosis of cerebrovascular disorders]. / Der Wert des Karotis-Kompressions-Tests für die Diagnose zerebraler Durchblutungsstörungen.

The carotid compression tests have been performed in 1940 outpatients and 233 hospitalized patients with clinical signs and symptoms of cerebrovascular disturbances. The frequency of EEG slowing, positivity of the compression tests and carotis sinus hypersensitivity was in patients with local neurological signs: 36%, 22.5%, and 24.8%, while the corresponding numbers for patients without neurological signs were: 24.6%, 21.8%, 14.7%. On the basis of the carotis angiography the following groups of the patients could be formed: Thrombosis of the internal carotid artery (A), thrombosis of the anterior or medial cerebral artery (B), carotis stenosis (C), other vascular pathological signs of the arteries (D), normal angiography (E). They were compared with the control group of patients with vertebrobasilar insufficiency (F). The frequency of EEG slowing (A = 92%, B = 72%, C = 58.9%, D = 57%, E = 40%, F = 22.5%). The percentage of the positivity of carotid compression tests (A = 54%, B = 32%, C = 46%, D = 26%, E = 12%) and occurrence of carotis sinus hypersensitivity (A = 26.8%, B = 16%, C = 17.7%, D = 10.8%, E = 11.3%, F = 6.9%) were proportionate to the pathological morphological signs. The results of the compression tests may give indication for detailed clinical investigation, and are helpful in the estimation of the functional capacity of the carotid arteries in the cerebral circulation.

Cellular activity of intracerebrally transplanted fetal hippocampus during behavior.

Hippocampal tissue derived from 12-, 20-, 25- and 34-mm rat fetuses was placed in a cavity formed by unilateral aspiration of the fimbria-fornix and the overlying neocortical tissue in adult rats. From 4 to 6 months after transplantation the rats were equipped with chronic recording and stimulating electrodes. Single cell activity of the transplant was monitored during running in a wheel, drinking, and sleeping. Both complex-spike cells (n = 151) and single-spike cells (n = 80) were recorded from the graft. A portion of the neurons changed their firing rates and discharge patterns as a function of ongoing behavior. About half of the single-spike cells increased their firing frequency during running. Fifteen per cent of the single-spike cells fired rhythmically at about 8 Hz during running, and the paradoxical phase of sleep and the discharge pattern correlated with rhythmic slow activity (theta) recorded concurrently from the contralateral (intact) hippocampus. These patterns were most frequently obtained from grafts of 20- and 25-mm (16 to 18 embryonic days) fetuses. Graft neurons could be activated by stimulating the ipsilateral hippocampus or the ipsilateral perforant path, with latencies of 8-30 ms. The most common electrical pattern in grafts of all groups was the synchronous bursts of several neighboring cells and concurrent electroencephalogram sharp-waves. Sharp-waves occurred during all behaviors. Large amplitude, high-frequency electroencephalogram spindles (14-18 Hz and 30-50 Hz) and associated neuronal bursts were recorded in grafts of 12-, 20-, and 25-mm fetuses. Based on these findings we suggest that both subcortical afferents and host hippocampal afferents send axons to hippocampal grafts and form viable synaptic connections with a portion of the neurons in the graft. The frequently encountered population bursts are explained by assuming that excitatory collaterals in the graft are more potent in the graft than in the normal hippocampus, and/or GABAergic inhibition is less efficient in the graft.

Restoration of rhythmic slow activity (theta) in the subcortically denervated hippocampus by fetal CNS transplants.

Solid pieces of the fetal septal region (SG) or hippocampus (HPC) were implanted in a cavity formed by aspiration of the fimbria fornix (FF) and the overlying cingulate cortex on one side in adult rats. In other lesioned animals cell suspensions obtained from the fetal septal area (SS) or the locus coeruleus region of the brainstem (LC) were injected stereotaxically into the deafferented host hippocampus. Six to 9 months after transplantation the animals had chronic recording electrodes implanted into both hippocampi. EEG and unit activity were monitored during running in a wheel, drinking and immobility. Unilateral fimbria-fornix lesions abolished rhythmic slow activity (RSA or theta, theta) in the ipsilateral hippocampus and no recovery was seen up to 9 months later in either the control FF-lesioned animals or in the rats with LC suspension grafts. Recovery of RSA, however, was observed in all animals with solid septal grafts and in some rats with solid HPC grafts. Similar to normal rats, RSA was present only during running and absent during drinking and sitting still. Coherence measurements of RSA between the transplanted and intact hemispheres resulted in high values (0.70-0.95). Concurrent with RSA, interneurons and granule cells in the host hippocampus fired rhythmically at RSA frequency (6-9 Hz). The depth profile and the antero-posterior distribution of the power of RSA correlated with the amount and distribution of the graft-induced acetylcholinesterase-positive reinnervation of the host hippocampus. In contrast to the animals with solid septal grafts, placed within the FF lesion cavity, the rats with intrahippocampal septal suspension grafts displayed only short duration bursts of RSA, and mainly during immobility. Based on these findings it is suggested that at least a proportion of the RSA 'pacemaker' cells of the host septum survives the transection of the fimbria-fornix fibers and that a graft of fetal septal or hippocampal tissue implanted into the lesion cavity may be capable of relaying this pacemaker activity to the host hippocampus. This effect may be due to the ability of the grafted tissue to promote the regeneration of new, direct or indirect, septo-hippocampal connections across the lesion cavity.

Laminar distribution of hippocampal rhythmic slow activity (RSA) in the behaving rat: current-source density analysis, effects of urethane and atropine.

This study investigated the laminar distribution of rhythmic slow wave activity (RSA) in the dorsal hippocampus of the rat during running. Depth analyses of field EEG were performed by stepping the recording electrode in 82.5 micron increments and sampling RSA at each depth. One-dimensional current-source density (CSD) was calculated from the RSA profiles to enhance spatial resolution of current sources and sinks. Laminar analysis of power, coherence, and phase of RSA with respect to a stationary electrode in the stratum oriens of CA1 was performed with spectral methods. RSA waves in the CA1-dentate axis had power maxima at about the hippocampal fissures, hilus, outer molecular layer of the endal leaf of dentate gyrus and stratum oriens of CA1, in that order. A gradual shift of phase occurred in stratum radiatum of CA1. Large phase-shifts were found in both the endal and ectal leaves of the fascia dentata. A null zone and associated sudden phase-reversal of RSA were observed in stratum lucidum of CA3. Multiunit activity showed phase-locked modulation with RSA in the granule cell layer of the dentate gyrus and pyramidal cell layer of CA1, CA3, and subiculum. CSD analysis in the CA1-dentate axis revealed multiple source-sink pairs. The sinks and sources showed cyclic changes with RSA, and were attributed to the rhythmic, but time-shifted, activity of hippocampal afferents from the septum and entorhinal cortex. The gradual phase-shift in CA1, and the configurational changes of RSA waves with depth, are explained by the summation of extracellular currents produced by time-delayed sink-source pairs (RSA dipoles). When the cholinergic septohippocampal path was blocked by atropine a null zone in the middle of stratum radiatum of CA1 occurred and the phase-shift of RSA became steeper. Under urethane anesthesia a null zone was present in the inner stratum radiatum associated with a sudden phase-reversal of RSA. Urethane reduced the power of RSA in the hilus and decreased the firing rate of the granule cells. It is suggested that field RSA is produced by several rhythmical dipoles along the somadendritic surface of pyramidal cells and granule cells and the spatiotemporal relations of the individual dipoles determine the actually observed extracellular RSA.

Flash and pattern presentation and pattern-reversal evoked potentials in multiple sclerosis.

The visual evoked potential (VEP) results for 404 multiple sclerosis (MS) patients are presented. In 171 patients pattern reversal with light-emitting diode (PR (LED] VEPs and in 85 patients pattern reversal with TV (PR(TV] VEPs also were investigated. The pathologic process of MS affects the amplitude and latency of all components and the form and symmetry of responses. A complex evaluation of VEP is proposed instead of measurement of only one component. A combined flash and pattern presentation VEP evaluation may be as effective as PREPs in the detection of subclinical lesions. PR(LED) VEP seems to be more sensitive to the degree of visual disturbance and to the clinical probability of MS than the PR(TV) VEP. A statistical analysis disclosed correlation of VEP amplitude and latency data with the visual impairment, one with the duration and multiplicity (generalization) of the disease. Combination of different methods increases the discriminative power of the VEP investigation.