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Alzheimer's disease: neuropathological correlates of cognitive and motor disorders.

Correlations between clinical symptoms and changes in brain neuropathology were investigated in 34 patients with Alzheimer's disease, who were compared with 17 non-demented, age-matched controls. The patients were originally found in a community survey of dementia and were followed up prospectively until death. A highly significant correlation emerged between the severity of dementia and the numbers of plaques and tangles in the material as a whole, but no essential difference was found between severely and less severely demented patients. Low brain weight correlated highly with many clinical symptoms and signs and the severity of dementia. A multiple regression model consisting of plaques and tangles in amygdala, gyrus frontalis medius, gyrus angularis, and gyrus temporalis medius, plaques of gyrus rectus, tangles of the hippocampus, gyrus precentralis and gyrus cinguli together with brain weight, emerged to link dementia to neuropathological changes at the level of maximum significance. Dyskinetic movements were associated with damage of several brain areas, implying a multiple etiology.

Alzheimer Disease↗

Cerebrovascular hypoperfusion: a risk factor for Alzheimer's disease? Animal model and postmortem human studies.

Although cognitive impairment during aging is usually associated with neuronal alterations, the cerebrovascular system undergoes prominent alterations in aging as well. Using electron microscopy we previously showed a progressive deterioration of the capillary wall in the cerebral cortex of aged rats. In aged rats the capillary basement membrane (BM) is thickened, massive bundles of collagen fibrils are deposited within the BM, and pericytes are degenerating. A compromized cerebral circulation (e.g., in rats with chronic hypertension) is characterized by an increased number of capillary alterations. In autopsy material (gray matter, gyrus cinguli) of carefully diagnosed patient groups (controls, AD, Lewy body disease, MID and demented Lewy body disease patients) we observed significantly more morphological changes in the capillary bed of demented versus non-demented patients. In both animal and human material morphological evidence points to a relation between energy-dependent nutrient transport across the blood-brain barrier and the ultrastructural deviations. In the AD cases we did not find a correlation between the stage of the disease (Braak I-VI) and the incidence of capillary aberrations, which indicates that the capillary alterations are not a consequence of AD pathology. Simultaneously, we are conducting animal model studies to determine the effects of cerebral hypoperfusion in the rat. Permanent bilateral occlusion of the carotid arteries shifts the behavioral profile of the rats (Morris maze, open field) towards that of aged rats, while the sensitivity for muscarinic ligand agents is altered.

Aging↗

Changes in the brain catecholamines in patients with dementia of Alzheimer type.

Brain monoamine concentrations were determined post mortem in 19 patients with dementia of Alzheimer type. Samples were taken from 10 parts of the brain and compared with an age-matched control group. There were lower mean concentrations of dopamine in the demented group of patients in seven regions of the brain, and two of these were at a significant level. There were also significantly lower concentrations of homovanillic acid in the nucleus caudatus and in the putamen. The means of the concentrations of noradrenaline were also lower, and in the putamen and the cortex gyrus frontalis significant differnces were observed. The 5-hydroxytryptamine concentrations were slightly lower in the demented group but the differences did not reach significance. The degree of intellectual deterioration was negatively correlated with the noradrenaline concentrations in the hypothalamus and the cortex gyrus cinguli.

Aged↗

Correlation between Apolipoprotein-E polymorphism and Alzheimer's disease pathology.

Alzheimer's disease (AD) and small vessel disease dementia (SVDD) are common causes of dementia. The ApoE genotype has been proposed as a risk factor for AD. The frequency of the three ApoE alleles was correlated with the neuropathological changes of AD (senile plaques, neurofibrillary tangles and amyloid angiopathy) and SVDD (status lacunaris, status cribosus, leucoencephalopathy, micronecrosis and vascular fibrohyalinosis) in order to validate previous ApoE genotyping results in AD and to identify pre-clinical AD. Representative cerebral regions (cortex, gyrus cinguli, putamen, hippocampus, white matter) from 28 AD cases, 7 SVDD and 38 non-neurological controls were studied using classical histological techniques and immunohistochemistry for tau protein and amyloid-beta. The frequency of the ApoE allele 4 was significantly increased not only in AD patients but also in aged controls. However, following a detailed histopathological examination was found 62% of this group to exhibit histological changes associated with AD in limited brain areas (entorhinal region, hippocampus and adjacent temporal cortex or entorhinal region and hippocampus, or only in the entorhinal region), but 87% of these cases were found to be ApoE4 positive. The significant differences found in the distribution of ApoE allele frequencies were more marked when these cases were excluded from the control group and included as AD cases. In contrast, the frequency of the ApoE allele 2 is significantly increased in SVDD patients. Using histological techniques we confirmed the clinical diagnoses of all cases and classified the AD patients according to the severity of cortical pathology related to AD, while re-grouping from the control group those cases which had no clinical history of the disease but exhibited typical AD and SVDD histological lessions which could be considered as "pre-clinical" forms of these diseases.

Journal Article↗

The effect of intrahippocampal administration of dopamine or apomorphine on EEG of limbic structures in the rabbit brain.

The effect of intrahippocampal injections of dopamine or apomorphine on the energy level of EEG from limbic structures in the rabbit was investigated. The EEG was recorded from gyrus cinguli anterior, hippocampus dorsalis, nucleus amygdalae, hypothalamus medialis, and nucleus caudatus. Both apomorphine and dopamine in doses used produced stimulatory effects. The effect of apomorphine did not appear after pretreatment with haloperidol (2 or 24 hr, 1 mg/kg sc). This suggests the presence of dopamine receptors of stimulatory type in the dorsal part of rabbit hippocampus. The data confirm the prolonged action of haloperidol.

Animals↗

[Diffusion-weighted magnetic resonance tomography--a new instrument in the diagnosis of Creutzfeldt-Jakob disease].

Creutzfeldt-Jakob's disease (CJD) is characterised by rapidly progressive dementia, ataxia, myoclonus, and several other neurological deficits. It generally affects older adults and occurs in sporadic, genetic and iatrogenic forms. Death occurs usually within one year after onset of the disease. The diagnosis is based on clinical criteria, neurophysiological and radiological findings, and confirmed by postmortal histopathology. During the last two years several cases of CJD have been reported with diffusion-weighted magnetic resonance imaging (MR) abnormalities, represented by increased signal intensity indicating reduced diffusion in basal ganglia and/or cortex cerebri. These abnormalities seem to be characteristic of CJD. We report a case of CJD in a 54-year-old woman who developed vertigo, nystagmus, ataxia, myoclonus, and dementia over a period of eight months. Diffusion-weighted magnetic resonance imaging showed increased signal intensity in corpus striatum and gyrus cinguli. The diagnosis was postmortally confirmed with histopathology.

Brain↗

[Evaluation of alcoholic intoxication depending of the level of brain ethanol-metabolizing enzymes in death from ischemic heart disease].

Activities of alcohol dehydrogenases (ADG), aldehyde dehydrogenases (AlDG), and NADH+ dehydrogenases were measured by histochemical methods in neurons and capillaries of the gyrus cinguli and medulla oblongata of subjects dead from coronary disease. Enzymatic activities were found to depend on the stage of alcoholic intoxication. During resorption, characterized by reversible ethanol oxidation, the activities of AlDG and NADH+ dehydrogenases decreased, while during elimination the activities of these enzymes increased. ADG activity in cerebral tissue was increased during the entire period of alcoholic intoxication. The duration of alcoholic intoxication is determined by the amount of consumed ethanol and activity of AlDG. These regularities can be used for forensic medical evaluation of the role of alcoholic intoxication in coronary death.

Alcohol Dehydrogenase↗

Depth electroencephalography in selection of refractory epilepsy for surgery. Our experience with the suboccipital approach.

Despite new diagnostic tools, the precise localisation of an epileptic focal discharge remains an important step in the surgical treatment of epilepsy. Conventional EEG not always gives enough information to decide about surgery and more invasive methods have to be used. Epidural, subdural, and intra-parenchymatous electrodes have been used to come closer to the epileptic foci. Superficial hemispheric foci are well recorded by conventional epidural or subdural, strip or grid electrodes. Deeper foci, located in the medial temporal lobe or limbic areas are much more difficult to access from surface electrodes and other methods have to be used. Stereotactic placed multielectrodes and foramen ovale electrodes are most commonly implanted. Since 1986 we have used multi-contact cylindrical soft subdural electrodes. At the beginning we made the electrodes in our Department. Later on they were commercially available. In our Clinic the electrodes are usually introduced via a suboccipital approach and directed to the medial aspects of the temporal lobes until the temporal poles on both sides. Usually a median electrode located in the interhemispheric fissure, and covering gyrus cinguli is also placed. Out of 60 procedures done for different kinds of epilepsy, including cases with tumour or other surgical epileptogenic lesions, a total of 14 patients with genuine temporal lobe epilepsy have been studied and operated by this method. The advantages of the method as compared to stereotactic intraparenchymatous implanted electrodes are: less risk of bleeding and the fact that the brain tissue in those sensitive areas remains intact. Compared to foramen ovale electrodes our technique covers larger area of the temporal lobes and allows to insert a medial limbic electrode, but demands 2 burr holes. A further advantage of our technique is that the electrodes remain in place until surgery, allowing for their use as anatomical landmarks for tailoring the extension of the resection. This approach has been found to be simple, safe and reliable. A further improvement may be the simultaneous use of PEG epidural electrodes to obtain an overall view of the electrical activity of the brain including surface, deep temporal and midline cortical areas.

Brain↗

CT findings in the infantile form of citrullinemia.

Citrullinemia is a rare autosomal recessive inborn error of the urea cycle due to a deficiency in argininosuccinic acid synthetase. We present two cases of the infantile form of citrullinemia in which CT revealed bilateral and symmetric corticosubcortical hypoattenuating areas, ulegyric changes, and atrophy in the frontal lobes, as well as atrophy in the gyrus cinguli, insulae, and temporal lobes.

Atrophy↗

[Brain acetaldehyde and ethanol: method of determination and diagnostic significance in ethanol poisoning].

The content of ethanol and acetaldehyde in the limbic cortex and reticular formation of the brain was measured by gas-liquid chromatography in lethal ethanol poisoning. The content of acetaldehyde was significantly increased in the gyrus cinguli of the brain. Lethal poisonings occurred during any stage of ethanol intoxication. The data characterizing individual ethanol tolerance were obtained, which can be used for differential diagnosis of ethanol poisoning in practical forensic medicine.

Acetaldehyde↗

[One cannot be careful enough in the choice of one's parents--on the biopsychosocial development of adaptation systems for distress in Homo sapiens].

Actual results of brain research show that we might have more than one system to cope with distress. The most archaic one might be the system freeze/dissociation. The second one is the system attachment/relationship/herd/support. Articles by Allan N. Schore show that the central regulation of the self, the affects, and the interpersonal relations are impaired permanently by relational traumata/attachment traumata during early childhood. Jaak Panksepp differentiates the distress systems panic versus fear. On the one side we find the cluster panic--periaqueductal gray PAG--lateral septum--gyrus cinguli--glutamate--opioids--attachment--parasympathetic autonomic nerve system--trophotorphic state--hypometabolism--freeze reaction--dissociation, on the other side the cluster fear--enemy--sympathetic autonomic nerve system--ergotrophic state--hypermetabolism--fight and flight--cognition and learning. It can be helpful for therapy strategies to differentiate these systems.

Adaptation, Psychological↗

[Treatment of deep brain arteriovenous malformations].

BACKGROUND AND PURPOSE: The results of the treatment of patients with deep, supratentorial arteriovenous malformations (AVMs) located in medial hemisphere or intraventricularly are presented. MATERIAL AND METHODS: The paper presents the results of treatment of 17 patients. AVMs were located in the trigonum of the lateral ventricle in 4 cases (23.5%), in the splenium of the corpus callosum and its neighborhood in 4 cases (23.5%), in the parahippocampal and lingual gyrus in 3 cases (17%), in the head of the caudate nucleus in 2 cases (12%), in the hippocampus and the nucleus amygdalae in 2 cases (12%), in the anterior part of the gyrus cinguli in 1 case (6%) and in the truncus of the corpus callosum in 1 case (6%). RESULTS: AVMs most often manifested as intracerebral or subarachnoid hemorrhage (82%). The surgical treatment has been applied (total removal--90%), embolization with histoacryl glue (total embolization--20%) and irradiation with LINAC. The surgical treatment was performed in all patients with hemiparesis and intracerebral hematomas. CONCLUSION: The results of the surgical treatment are good and it fastest prevents recurrent hemorrhage from deep AVM. Incomplete embolization of AVM without the surgical treatment or radiosurgery is life threatening for the patients.

Adolescent↗

[Time perception in functional brain imaging].

BACKGROUND: Knowledge of physiological mechanisms underlying time perception is still rather limited. The aim of our study was to search for a 'time accumulator', i.e. the part of the brain where information on the duration of time is stored. METHODS AND RESULTS: Nine healthy volunteers were given a time reproduction task during event-related fMRI. Subjects were instructed to retain the duration of the stimulus presented (presentation phase) and then to reproduce it by pressing a button (reproduction phase). Two different analyses were made: event-related (P < 0.05, FWR corrected) and parametric (BOLD signal increase/decrease during the presentation/reproduction phases correlated with the time intervals; P < 0.01, FDR corrected). When the event-related approach was employed, activation was noted bilaterally in the inferior prefrontal cortex (IPFC), supplementary motor area (SMA), precuneus and secondary visual cortex. On the right, there was activation in the dorsolateral prefrontal cortex (DLPFC), gyrus cinguli and inferior parietal lobule. On the left, the primary sensory-motor cortex was activated. While during the presentation phase the left DLPFC activity inversely correlated with the presented duration, a nearly identical area showed positive correlation in the reproduction phase. CONCLUSIONS: The event-related analysis did not allow distinguishing the process of time perception from many cognitive processes running simultaneously. In turn, the parametric analysis was based on visualizing regions, in which the signal correlated with the varying duration of the time interval provided the level of attention, decision-making and the processes of behavioral response planning and execution were constant. Moreover, the right and left DLPFC seem to play different roles in time perception. While the left one is functioning as a "time accumulator", the right one is rather involved in the recognition of previously perceived intervals.

Adult↗

Organization of the cortico-ponto-cerebellar pathway to the dorsal paraflocculus. An experimental study with anterograde and retrograde transport of WGA-HRP in the cat.

To reveal the organization and relative magnitude of connections from various parts of the cerebral cortex to the dorsal paraflocculus via the pontine nuclei, WGA-HRP was injected in the dorsal paraflocculus in conjunction with injection of the same tracer in various parts of the cerebral cortex in 17 cats. Termination areas of cortical fibres (anterogradely labelled) and pontine neurons projecting to the dorsal paraflocculus (retrogradely labelled) were carefully plotted in serial transverse sections. As an average of countings in ten cats, 90% of the labelled cells were found in the pontine nuclei contralateral to the injection, and the majority (70%) were located in the rostral half of the nuclei. The highest degree of overlap between anterograde and retrograde labelling was found after injections of the parietal association cortex (areas 5 and 7). In an experiment with double anterograde tracing, it was shown that both area 5 and 7 contribute substantially to the cerebral inputs to the dorsal paraflocculus. High degree of overlap also occurred after injections of several visual cortical areas (areas 17, 18, 19, 20 and the posteromedial lateral suprasylvian visual area, PMLS). Cases with injections restricted to individual visual areas indicate that they all contribute to the parafloccular input. Considerably less overlap occurred after injections of the primary sensorimotor region (SI, MI) and second somatosensory area (SII), while the supplementary motor area, the auditory cortex and gyrus cinguli probably have no or very restricted access to the dorsal paraflocculus. It is concluded that the dorsal paraflocculus has its major cortical input from the parietal association cortex and the visual cortical areas. Since all the various cortical regions studied project to largely different parts of the pontine nuclei, and overlap with neurons projecting to the dorsal paraflocculus takes place at numerous places, it follows that the pontine neurons projecting to the dorsal paraflocculus must consist of many subgroups differing with regard to their cortical input.

Animals↗

[Psychomotor epilepsy: phenomenology, localization, pathogenesis and therapy].

Next to tonic-clonic seizures psychomotor (complex focal) seizures are the most common form of all epileptic seizures, except in infancy where they are seen rarely. Differently from generalised non convulsive seizures (like petit mal absences), their first appearance has no typical age limit, however, their proportion to other forms of seizures increases in adolescence and adults especially between the third and fifth decade of life. The main symptom is the disorder of consciousness which lasts at least more than half a minute, normally several minutes in completely distinct seizures, which doesn't begin abruptly and which often ends ill defined. This twilight attack is proceeded by an aura of sensory, psychic or vegetative character. The aura is followed either by a transitory state of immobility and later by motor phenomena or at once by motor phenomena in the form of diverse automatisms of variable intensity, reaching from mild movements in the oral region over verbal expressions to highly dramatic scenes, often accompanied by vegetative symptoms. Tonic versive and tonic symmetrical or tonic asymmetrical seizure symptoms are quite often motor variants which also can lead to sudden drops. Psychomotor attacks can be reduced to "pseudo-absences", however, they also can develop into tonic-clonic seizures (Grand mal). Generally, the succession of seizure symptoms is constant in the same patient, the expression can differ from seizure to seizure. Psychomotor attacks can be spread over the whole day or can show a strict connection to sleep, in the course they can likely occur in clusters and can accumulate to a continuous or discontinuous form of psychomotor status epilepticus. Predominantly, but not exclusively psychomotor attacks start from the temporal lobe, whereas neocortical temporal attacks (especially of lateral posterior origin) can be distinguished from those coming from the limbic system, especially from hippocampal or mesio-basal temporal structures and from the nucleus amygdalae. About 20% of the psychomotor attacks are of frontal origin coming from the mesial frontal region or from the gyrus cinguli anterior. Also seizures of occipital or parietal origin can spread so quickly that the seizure itself is impressing as a "temporal lobe attack". On account of that, epilepsies with psychomotor attacks cannot be compared to temporal lobe epilepsies. The etiology of psychomotor epilepsies is closely connected to the topographic site of the temporal lobe, who is especially vulnerable for traumatic lesions, cerebral edema and hypoxemia. Also small dysgeneses, heterotopies or small abnormalities of vessels are relatively often found in surgical specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Comparative evaluation of the levels of water-soluble glial fibrillary acidic protein in the human brain in the normal state and in schizophrenia].

The concentration of water-soluble glial fibrillary acidic protein was measured in several regions of human brains (12 schizophrenic patients and 13 patients without any signs of mental disease) using ELISA technique. The content of this protein was lower in thalamus and gyrus cinguli in schizophrenics as compared to normals (p less than 0.01). The protein showed no correlation with sex, age and the terms of autopsy (5 to 7 h after death). The findings suggest that decreasing concentration of the protein might reflect the changes of its synthesis, posttranslational modifications, assembling and disassembling of glial filaments and possibly the effect of psychotropic drugs.

Aged↗

The effect of apomorphine injection into caudate nucleus on electrical activity of some structures of the rabbit brain.

The studies were carried out on rabbits with chronically implanted electrodes and cannulas. Apomorphine, dopamine, or haloperidol were injected into the caudate nucleus of wakeful rabbits at a volume of 2 microliter. EEG was recorded from gyrus cinguli anterior, nucleus dorsalis raphe, and dorsal part of hippocampal formation. Apomorhine produced a dose-dependent desynchronization of EEG in the structure tested. This effect did not appear when dopaminergic receptors were blocked by previous systemic (1.2 mg/kg) or intracaudal (10microgram) injection of heloperidol.

Animals↗