Biomedical subjects
Publications and source records attributed to C Duyckaerts.
Two cases of cerebral amyloid angiopathy with transient ischemic attacks are reported. Both patients died of cerebral hemorrhage. Transient ischemic attacks seem to having been due to the cerebral angiopathy a disease in which small infarcts are frequently mentioned at post-mortem examination. However only 6 other cases of transient ischemic attacks with cerebral amyloid angiopathy have yet been reported.
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Recent data favor the hypothesis of a genetically-induced overproduction of amyloid protein as the cause of Alzheimer's disease. This could be responsible for the occurrence of senile changes (senile plaques and neurofibrillary tangles) which are both characteristic of so-called normal aging of the brain and of Alzheimer's disease and lead to neuronal death. However, as shown by studies of twins, epigenetic factors must be very important in the triggering and/or acceleration of this process since the concordance between monozygotes does not reach higher levels than 41. It is argued that brain microglia, and/or astrocytes are the most likely candidates to the regulatory function of amyloid deposit in the brain. These cells could act by modulation of either the hydrolysis of the precursor protein during amyloidogenesis or the resorption of amyloid fibrils, which could occur in Alzheimer's disease as suggested by recent data. Further research on this topic could have therapeutical repercussions.
Counts of neurofibrillary tangles and senile plaques were performed in two adjacent sections from the temporal lobe in 14 women aged over 75 years at death. The mental status of these cases had been prospectively assessed by the test score of Blessed, Tomlinson and Roth. They were either intellectually normal or had senile dementia of the Alzheimer type of various degrees of severity. The first section was silver-impregnated according to Bodian's method; the second one was immunolabeled with an antiserum raised against neurofibrillary tangles. Densities of neurofibrillary tangles and senile plaques evaluated by the two techniques were highly correlated but their means of differences and limits of agreement were large. The correlation with the clinical data was similar for the two methods. Both techniques can thus be used with the same accuracy in correlative studies but their results are not interchangeable without caution.
In the brains of humans and other mammals, there are two principal groups of cholinergic nuclei aside from those forming the cranial motor nuclei. One group lies in the forebrain and includes the nucleus basalis of Meynert. The second group lies in the hindbrain and includes the nucleus tegmenti pedunculopontinus (NPP), identified by Mesulam et al. [Mesulam, M.-M., Mufson, E. J., Wainer, B. H. & Levey, A. I. (1983) Neuroscience 10, 1185-1201] as cholinergic cell group Ch5. The basal forebrain cholinergic cell groups, which innervate widespread areas of the neocortex, undergo degeneration in Alzheimer disease and also in parkinsonism associated with dementia. We here report that the hindbrain NPP Ch5 cell group, thought to innervate many nuclei of the extrapyramidal motor system, the superior colliculus, and the substantia innominata, undergoes degeneration in idiopathic Parkinson disease and in the parkinsonian syndrome of progressive supranuclear palsy. These findings strongly suggest that degeneration in the brainstem in Parkinson disease is not confined to catecholamine-containing neurons, but that cholinergic neurons of the NPP are also vulnerable. The findings further raise the possibility that certain symptoms of Parkinson disease and progressive supranuclear palsy have their genesis in pathology of these cholinergic neurons.
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Post-mortem study of every patient who died from AIDS in Pitié-Salpêtrire Hospital from June 1984 to November 1985 was performed without regard to the presence of neurological signs and symptoms. Autopsy were performed in 31/48 cases. Patients had been hospitalized in the Departments of Parasitology-Infectious Disease (24 cases) Internal Medicine (4 cases) and Neurology (3 cases). In every case, formalin-fixed material from the brain and the spinal cord were embedded in paraffin (20 samples), stained with hematoxylin-eosin, PAS, Alcian blue, Giemsa, Grocott and Ziehl techniques and Bodian's silver impregnation along with Luxol fast blue, and, in celloïdin (8 samples), stained with hematoxylin-eosin and Loyez' impregnation. There were 30 men (27 caucasian, 1 egyptian, 1 haïtian, 1 senegalese) and one woman (congolese). Twenty eight (28) patients were homosexuals. AIDS was transfusion-associated in two cases. Neurologic complications revealed the disease in 2 cases. Eighteen (18) patients had neurological signs or symptoms before death. Age range at death was 22-58 (mean 38). Brain weight in AIDS (from 1150 gms to 1750 gms-mean 1428 gms) was not statistically different from the mean weight of 100 male patients in the same age range autopsied in the same laboratory during the identical period (mean 1427 gms, standard deviation: 23). Microscopic abnormalities were present in every brain examined. These included non-Hodgkin lymphoma (3 cases), opportunistic infections (21 cases: 13 toxoplasmosis, 4 cytomegalovirus encephalitis, 3 cryptococcal meningitis, 1 infection by mycobacterium avium-intracellulare), and subacute encephalitis (17 cases, 9 isolated, 8 associated with other disorders). The characteristic changes consisted of lympho-monocytic focal infiltrates (so-called microglial nodules) and mild lympho-monocytic perivascular cuffs in 10 cases. Typical giant cells were seen only in one case. Mild demyelinating changes were also seen in only one case. No spinal cord spongiosis, nor Progressive Multifocal Leukoencephalopathy was found. HIV localization was performed on frozen sections utilizing in situ hybridization techniques (2 cases) and immunohistologic techniques (5 cases). HIV, RNA and proteins, was detected in 2 cases with subacute encephalitis. Infected cells were labeled with macrophage markers, and rarely with T4 lymphocyte markers. Infected astrocytes (identified by anti-GFAP serum) or neurons (identified by anti-NSE serum) were never observed. No giant cells were seen in these two cases.
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To investigate the possible alterations of spinal cord monoaminergic pathways in Parkinson's disease, the levels of dopamine, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid have been measured in different subregions of the lumbar spinal cord in control subjects and parkinsonian patients. Substantial amounts of these compounds were found in the dorsal, intermediate and ventral grey matter portions and in the white matter of the spinal cord; the levels of serotonin and its metabolite being the highest. In parkinsonian patients, lumbar spinal cord dopamine and homovanillic acid levels were similar to those in the control subjects, whereas the concentrations of noradrenaline, serotonin and its metabolites were clearly subnormal in the different parts of the cord, the depletion of noradrenaline being the most pronounced. These data suggest that lumbar spinal cord noradrenergic and serotonergic, but not dopaminergic, systems are damaged in Parkinson's disease.
A prospective longitudinal study was undertaken in a geriatric hospital on women over 75 years of age, clinically diagnosed as either intellectually normal or having senile dementia of the Alzheimer type (SDAT) of varying degrees of severity. Mental impairment was assessed prospectively. Fifteen brains from this population were studied to evaluate quantitatively the distribution of senile plaques (SP) in relation to cortical lamination. SP density in four neocortical areas (first temporal gyrus; supramarginal gyrus calcarine area; precentral gyrus) was significantly correlated with the degree of mental impairment. SP distribution in the cortical layers was evaluated by an indirect method and appeared to be fairly constant from one case to another. Significantly higher SP densities were observed in layers II and III of the temporal and occipital samples, while minimal values were noted in layer I. Lower densities of SP were found in layers V and IV of the occipital and temporal lobes. These data suggest a selective vulnerability of some areas of cortical projections in SDAT.
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The brains of 12 patients aged more than 100 years were studied neuropathologically. These were all women who had been long-stay patients at the Charles Foix Hospital, Ivry. On the basis of a retrospective examination of the clinical records the patients were classified as demented or non-demented. No attempt was made to evaluate their mental status more precisely because of the prevalence of deafness (in 10) and blindness (in 7) and also because of the difficulty in assessing mild cognitive changes in institutionalized patients. Three patients were considered to have been demented according to the criteria of the DSM3 (1980). In the brain of one demented case the pathology was that of Alzheimer's disease, in one there were multiple infarcts and in the third there were both senile and vascular changes. The findings in this study are in accordance with the reports of others and indicate that the incidence of senile dementia of the Alzheimer type is not increased in people of very advanced age. Neuropathological findings included reduced brain weight; neurofibrillary tangles in hippocampal neurons of every case as well as in neocortical neurons (absent from neurons of the substantia innominata in only 1 case); senile (neuritic) plaques were found commonly in the hippocampus, less so in neocortical areas (senile plaques totally absent in only one case); granulovacuolar degeneration in hippocampal neurons in every case; amyloid angiopathy present in 9 and mineralization of vessels in 10 cases; hyaline change in vessel walls and abundant lipofuscin in neurons and astrocytes were constant findings. No Lewy bodies were seen.
A 56-year-old man had radiation necrosis of the optic pathways, hypothalamus and brainstem following irradiation of a pituitary adenoma at a conventional dose. Factors which predispose to this complication are discussed. Vascular risk factors appear to facilitate radiation induced necrosis, and a reduction of doses is suggested in these cases.
A pure amnesic syndrome of 21 months' duration occurred in a 36-year-old man following a transient confusional state. The patient died of Hodgkin's disease. At postmortem examination, bilateral and symmetrical neuronal loss, without inflammatory changes, was restricted to the hippocampus and amygdaloid bodies.
In 9 patients with progressive supranuclear palsy and in 27 controls, dopamine and homovanillic acid concentrations, choline acetyltransferase (CAT) activity, and the number of [3H]spiperone and [3H]quinuclidinyl benzilate binding sites were measured post mortem in the striatum (caudate nucleus, putamen, and nucleus accumbens), substantia innominata, and frontal cortex. Dopamine and homovanillic acid concentrations were reduced in the caudate nucleus and putamen but not in the nucleus accumbens or frontal cortex, indicating that the nigrostriatal dopaminergic system is lesioned in patients with progressive supranuclear palsy (as in those with Parkinson's disease) but not the mesocortical and mesolimbic dopaminergic systems, which are lesioned in parkinsonian patients. CAT activity and [3H]spiperone binding decreased in parallel fashion in all the structures. In the striatum, this suggests that the cholinergic neurons, which are target cells of the nigrostriatal system, also degenerate in this disease. This might explain the decrease in the number of dopamine receptors as well as the inefficacy of levodopa or anticholinergic therapy in these patients. The decrease in CAT activity in the substantia innominata and the frontal cortex indicates that the innominatocortical cholinergic system is lesioned in patients with progressive supranuclear palsy and may play a role in the intellectual deterioration observed. This lesion is also found in demented patients with Alzheimer's and Parkinson's diseases.
The current views on the pathophysiology of cerebral ischaemia have recently been challenged by the new experimental results and animal models devised in recent years. These data are briefly reviewed. Ischaemic macroscopical and microscopical lesions in the human brain are outlined. Ischaemic changes can be either regional or total. The types, topography and aetiology of cerebral infarcts, lacunes and venous infarcts are described. The consequences of marked or total ischaemia affecting the whole cerebral blood supply are mentioned.
A prospective study was undertaken to select mentally normal old subjects and patients with senile dementia of the Alzheimer type (SDAT). The test score of Blessed et al. (1968) (BTS) was used to determine the severity of mental impairment. A pathologic study confirmed the diagnosis of either SDAT or normal brain aging at postmortem examination in 12 cases. The cortical area and the cortical perimeter of the different cerebral lobes were measured on 1-cm-thick coronal sections using a semiautomatic image analyzer. Cortical length and thickness were calculated using perimeter and area values. BTS was significantly correlated with both the area (r = 0.7695, P = 0.003) and the length (r = 0.7421, P = 0.006) of the temporal cortex. There was no significant correlation between BTS and thickness of the temporal cortex (r = 0.559, P = 0.059). These results show that reduction of length is one of the major determinants of cortical atrophy. Although this has to be confirmed by histological study, they favor the hypothesis of a column-selective atrophy in SDAT which should be considered in the interpretation of the microscopic data.