1/4. frontotemporal dementia: a clinical-pathological study.We report a 44-year-old female patient without any familial history of dementia presenting with increasing disturbances in behaviour and language followed by a progressive cognitive deterioration. Neuropsychological evaluation revealed a significant impairment on frontal lobe tests. A brain PET scan disclosed a severe frontal hypometabolism. The tentative diagnosis of frontotemporal dementia was made. Her condition rapidly worsened and she died 2 years after the beginning of her disease. Gross examination of the brain showed a selective symmetrical atrophy of both frontal and anterior part of the temporal lobes. Microscopical examination revealed severe neuronal loss in the frontal and anterior temporal cortex associated with gliosis and microvascular spongiosis in the superficial cortical layers in the absence of any specific neuronal or glial inclusions. These neuropathological findings were consistent with the diagnosis of dementia lacking distinctive histology. We discuss the nosology of the frontotemporal dementias, the diagnostic value of PET scan, the recent genetical developments which strongly support the pathogenic role of tau and we emphasize the importance of immunohistochemical examination for a definite neuropathological diagnosis.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
2/4. Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene.Genetic screening of 171 patients with frontotemporal lobar degeneration disclosed 14 patients, across nine pedigrees, with mutations in the intron to exon 10 in the tau gene, a region regulating the splicing of exon 10 via a stem loop mechanism. Thirteen of these patients had the 16 splice site mutation and one had the 13 splice site mutation. Affected members of all nine families presented with changes in behaviour and social conduct that were prototypical of frontotemporal dementia (FTD). In all patients with the 16 splice site mutation, the behavioural profile was characterized by disinhibition, restless overactivity, a fatuous affect, puerile behaviour and verbal and motor stereotypies. The single patient with the 13 mutation presented a contrasting picture of apathy and inertia. In addition, all patients had evidence of semantic loss. Pathologically, five of the six patients so far autopsied shared frontotemporal atrophy with involvement of the substantia nigra. The underlying histology was that of microvacuolar-type cortical degeneration with a few swollen cells. Tau pathology was widespread throughout the brain and present in neurones and glial cells, mostly in the frontal and temporal cortical regions. This was in the form of neurofibrillary tangles and amorphous tau deposits (pre-tangles); Pick bodies were not observed. Ultrastructurally, the tau filaments had a twisted, ribbon-like morphology distinct from the paired helical filaments of Alzheimer's disease. One patient died from an unrelated illness whilst in the early clinical stages of FTD. In this patient, cortical microvacuolar and astrocytic changes were absent, though there were scattered neurones and glial cells, immunoreactive to tau, throughout the cortical and subcortical regions. The disease process underlying the neurodegeneration within these inherited forms of FTD may therefore stem directly from early, primary alterations in the function of tau. All eight families with the 16 mutation seem to be part of a common extended pedigree, possibly originating from a founder member residing within the North wales region of great britain.- - - - - - - - - - ranking = 3keywords = behaviour (Clic here for more details about this article) |
3/4. Forensic issues and possible mechanisms of sudden death in rett syndrome.A 20-year-old female with an established diagnosis of rett syndrome was found dead in bed. There had been no history of recent deterioration in health and at autopsy no acute lesions were found. There was no evidence of trauma. Toxicological analysis of blood revealed therapeutic levels of carbamazepine and clonazepam. Death was attributed to the complications of rett syndrome, an uncommon developmental disorder characterized by autistic type behaviour, hypotonia, stereotyped movements, seizures and growth failure, caused by mutations in the MECP2 gene on the x chromosome. Establishing the precise cause of sudden death in individuals with rett syndrome may be difficult as epilepsy, defective autonomic nervous system control and cardiac arrhythmias may relate more to functional problems rather than to defects that can be demonstrated at autopsy. Thus, although there are a variety of well-documented underlying mechanisms that may cause sudden death in this condition, determining the exact sequence of events in an unwitnessed death may be more by inference and elimination, given the absence of pathognomonic and acute lethal lesions that are able to be found histopathologically. 'Complications of rett syndrome' may, therefore, be the most accurate designation when individuals with this condition are found unexpectedly dead and no anatomical cause of death can be identified at autopsy.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |
4/4. The late effects of necrotizing encephalitis of the temporal lobes and limbic areas: a clinico-pathological study of 10 cases.The clinical and neuropathological features are reported of 10 patients who had suffered, usually for several years, from the after effects of an acute or sub-acute necrotizing encephalitis of the limbic grey matter and of the adjacent temporal lobes. Emphasis is laid on the memory disturbance and on the behavioural and emotional aberrations that tended to occur and that are in some ways reminiscent of the kluver-bucy syndrome.- - - - - - - - - - ranking = 1keywords = behaviour (Clic here for more details about this article) |