- [Show abstract] [Hide abstract] ABSTRACT: Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder. Clinical diagnosis is difficult in the early stages as the disease often presents with non-specific psychiatric and neurological symptoms. To investigate the diagnostic potential of quantitative short TE in vivo MRS, and the nature and anatomical distribution of biochemical abnormalities in vCJD, localised single-voxel spectra (TE/TR 30 ms/2,000 ms) were acquired from three brain regions: thalami, caudate nuclei and frontal white matter. Metabolite concentrations and ratios from three patients with definite or probable vCJD were compared with eight normal age-matched controls. Abnormal signal on T2-weighted MRI was apparent in the pulvinar region in all vCJD patients; this region also showed greatly increased myo-inositol [MI] (mean 2.5-fold, P=0.01) and decreased N-acetyl-aspartate (NAA; mean 2-fold, P=0.01). Two patients also showed increased [MI] (z=17, 11; one with decreased NAA, z=-12) in normal-appearing caudate nuclei. The magnitude of metabolite abnormalities in the thalami in moderately advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols allow the measurement of MI, which adds discriminant power to the MRS examination.
- [Show abstract] [Hide abstract] ABSTRACT: Inherited prion diseases are caused by mutations in the gene which codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers in the brain and neurodegeneration; they include Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). We studied two patients with symptomatic inherited prion disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from the thalamus, caudate region and frontal white matter, metabolite levels and ratios were measured and z-scores calculated for individual patients relative to age-matched normal controls. MRS data were compared with structural magnetic resonance imaging. One fCJD case had generalised atrophy and showed increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the frontal white matter. Both asymptomatic gene carriers had normal imaging, but increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in the caudate (z=5.3). Isolated MI abnormalities in asymptomatic gene carriers are a novel finding and may reflect early glial proliferation, prior to significant neuronal damage. MRS provides potential non-invasive surrogate markers of early disease and progression in inherited prion disease.
- [Show abstract] [Hide abstract] ABSTRACT: To assess cognitive function in variant Creutzfeldt-Jakob disease (vCJD). We describe the neuropsychological profiles of 10 cases and compare these data with cross sectional data obtained from patients with histologically confirmed sporadic CJD and cases with inherited prion disease with confirmed mutations in the prion protein gene. Patients referred to the Specialist Cognitive Disorders Clinic at the National Hospital for Neurology and Neurosurgery and the National Prion Clinic at St Mary's Hospital, London for further investigation of suspected CJD were recruited into the study. The neuropsychological test battery evaluated general intelligence, visual and verbal memory, nominal skills, literacy skills, visual perception and visuospatial functions, and visuospatial and executive function. The results indicate that moderate to severe cognitive decline is a characteristic feature of vCJD. Specifically, verbal and visual memory impairments and executive dysfunction were pervasive in all disease groups. Nominal skills were impaired in variant and sporadic CJD, significantly so when compared with the inherited prion disease group. Perceptual impairment was less frequent in the vCJD group than in the sporadic and inherited groups. This study confirms the occurrence of generalised cognitive decline in patients with vCJD. Although decline in cognitive function ultimately affects all domains, there is a suggestion that some components of visual perception may be spared in vCJD. The results also suggest that nominal function may be preserved in some cases with inherited prion disease.
- [Show abstract] [Hide abstract] ABSTRACT: Most cases of Creutzfeldt-Jakob disease (CJD) in recipients of human cadaveric growth hormone present with a cerebellar syndrome. Dementia is thought to occur late and as a minor feature of the illness. However, neuropsychology data published on these cases are largely qualitative and anecdotal. The first published case does include a neuropsychological assessment seven months after the onset of a cerebellar syndrome, showing evidence of intellectual decline. Subsequent reports hint that cognitive problems may be present in the initial stages of the illness. To assess early cognition in Creutzfeldt-Jakob disease in recipients of pituitary derived human growth hormone. Detailed neuropsychology assessment is reported at referral (mean 4.5 months from the onset of symptoms; range 4 to 6 months) in five patients with histologically proven human growth hormone derived CJD. All cases presented with a cerebellar syndrome and only one had noticed mild memory problems. On formal testing, however, four had demonstrable mild intellectual decline, as measured on the WAIS-R. One case showed selective visual memory impairment and frontal executive dysfunction. These findings suggest that, although not the presenting feature, mild cognitive decline may be evident in the early stages of CJD associated with human cadaveric growth hormone treatment.
- [Show abstract] [Hide abstract] ABSTRACT: The Royal College of Psychiatrists has recommended that old age psychiatrists may be best placed to take responsibility for service provision for younger people with dementia. There are concerns however, that if referral between specialists, particularly neurologists and old age psychiatrists, is incomplete, patients may be under investigated or inappropriately followed up. We have assessed the current level of referral between these specialists, how each investigates their patients and details of follow up care. We conducted a postal survey of all consultant neurologists and consultant old age psychiatrists in the UK with an overall response rate of 64%. RESULTS and The ideal of full collaboration between old age psychiatrists and neurologists is not achieved. Young patients may be under investigated if managed solely by an old age psychiatrist and may not receive adequate follow up services if managed solely by a neurologist.
- [Show abstract] [Hide abstract] ABSTRACT: To report a case initially fulfilling the clinical criteria for probable Alzheimer disease, although later clinical features suggested dementia with Lewy bodies. Oxygen 15-labeled positron emission tomograms revealed a pattern of hypometabolism characteristic of Alzheimer disease. At post mortem, there was no evidence of the pathological features of Alzheimer disease, but diffuse cortical Lewy bodies were seen in the pigmented brainstem nuclei and cerebral cortex. A case report. Tertiary referral center. A 65-year-old white man presented with a 3-year history of memory loss and language difficulties. Oxygen 15-labeled positron emission tomograms revealed hypometabolism in the frontal, temporal, and parietal lobes, more severe on the left than right. Metabolism in the left caudate was just outside the 95% reference range. Occipital metabolism was normal. Positron emission tomographic studies have been reported to show occipital hypometabolism in dementia with Lewy bodies, in addition to the characteristic posterior bitemporal biparietal pattern of Alzheimer disease. We suggest that although this finding may favor a diagnosis of dementia with Lewy bodies, it is not necessary for diagnosis.
- [Show abstract] [Hide abstract] ABSTRACT: A 58-year-old man died after a 27-month illness characterized by insomnia, confirmed by polysomnography. He was homozygous for methionine at codon 129 of the prion gene but had no mutation in the prion gene. Neuropathology showed thalamic and olivary atrophy and no spongiform changes. Paraffin-embedded tissue blotting demonstrated abnormal prion protein in the brain. This is the first case of the sporadic form of fatal familial insomnia with demonstration of the disorder by polysomnography. Ann Neurol 2000;48:665–668
- [Show abstract] [Hide abstract] ABSTRACT: This study reports a patient with severe, debilitating bilateral thalamic pain caused by bilateral thalamic infarcts. The authors consider it to be a unique case as a further clinically unilateral lesion led to pain relief bilaterally.