Progressive supranuclear palsy: Neuropathology of patients with a short disease duration due to unexpected death.

Progressive supranuclear palsy (PSP) presents with a wide variety of signs/symptoms, making early initial diagnosis difficult. We investigated the clinical and neuropathological features of five patients with autopsy-proven PSP of short duration, ranging from 11 to 41 months (average, 26.2 months) due to unexpected death, focusing particularly on the distribution and severity of neuronal loss as well as neuronal and glial tau pathology in the affected brain. Clinical features were studied retrospectively through careful review of the medical records, and neuropathological examinations were carried out, along with tau immunohistochemistry using a monoclonal antibody AT8. These patients were diagnosed as having probable PSP (n = 4) and suggestive PSP (n = 1), respectively. In all cases, neuronal loss was evident in the substantia nigra, subthalamic nucleus, globus pallidus, and locus ceruleus. AT8-identified tau lesions, that is, pretangles/neurofibrillary tangles (PTs/NFTs), tufted astrocytes (TAs), and coiled bodies/neuropil threads (CBs/NTs), were distributed widely in the brain regions, especially in patients with longer disease duration. All cases showed variation in the regional tau burden among PTs/NFTs, TAs, and CBs/NTs. There was also a tendency for tau deposition to be more predominant in neuronal cells in the brainstem and cerebellum and in glial cells in the cerebral cortex and subcortical gray matter. These findings suggest that in PSP, the initial signs/symptoms are associated with degeneration and subsequent death of neurons with pathological tau deposition, and that the tau deposition in neuronal cells is independent of that in glial cells.

Pathology and sensitivity of current clinical criteria in corticobasal syndrome.

The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four-repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p-CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr-CBD) at the later stage. Only two patients fulfilled the criteria for either p-CBD or cr-CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset.

Familial Creutzfeldt-Jakob disease with a V180I mutation: comparative analysis with pathological findings and diffusion-weighted images.

BACKGROUND: Diffusion-weighted imaging (DWI) has been reported to be a useful technique for diagnosing Creutzfeldt-Jakob disease (CJD). The present study reported DWI results in cases of familial CJD with a V180I mutation (CJD180) in the prion protein gene as well as neurological findings. METHODS: A retrospective analysis of 3 patients with V180I was performed. Cerebrospinal fluid (CSF) analysis, brain MRI, single-photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS) were included. CSF was analyzed for biochemical markers, and each patient underwent brain MRI, SPECT, and MRS analysis. A brain biopsy from the frontal cortex, which corresponded to the area of increased DWI signals, was utilized for neuropathological analysis. RESULTS: CSF analysis results revealed elevated total tau protein and the absence of 14-3-3 protein, as well as decreased concentrations of neuron-specific enolase, S100 protein, and prostaglandin E(2). All patients presented with unique MRI features. Brain biopsy showed severe spongiform morphology, but comparatively preserved neurons and mild astrocytic gliosis. Accumulations of PrP(Sc) were not detected using the 3F4 antibody, and microglial activation was subtle. SPECT revealed hypoperfusion throughout both hemispheres. MRS revealed a reduced N-acetyl aspartate/creatine ratio. CONCLUSION: Results from this study suggested that increased DWI signals could reflect severe spongiform changes in CJD180 patients.

[Serial diffusion-weighted MRI (DWI) in a patient with sporadic Creuztfeldt-Jakob disease].

Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease.

[A case of extramedullary multiple myeloma manifested as an epidural mass in the cervical spinal cord].

A 76-year-old man who rapidly developed quadriparesis was admitted to our hospital. MRI showed an epidural mass extending from C4 to C6, displacing the spinal cord anteriorly. It showed isointensity on the T1-weighted imagines, hyperintensity on the T2-weighted images, and diffuse hyperintensity with gadolinium enhancement. Plain radiographs, CT and MRI showed no evidence of bone involvement. Serum immunoelectrophoresis disclosed M-components of IgA and lambda light chains. This is the first report that an epidural myeloma in the cervical spinal cord caused compression of the cord without evidence of bone involvement.