Neuropathology of variants of progressive supranuclear palsy. Curr Opin Neurol
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA. Current opinion in neurology
(Impact Factor: 5.31).
08/2010; 23(4):394-400. DOI: 10.1097/WCO.0b013e32833be924
Neurodegenerative tauopathies, of which progressive supranuclear palsy (PSP) is one of the most common, are clinically heterogeneous, reflecting differences in distribution and biochemical composition of tau pathology. This review highlights the range of clinical and pathologic presentations of PSP and its variants.
Progressive supranuclear palsy is a 4R tauopathy with neuronal and glial tau-immunoreactive lesions in neuroanatomically specific nuclei in the basal ganglia, diencephalon, brainstem and cerebellum, with restricted involvement of the neocortex. Hierarchical cluster analyses of clinical and pathologic features of PSP indicate that there are distinct clinicopathologic variants of PSP. In variants of PSP presenting with focal cortical syndromes, such as frontotemporal dementia, corticobasal syndrome and apraxia of speech, there is greater cortical pathology than in typical PSP. In variants of PSP presenting with levodopa-responsive Parkinsonism, as well as pure akinesia and gait failure, there is less cortical pathology and more severe degeneration in the cardinal nuclei - globus pallidus, subthalamic nucleus and substantia nigra - than in typical PSP.
Clinical variants in PSP reflect varying anatomical distribution of tau pathology, but they share histopathologic, biochemical and genetic features with typical PSP. The basis for anatomical selective vulnerability in PSP and its variants remains to be determined.
Available from: Shinsuke Fujioka
- "Patients with PSP typically present with an akinetic-rigid syndrome, supranuclear gaze palsy, cognitive impairment, and falling that is present at the onset of their illness . Pathological hallmarks are neurofibrillary tangles, coiled bodies, tufted astrocytes, and neuropil threads immunoreactive for 4-repeat tau . "
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ABSTRACT: To describe the clinical, pathological, and genetic features of three sib-pairs of pathologically-confirmed progressive supranuclear palsy (PSP).Methods
We searched the Mayo Clinic neurodegenerative diseases brain bank for cases of PSP in which more than one family member had pathologically-confirmed PSP. Clinical and pathological data were reviewed and all individuals were screened for mutations in MAPT, by sequencing exons 1, 7, and 9 - 13.ResultsWe identified three sib-pairs of pathologically-confirmed PSP. Sufficient information was available to suggest an autosomal dominant inheritance in two. The mean age at symptom onset was 41 years in one pair, and 76 in the other two. The young onset pair had a p.S285R mutation in MAPT, but no mutations were detected in the other two.Conclusions
All sib-pairs had typical pathological features of PSP; however, the age at onset of the sib-pair with MAPT mutation was significantly younger than sporadic PSP. Future studies are warranted to identify a possible genetic basis for PSP associated with late onset and typical PSP pathology.
Available from: Geneviève Leuba
- "1 SD No motor symptoms Not available Luzzi et al. (2012) 1 SD CBS Not available in the FTLD spectrum (Kertesz & McMonagle, 2010; Matuszewski et al., 2009; Pillon et al., 1995). Consistent with these findings is the known association of CBD with the other two clinical FTLD syndromes , progressive nonfluent aphasia and a behavioral variant of frontotemporal dementia (Kertesz et al., 2007; Kouri, Whitwell, Josephs, Rademakers, & Dickson, 2011; Murray et al., 2007; Rabinovici & Miller, 2010). Frontal behavioral manifestations are present in four of the reported SD–CBD cases (Ikeda et al., 1996; Mathuranath et al., 2000; McMonagle et al., 2006; Raggi et al., 2007), while abnormal performances on executive testing are reported in the fifth one (Luzzi et al., 2012). "
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ABSTRACT: A 57-year-old male with no family history was diagnosed with semantic dementia. He also showed some unusual cognitive features such as episodic memory and executive dysfunctions, spatial disorientation, and dyscalculia. Rapidly progressive cognitive and physical decline occurred. About 1.5 years later, he developed clinical features of a corticobasal syndrome. He died at the age of 60. Brain autopsy revealed numerous 4R-tau-positive lesions in the frontal, parietal and temporal lobes, basal ganglia, and brainstem. Neuronal loss was severe in the temporal cortex. Such association of semantic dementia with tauopathy and corticobasal syndrome is highly unusual. These findings are discussed in the light of current knowledge about frontotemporal lobar degeneration.
Available from: Friedemann Paul
- "Nuclei most severely affected by NFTs are the globus pallidus, subthalamic nucleus and substantia nigra. Tau pathology usually spares the cerebral cortex except for the precentral gyrus (Dickson et al., 2010). "
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ABSTRACT: Detection and discrimination of neurodegenerative Parkinson syndromes are challenging clinical tasks and the use of standard T1- and T2-weighted cerebral magnetic resonance (MR) imaging is limited to exclude symptomatic Parkinsonism. We used a quantitative structural MR-based technique, MR-elastography (MRE), to assess viscoelastic properties of the brain, providing insights into altered tissue architecture in neurodegenerative diseases on a macroscopic level. We measured single-slice multifrequency MRE (MMRE) and three-dimensional MRE (3DMRE) in two neurodegenerative disorders with overlapping clinical presentation but different neuropathology - progressive supranuclear palsy (PSP: N = 16) and idiopathic Parkinson's disease (PD: N = 18) as well as in controls (N = 18). In PSP, both MMRE (Δμ = - 28.8%, Δα = - 4.9%) and 3DMRE (Δ|G*|: - 10.6%, Δφ: - 34.6%) were significantly reduced compared to controls, with a pronounced reduction within the lentiform nucleus (Δμ = - 34.6%, Δα = - 8.1%; Δ|G*|: - 7.8%, Δφ: - 44.8%). MRE in PD showed a comparable pattern, but overall reduction in brain elasticity was less severe reaching significance only in the lentiform nucleus (Δμ n.s., Δα = - 7.4%; Δ|G*|: - 6.9%, Δφ: n.s.). Beyond that, patients showed a close negative correlation between MRE constants and clinical severity. Our data indicate that brain viscoelasticity in PSP and PD is differently affected by the underlying neurodegeneration; whereas in PSP all MRE constants are reduced and changes in brain softness (reduced μ and |G*|) predominate those of viscosity (α and φ) in PD.
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