Brain Advance Access published online on December 24, 2007
Brain, doi:10.1093/brain/awm301
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Clinical and neuropathologic features of progressive supranuclear palsy with severe pallido-nigro-luysial degeneration and axonal dystrophy
1Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL and 2Department of Neurology, Mayo Clinic, Rochester, MN, USA
Correspondence to:
Dennis W. Dickson, MD, Neuropathology Laboratory, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA E-mail: dickson.dennis{at}mayo.edu
Pallido-nigro-luysial atrophy (PNLA) is a rare disorder that in many cases has histopathological features similar to progressive supranuclear palsy (PSP). In a pathological series of over 400 cases of PSP, eight cases were noted to have features similar to those described in PNLA, including severe atrophy and neuronal loss in the globus pallidus, substantia nigra and subthalamic nucleus, in addition to many axonal spheroids in the globus pallidus and substantia nigra. These eight cases of PSP–PNLA were compared to 11 typical PSP cases with quantitative neuropathologic indices and assessment of demographics, clinical features and the timing of clinical features. PSP–PNLA cases were younger, had longer disease duration and more often were not initially diagnosed with PSP; in the end, they did not differ from PSP with respect to any major clinical feature. The clinical course of PSP–PNLA, however, was different, with earlier gait abnormalities and difficulty with handwriting, but later falls, rigidity and dysphagia than PSP. Pathologically, the same types of lesions were detected in both PSP and PSP–PNLA, but there were differences in the distribution and density of tau-pathology, with less tau-pathology in motor cortex, striatum, pontine nuclei and cerebellum in PSP–PNLA. These clinical and pathological findings suggest that PSP–PNLA should be considered a variant of PSP.
Key Words: natural history; neuropathology; pallido-nigro-luysial atrophy; progressive supranuclear palsy; pure akinesia; tau
Abbreviations: CB, coiled-bodies; CN, caudate nucleus; DD, disease duration; DN, cerebellar dentate nucleus; GIF, gait ignition failure; GP, globus pallidus; MTR, motor cortex; NFT, neurofibrillary tangles and pre-tangles; NT, neuropil threads; PA, pure-akinesia; PAGF, pure akinesia with gait-freezing; PNLA, pallido-nigro-luysial atrophy; PPFG, primary progressive freezing gait; PSP, progressive supranuclear palsy; PSP-P, PSP-Parkinsonism; RN, red nucleus; RS, Richardson's syndrome; SCP, superior cerebellar peduncle; SN, substantia nigra; STN, subthalamic nucleus; TA, tufted astrocytes; VGP, vertical gaze palsy
Received August 13, 2007. Revised November 15, 2007. Accepted November 20, 2007.