How Progressive Supranuclear Palsy (PSP) is Mimicked and What is Mimicking PSP?

14 April 2014

PSP-like Features without PSP Cytopathology in Three Cases of Alzheimer’s Disease/Parkinson’s DiseaseProgressive supranuclear palsy (PSP) is a progressive disabling neurodegenerative disorder manifested clinically by vertical supranucelar gaze palsy or slowing of vertical saccades, prominent postural instability, and falls. Its neuropathological substrate is 4 repeat tau deposition as neurofibrillary tangles in the basal ganglia and brainstem and tuft-shaped astrocytes. Lewy body (LB) pathology [1-3], or even pure Alzheimer’s disease (AD) pathology, could mimic PSP-like clinical features as we experienced recently [4, 5]. Three autopsy cases of PSP mimickers (with LB, LB/AD, pure AD pathology) are reviewed with special reference to midbrain tegmentum atrophy on magnetic resonance imaging (MRI) studies and myocardial uptake of metaiodobenzylguanidine cardiac scintigraphy (MIBG) so that utility and potential pitfalls of these imaging studies are reconsidered for improved clinical diagnosis of PSP.Clinical findings (Table 1): All patients presented with supranuclear gaze palsy, neck dorsiflexion, parkinsonism, and dementia. Patient 3 initially responded to l-dopa treatment; clinical differential diagnosis from Parkinson’s disease (PD) was difficult. Normal MIBG uptake and midbrain tegmentum atrophy on MRI of patients 2 and 3 also supported the clinical diagnosis of PSP.Neuropathological findings (Table 1): Neurolopathological examination revealed patient 1 as PD, patient 2 as AD+limbic LB, and patient 3 as pure AD. No PSP cytopathology such as tuft-shaped astrocyte was observed. LBs of patient 2 were restricted to the limbic system, and scarce in lower brainstem. Patient 1 showed LBs in oculomotor nucleus. Patient 2 and 3 demonstrated 3 repeat dominant neurofibrillary tangles and abundant senile plaques in midbrain tegmentum.Table 1. Clinical, radiological, and neuropathological features of present patients. All patients presented with supranuclear gaze palsy, neck dorsiflexion, parkinsonism, and dementia. MIBG cardiac scintigraphies of patient 2 and 3 were normal. MRI of patient 2 and 3 showed midbrain tegmentum atrophy. Neuropathological diagnosis of patient 1 was Parkinson’s disease; patient 2 was Alzheimer’s disease and limbic Lewy bodies; and patient 3 was pure Alzheimer’s disease. y, year; MIBG, metaiodobenzylguanidine cardiac scintigraphy; MRI, magnetic resonance images; N/A, not available; eH/M, early heart/mediastinum ratio; LB, Lewy body; AD, Alzheimer’s disease; PD, Parkinson’s disease Four repeat tau deposition in the midbrain tegmentum in PSP may explain both disturbance in extraocular movement and midbrain tegmentum atrophy on MRI, characteristic of PSP [4, 5], especially when combined. Our patients 2 and 3 exhibited this combination, which is most probably explained by AD-type cytopathology in the midbrain tegmentum. Therefore, significance of tegmentum atrophy on MRI to predict PSP cytopathology remains to be clarified by correlative MRI studies followed by autopsy confirmation. Currently, suspicion of AD may be enhanced with clinical features (early memory loss, troubles in spatial recognition, myoclonus etc.) [6] and other features on imaging studies suggestive of AD [7].Usually myocardial uptake of MIBG is decreased in the presence of LB pathology. Therefore its normal uptake favors clinical diagnosis as in patients 2 and 3. Normal uptake of MIBG may be possible if LBs are restricted to limbic area and absent in the brainstem as seen in patient 2. LBs could be found in pontine paramedian reticular formation, oculomotor nucleus, superior coliculus, nucleus of Cajal, or rostral interstitial nucleus of medial longitudinal fasciculus [1, 2], to explain possible disturbance in extraocular movements. Although patient 1 also showed LBs in oculomotor nucleus, it remains to be clarified which lesions are responsible for PSP-like features due to LB pathology, because midbrain tegmentum atrophy has not well recognized on MRI and autopsy studies of LB disease.Underlying pathologies for PSP-mimickers are heterogeneous. They can mimic not only clinical features but also MRI findings and even MIBG findings. Autopsy confirmation is necessary to understand how PSP is mimicked and what is mimicking PSP.Naoki Kasahataa,c,*, Mariko Hagiwaraa, Hiroyuki Katob, Yoshio Miyazawad, Tetsumasa Kameie, Yoshihisa Makitaf, Toshiki Uchiharac aDepartment of Medicine, Division of Neurology and bDepartment of Laboratory Medicine, Tokyo Metropolitan Ohtsuka Hospital, cLaboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, dDepartment of Pathology, eDepartment of Neurology, Fujisawa Tokusyukai Hospital, fDepartment of Pathology, Makita General Hospital, *n_kasa-o@ohtsuka-hospital.toshima.tokyo.jpAcknowledgments This study is supported by Grants-in-Aid for Scientific Research Technology, Grant from Japan Foundation for Neuroscience and Mental Health, the Mitsui Life Social Welfare Foundation, and the Tokyo Metropolitan Institute of Medical Science project ‘Mechanism for Early Diagnosis and Prevention of Parkinson’s disease.’ This study was also supported by Clinical Research Fund of Tokyo Metropolitan Ohtsuka Hospital.References [1] Lewis AJ, Gawel MJ (1990) Diffuse Lewy body disease with dementia and oculomotor dysfunction. 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