Paraneoplastic syndrome mimicking progressive supranuclear palsy

Paraneoplastic syndrome presenting with progressive supranuclear palsy (PSP) phenotype is extremely rare. We report a patient who presented with features of rapidly progressive parkinsonism similar to PSP and was found to have small cell carcinoma of the lung along with seropositivity for onconeural antigen. The patient was treated with immunomodulation and was given chemotherapy for the malignancy and subsequently improved.     

Cerebrospinal fluid analysis for Whipple's disease in patients with progressive supranuclear palsy.

The clinical picture of neurological involvement in Whipple's disease (WD) may resemble progressive supranuclear palsy (PSP). We looked for WD pathogen DNA in the cerebrospinal fluid of 9 patients with a clinical diagnosis of PSP. The analysis was negative for all samples, showing that WD is not commonly involved in the aetiopathogenesis of PSP.     

Eyelid movement abnormalities in progressive supranuclear palsy

We systematically videotaped eyelid movements in a community-based series of 38 patients with progressive supranuclear palsy (PSP). Ten patients (26%) had blepharospasm, "apraxia" of lid opening and/or "apraxia" of lid closing. These patients as a group had more severe upgaze paresis but no greater disease duration than the patients without supranuclear lid dysfunction. Patients used a variety of synkinetic movements to overcome lid-movement abnormalities. One patient displayed "slow blinks," a phenomenon not previously described in PSP. Blink rate in PSP, 3.0/min, was markedly lower than that in patients with Parkinson's disease (PD), 12.5/min, and patients with PSP but not PD increased their blink rate during command versional eye movements.     

Neurodegenerative disorders mimicking progressive supranuclear palsy: a report of three cases

Progressive supranuclear palsy (PSP) is rarely confused with other parkinsonian disorders once the vertical gaze palsy appears. Corticobasal degeneration is the most common differential diagnostic entity. We describe three cases diagnosed during life as PSP but found to have another neurologic disorder at autopsy. No explanation for the gaze palsies was found in any case.     

Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria

Background : PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective : We aimed to provide an evidence‐ and consensus‐based revision of the clinical diagnostic criteria for PSP. Methods : We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy‐confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2‐day meeting, and refined in three further Delphi rounds. Results : Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context‐dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions : Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society     

Co-occurrence of Parkinson's disease with progressive supranuclear palsy

Parkinson's disease (PD) and progressive supranuclear palsy (PSP) are distinct neurodegenerative disorders. We describe an 81-year-old woman with 3 years of progressive gait unsteadiness, frequent falls, and mild cognitive dysfunction, all considered clinically to be an early fronto-temporal neurodegenerative disorder. She died of an acute myocardial infarction. Examination of her brain revealed alpha-synuclein- and tau-positive inclusions diagnostic of PD and PSP. Immunoelectron microscopy and Western blot analysis confirmed combined PD/PSP. This case provides strategies for the reliable molecular validation of concomitant PD and PSP, and demonstrates the utility of these techniques in patients with atypical clinical presentations.     

A network approach to diagnostic biomarkers in progressive supranuclear palsy

Diagnosis of progressive supranuclear palsy (PSP) remains challenging because of the clinical overlap with Parkinson's disease (PD). To date, disease‐specific biomarkers have yet to be identified. In the absence of reliable biomarkers, we used an integrated network approach to identify genes and related biological pathways associated with PSP. We tested a highly ranked gene in cellular whole‐blood samples from 122 patients enrolled in the Prognostic Biomarker Study. Biological and functional analysis identified 13 modules related to activation of leukocytes and lymphocytes, protein dephosphorylation, and phosphatase activity. Integration of these results with those from microarrays identified ptpn1 as a potential biomarker for PSP. Assessment of biomarker performance revealed that ptpn1 could be used to distinguish PSP patients from PD patients with 86% diagnostic accuracy. Ptpn1 may be a diagnostic marker useful for distinguishing PSP and PD. Further evaluation in a larger well‐characterized prospective study is warranted. © 2013 International Parkinson and Movement Disorder Society     

Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy

OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.     

Epidemiology of progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a rare form of parkinsonism. The incidence rates are about 0.3–1.1 cases per 100 000 persons. The only two-case-control studies performed up to now show conflictual results as regards education and residence in rural areas. Recently, a cluster of PSP and atypical parkinsonism has been observed in French Antilles. The hypothesis is that a consumption of both tropical fruit and herbal tea may be associated with PSP onset. Some PSP families with a probably autosomal dominant transmission have been described. A high frequency of a tau haplotype (H₁/H₁) associated with PSP is reported by some authors. The significance of this association is still not clear. We have performed a case-control study on 58 PSP cases, 116 hospital controls and 58 population controls.     

Neuropathology of progressive supranuclear palsy

The fundamental neuropathological findings of progressive supranuclear palsy (PSP) are presented, based on 14 autopsied cases of PSP. The blunt pathologies of PSP are degeneration in the substantia nigra, globus pallidus, subthalamic nuclei, dentate nucleus of the cerebellum and red nucleus, where there are neuronal loss, gliosis and neurofibrillary changes, to varying degree. In addition, the atrophy of the midbrain, especially the characteristic pattern of tegmental atrophy of the pons exhibiting a hand-bag profile, is an important finding. Hypertrophy of inferior olivary nucleus is frequently observed, suggesting the existence of lesions in the dentato-olivary system. Hypoxemic affects at the agonal stage should be noted because death of Purkinje cells of the cerebellum leads to degeneration of their axons and subsequently to the decrease of grumose degeneration in the dentate nucleus. Familial PSP have been reported by several authors but all case in the present study were sporadic.     

Differential diagnostic value of eye movement recording in PSP-parkinsonism,Richardson's syndrome,and idiopathic Parkinson's disease

Abstract   Vertical gaze palsy is a highly relevant clinical sign in parkinsonian syndromes. As the eponymous sign of progressive supranuclear palsy (PSP), it is one of the core features in the diagnosis of this disease. Recent studies have suggested a further differentiation of PSP in Richardson's syndrome (RS) and PSP-parkinsonism (PSPP). The aim of this study was to search for oculomotor abnormalities in the PSP-P subset of a sample of PSP patients and to compare these findings with those of (i) RS patients, (ii) patients with idiopathic Parkinson's disease (IPD), and (iii) a control group. Twelve cases of RS, 5 cases of PSP-P, and 27 cases of IPD were examined by use of video-oculography (VOG) and compared to 23 healthy normal controls. Both groups of PSP patients (RS, PSP-P) had significantly slower saccades than either IPD patients or controls, whereas no differences in saccadic eye peak velocity were found between the two PSP groups or in the comparison of IPD with controls. RS and PSP-P were also similar to each other with regard to smooth pursuit eye movements (SPEM), with both groups having significantly lower gain than controls (except for downward pursuit); however, SPEM gain exhibited no consistent difference between PSP and IPD. A correlation between eye movement data and clinical data (Hoehn & Yahr scale or disease duration) could not be observed. As PSP-P patients were still in an early stage of the disease when a differentiation from IPD is difficult on clinical grounds, the clear-cut separation between PSP-P and IPD obtained by measuring saccade velocity suggests that VOG could contribute to the early differentiation between these patient groups.     

Loss of torsional quick eye movements during head roll in progressive supranuclear palsy: a new diagnostic marker

Journal of Neurology - Even though impaired horizontal and vertical saccades are well-known features of progressive supranuclear palsy (PSP), abnormalities of torsional quick phases of eye...     

A clinicopathological study of vascular progressive supranuclear palsy: a multi-infarct disorder presenting as progressive supranuclear palsy

BACKGROUND: Clinical features suggesting a diagnosis of progressive supranuclear palsy (PSP) include early falls, axial rigidity, vertical supranuclear ophthalmoplegia, and levodopa unresponsiveness. When these clinical features are present, the diagnosis is almost always PSP, yet vascular disease sometimes has a similar presentation, referred to as vascular PSP. OBJECTIVE: To evaluate clinical and pathologic features of cases of vascular PSP submitted to a PSP brain bank. DESIGN: Review of gross and microscopic neuropathological features, determination of tau haplotype, and medical record review of 4 patients with an antemortem diagnosis of PSP who did not meet the pathologic criteria for PSP and instead had vascular pathologic abnormalities. RESULTS: All patients had vertical supranuclear ophthalmoplegia, a history of falls, and a gradually progressive disease course. Falls began 1 year after symptom onset, and all patients had asymmetric findings on a neurological examination. A magnetic resonance imaging scan revealed lacunar basal ganglia infarcts in one patient and an increased T2-weighted signal in the corona radiata and centrum semiovale in another. Gross and microscopic neuropathological studies demonstrated infarcts in the cerebral cortex (n = 4), thalamus (n = 4), basal ganglia (n = 3), and cerebellum (n = 4). The brainstem was affected in one patient, but no infarcts were detected in the subthalamic nucleus or substantia nigra. Of the 4 patients, 3 carried an H2 tau haplotype, a rare occurrence in the general population. CONCLUSIONS: Asymmetric signs, falls after 1 year of symptom onset, vascular lesions on a magnetic resonance imaging scan, and an H2 tau haplotype may help differentiate vascular PSP from PSP. Thalamic and basal ganglia infarcts are common in patients with vascular PSP and, when present, may contribute to misdiagnosis.     

Creutzfeldt–Jakob disease presenting as progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by an akinetic rigid syndrome with vertical supranuclear ophthalmoplegia, early falls, and levodopa resistance. The pathological substrate of PSP consists of filamentous tau degenerative lesions affecting neurons and glia. Other disorders can present with a similar clinical picture, most commonly corticobasal degeneration and multiple system atrophy. Non-neurodegenerative disorders are rare causes of the PSP syndrome. In this report we describe clinical and pathological features of two cases of Creutzfeldt-Jakob disease (CJD) presenting with the PSP syndrome and discuss which features may help prevent misdiagnosis. To our knowledge, this is the first report of cases of CJD with autopsy confirmation that presented with a PSP syndrome.