Diagnosis Of Progressive Supranuclear Palsy Research Articles

Cerebral oxygen metabolism in patients with progressive supranuclear palsy: a positron emission tomography study.

To investigate cerebral oxygen metabolism in progressive supranuclear palsy (PSP), 5 patients with a clinical diagnosis of PSP and a variable degree of cognitive deficit were selected for positron emission tomography (PET) of the brain. In 4 of them, a significant decrease in oxygen metabolism was found in all cortical regions, without frontal accentuation. In the group as a whole, this decrease was even slightly more marked in parietal and temporal regions. These findings are not consistent with earlier PET studies that demonstrated frontal targeting of hypometabolism in PSP patients. Part of this discrepancy can be explained by differences in methodology, although the use of different clinical criteria and overlap of PSP with other neurodegenerative diseases must be taken into account. It is concluded that the absence of frontal hypometabolism on PET examination does not exclude the diagnosis of PSP.

Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop.

To improve the specificity and sensitivity of the clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski syndrome), the National Institute of Neurological Disorders and Stroke (NINDS) and the Society for PSP, Inc. (SPSP) sponsored an international workshop to develop an accurate and universally accepted set of criteria for this disorder. The NINDS-SPSP criteria, which were formulated from an extensive review of the literature, comparison with other previously published sets of criteria, and the consensus of experts, were validated on a clinical data set from autopsy-confirmed cases of PSP. The criteria specify three degrees of diagnostic certainty: possible PSP, probable PSP, and definite PSP. Possible PSP requires the presence of a gradually progressive disorder with onset at age 40 or later, either vertical supranuclear gaze palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset, as well as no evidence of other diseases that could explain these features. Probable PSP requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as the other features of possible PSP. Definite PSP requires a history of probable or possible PSP and histopathologic evidence of typical PSP. Criteria that support the diagnosis of PSP, and that exclude diseases often confused with PSP, are presented. The criteria for probable PSP are highly specific, making them suitable for therapeutic, analytic epidemiologic, and biologic studies, but not very sensitive. The criteria for possible PSP are substantially sensitive, making them suitable for descriptive epidemiologic studies, but less specific. An appendix provides guidelines for diagnosing and monitoring clinical disability in PSP.

Progressive supranuclear palsy: clinical and pathological diagnosis

Progressive supranuclear palsy (PSP) is an heterogeneous disorder, both clinically and pathologically and, in consequence, it is often difficult to diagnose. In this review we shall discuss those clinical settings in which it is difficult to make the diagnosis of PSP and review the pathology of the disorder. Clinical and pathological diagnostic criteria currently in use will also be discussed.

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

All cases examined postmortem at the Mayo Clinic that met the classic neuropathological criteria for progressive supranuclear palsy (PSP) were identified for retrospective clinical analyses. The necropsy material was re-examined by a second neuropathologist to confirm the pathological diagnosis of PSP, yielding 12 cases. A range of clinical signs were documented in these patients, with numerous findings beyond those noted in the original descriptions of this disorder. Atypical clinical findings included absence of supranuclear gaze palsy (two cases), prominent asymmetry (two), arm dystonia (two), upper limb apraxia (two), myoclonus (two), chorea (one), eyelid opening apraxia (one), and respiratory disturbance (one). A definite clinical diagnosis of PSP had been made during life in only eight of the 12 patients. From the retrospective analysis of these 12 cases, a set of clinical criteria were developed for the premortem diagnosis of PSP emphasising differences from other akinetic-rigid disorders.

Preliminary NINDS neuropathologic criteria for Steele‐Richardson‐Olszewski syndrome (progressive supranuclear palsy)

We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brain-stem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP.

The syndrome of 'pure akinesia' and its relationship to progressive supranuclear palsy

Five patients developed a stereotyped syndrome of progressive akinesia of gait, speech, and hand-writing without rigidity, tremor, or dementia. The symptoms did not improve with levodopa. These clinical findings conform to a syndrome described repeatedly in Japan since 1974 as "pure akinesia." Evidence has indicated that pure akinesia often represents a pre-ocular motor, and in some cases an ocular motor-sparing, form of progressive supranuclear palsy (PSP). Although we found disorders of eyelid movements, none of the patients demonstrated a gaze palsy on clinical examination. Four patients underwent eye movement recordings. The two patients with the longest disease duration had slow or small vertical saccades. These findings support the notion that patients with pure akinesia may develop a vertical gaze palsy, similar to that in PSP, late in their course. Our patients show that pure akinesia occurs in North America as well as in Japan. Recognition of the syndrome of pure akinesia may suggest the diagnosis of PSP before the development of abnormalities of ocular movement.

Progressive supranuclear palsy

To investigate potential heterogeneity in progressive supranuclear palsy (PSP), we examined 13 patients with neuropathologically diagnosed PSP. The clinical diagnosis of PSP was made in eight of these individuals, whereas probable AD was the primary diagnosis in the remaining five. In addition to PSP neuropathology, seven of the 13 patients (54%) showed concomitant pathologic changes of Alzheimer's disease (AD), Parkinson's disease (PD), or both disorders. These observations indicate that AD and PD changes coexist with PSP neuropathology in a substantive proportion of patients and provide further evidence of clinical and neuropathologic heterogeneity in neurodegenerative disorders. Moreover, our results suggest that PSP may be underdiagnosed and deserves more prominence in the differential diagnosis of dementing illness.

Role of pontine nuclei damage in smooth pursuit impairment of progressive supranuclear palsy: a clinical-pathologic study.

We performed a quantitative study of the pontine nuclei in the basis pontis and a semiquantitative study of extrapontine structures involved in smooth pursuit in four patients with severe impairment of horizontal smooth pursuit and histopathologically confirmed diagnosis of progressive supranuclear palsy (PSP). There were only slight changes in the extrapontine structures involved in smooth pursuit, but there was a significant neuronal loss--massive in three patients and mild in one patient--in all nuclei of the basis pontis. Our results suggest that degenerative lesions affecting the pontine nuclei are largely responsible for the horizontal smooth pursuit impairment in PSP.

Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities.

In studies of cerebral glucose metabolism utilising positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose, patients with the clinical picture of progressive supranuclear palsy (PSP) have shown predominantly frontal glucose hypometabolism. This is presumed to represent deafferentation of cerebral cortical from subcortical structures. In these studies, however, the diagnosis of PSP has not been verified by pathological examination. Necropsy examinations were performed in three patients with the clinical features of PSP in whom PET had demonstrated predominantly frontal hypometabolism. In two of these patients the diagnosis of PSP was confirmed pathologically, and no morphological abnormalities were found in the cerebral cortex. The third patient had extensive cortical and subcortical neuronal loss and gliosis without neurofibrillary tangles, consistent with the diagnosis of progressive subcortical gliosis (PSG). Even in retrospect no unique clinical neurological abnormality or finding on laboratory investigation could be identified that distinguished this latter patient from those with pathologically confirmed PSP. We conclude that PSG and PSP may be indistinguishable during life, and necropsy confirmation is needed for definite diagnosis.

Tremor in progressive supranuclear palsy

Reports of tremor in progressive supranuclear palsy (PSP) have been infrequent; some authors indicate that tremor is never seen in PSP. Five patients with PSP and tremor are presented. Our series of cases and those reviewed in the literature suggest that tremor occurs in 12-16% of PSP cases. The rest tremor observed in 3 of our cases differed from the "pill-rolling" and "parkinsonian tremor" described in previously reported cases by being slower in rate (3 per second or less). This slow rest tremor is rarely seen in Parkinson's disease (4-6 per second). Our experience suggests that, contrary to previous opinions, tremor may be the presenting complaint and a prominent finding in PSP and the presence or absence of tremor is of no value in the differential diagnosis of PSP from Parkinson's disease.

MR imaging in progressive supranuclear palsy and Shy-Drager syndrome.

Previous reports have suggested that putaminal hypointensity in T2-weighted images at high field strength (1.5 T) magnetic resonance (MR) is a common finding in atypical parkinsonian syndromes, including progressive supranuclear palsy (PSP) and Shy-Drager syndrome (SDS). We have reviewed nine patients with PSP and five with SDS, selected on strict clinical criteria. Only in one PSP patient was abnormal signal intensity (putaminal hypointensity more marked than pallidal) found. However, hypointensity was often marked in the substantia nigra and occasionally in the superior colliculi. Focal midbrain atrophy, involving particularly the upper part of the quadrigeminal plate, was obvious in five cases. In general there was no uniformity of findings and MR appears unable to consistently support the clinical diagnosis of PSP. In SDS patients the findings were more uniform, with hypointensity in the putamen, superior or equal to that of the pallidum. At low or intermediate field strength, there was absence of magnetic susceptibility effect in the putamen, which appeared hyperintense. This was probably because of increased water content due to gliosis and/or cell loss. The constancy of the MR findings in our SDS series suggests a supportive diagnostic role for MR imaging.

Language and speech in a patient with a clinical diagnosis of progressive supranuclear palsy

Language and speech in a patient with a clinical diagnosis of progressive supranuclear palsy

A new meteoric iron from North Carolina

<h3>Objective:</h3> To undertake a systematic review and meta-analysis of studies that investigated prognostic factors and survival in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). <h3>Background:</h3> PSP and MSA are relentlessly progressive neurodegenerative conditions that are associated with a poor prognosis. Numerous primary studies have examined prognostic factors in PSP and MSA but a systematic review or meta-analysis has not been undertaken previously. <h3>Design/Methods:</h3> Publications of at least 10 patients with a likely or confirmed diagnosis of PSP or MSA were eligible for inclusion. Methodological quality was rated using a modified version of the Quality in Prognostic Studies tool. For frequently examined prognostic factors, hazard ratios (HR) derived by univariate and multivariate analysis were pooled in separate subgroups; other results were synthesised narratively and HRs could not be reported here. <h3>Results:</h3> Thirty-seven studies presenting findings on 6257 patients (1911 PSP, 4346 MSA) fulfilled the inclusion criteria. We identified the following variables as unfavourable predictors of survival: In PSP: PSP-Richardson’s phenotype (univariate HR: 2.53; 95%CIs: 1.69, 3.78), early dysphagia and early cognitive symptoms. In MSA: severe dysautonomia and early development of combined autonomic and motor features. In PSP and MSA: early falls (multivariate HR: 2.32; 95%CIs: 1.94, 2.77), the NNIPPS Parkinson plus score and the Clinical Global Impression disease severity score. Sex (multivariate HR: 0.93; 95%CIs: 0.67, 1.28) and MSA phenotype (multivariate HR: 1.22; 95%CIs: 0.83, 1.80) did not predict survival and there was conflicting evidence regarding the prognostic effect of age at disease onset. <h3>Conclusions:</h3> Several clinical variables were strongly associated with shorter survival in PSP and MSA. Results on most prognostic factors were consistent across methodologically diverse studies; however, the lack of commonality of prognostic factors investigated is a significant limitation. <b>Disclosure:</b> Dr. Glasmacher has nothing to disclose. Dr. Leigh has received personal compensation for activities with GSK and Biogen Idec as an advisory board member. Dr. Saha has nothing to disclose.