Progressive Supranuclear Palsy Workup

Updated: Oct 17, 2018
  • Author: Eric R Eggenberger, DO, MS, FAAN; Chief Editor: Selim R Benbadis, MD  more...
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Workup

Laboratory Studies

Workup in the setting of suspected progressive supranuclear palsy (PSP) is directed principally at eliminating other diagnoses.

Borroni et al proposed evaluation of tau forms in cerebrospinal fluid (CSF) as a biomarker for PSP. [38] CSF contains both extended (55 kd) and truncated (33 kd) tau forms, and the truncated-to-extended ratio is significantly lower in PSP than in other neurodegenerative disorders. In this study, the ratio was 0.504 ± 0.284 in PSP patients, 0.899-1.215 in patients with other neurodegenerative conditions, and 0.989 ± 0.343 in controls. In addition, a decreased ratio was correlated with brainstem atrophy, as assessed by voxel-based morphometry. Further study of such biomarker candidates is required before these become incorporated into diagnostic algorithms or criteria.

Whipple polymerase chain reaction (PCR) may be helpful in eliminating the possibility of Whipple disease, a treatable infectious disorder.

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Magnetic Resonance Imaging

Although, magnetic resonance imaging (MRI) of the brain offers little help in the early stages of PSP, it may reveal the following abnormalities in some advanced cases [2, 3, 4, 5, 6] :

  • Atrophy of the midbrain (see the image below) with cisternal and ventricular dilatation

  • Thinning of the quadrigeminal plate

  • Dilation of the third ventricle

  • A nonspecific finding of increase in proton density images in the periaqueductal gray matter, compatible with gliotic changes

    Sagittal T1-weighted image shows atrophy of midbra Sagittal T1-weighted image shows atrophy of midbrain, preservation of pontine volume, and atrophy of the tectum, suggestive of progressive supranuclear palsy (Steele-Olszewski-Richardson disease).

Righini et al reported the usefulness of assessing the appearance of the superior profile of the midbrain on midsagittal T1-weighted MRI. [39] The appearance of a flat or concave profile (as opposed to the normal convex profile) was associated with a 68% sensitivity and an 89% specificity for the diagnosis of PSP as compared with the diagnosis of Parkinson disease.

It should be kept in mind that these imaging findings are not pathognomonic of PSP nor early findings; some of their components may be observed in several other diseases in the differential diagnosis.

A study from Hamburg, Germany, reported that an abnormal brain iron accumulation was a marker for ongoing neurodegeneration in both PSP and Parkinson disease, but the 2 conditions differed with respect to the anatomic distribution of this accumulation. The investigators found that regional decreases of T2' relaxation times in parts of the basal ganglia reflecting increased brain iron load were characteristic for progressive supranuclear palsy but not for Parkinson disease. [40]

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Other Neuroimaging

Neuroimaging is often performed to eliminate other entities in the differential diagnosis. The presence of significant abnormalities (eg, large vessel ischemic disease, hydrocephalus) casts doubt on the diagnosis of PSP. Functional neuroimaging includes positron emission tomography (PET) and single-photon emission computed tomography (SPECT).

PET may help reveal physiopathologic aspects of the disease. PET studies have documented a global cerebral hypometabolism with relative selectivity in the frontal cortex. [41, 42, 43] Regional cerebral blood flow and oxygen metabolism are decreased in the caudate and putamen and impaired in the thalamus and brainstem. PET studies have also documented significantly lowered glucose metabolism in the midbrain of PSP patients as compared with control subjects. [44]

Fluorodopa (F-dopa) PET has shown reduced F-dopa influx into the caudate and putamen. In idiopathic Parkinson disease, the caudate is affected less severely; therefore, this finding can help in differentiating the 2 conditions. [45] The costs of PET studies and their limited availability restrict this technique to experimental trials.

In some patients with PSP,123 I-iodobenzamide SPECT has demonstrated reduced striatal dopamine receptor binding. [46] This finding can be used to distinguish vascular white-matter lesions from PSP.

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Sleep Studies

Sleep patterns are often abnormal in individuals with PSP. Polysomnography shows diminished total sleep time, increased awakenings, progressive loss of rapid-eye-movement (REM) sleep, [7, 8] and decreased REM–to–non-REM (NREM) quotient. [9, 10] REM sleep behavior disorder, consisting of motor activity associated with vivid dreams during REM sleep, also occurs in individuals with PSP.

These abnormalities are not specific for PSP. For example, Sixel-Döring et al found that although polysomnographically recorded sleep is more severely impaired in patients with PSP than in patients with Parkinson disease, Parkinson Disease Sleep Scale scores did not differ significantly between the 2 patient groups. [47]

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Histologic Findings

The histopathology of PSP involves diffuse brainstem disease. Neuronal loss, neurofibrillary tangles (NFTs), and gliosis affect the reticular formation and ocular motor nuclei. Early pathology is evident primarily in the midbrain; this may explain the early vertical eye movement characteristics. The pontine nucleus raphe interpositus and pedunculopontine and deep pontine nuclei are also affected.

The distribution and ultrastructure of NFTs in PSP are distinct from those of NFTs in Alzheimer disease. PSP is characterized by greater subcortical involvement, with single tubules 15-20 nm wide, whereas Alzheimer disease is characterized by cortically based paired helicoid filaments.

An examination of PSP cases revealed the uniform presence of tau-positive cortical lesions. These were found in highest concentration in the precentral and angular gyrus, primarily affecting the deep cortical layers, and involved both small and large neurons. Again, this pattern differs from the NFT pattern observed in Alzheimer disease. NFT concentration analysis appeared to implicate the pedunculopontine nucleus in lesion spread.

Although NFTs are the histologic hallmarks of PSP, neuropil threads have also been found extensively.

Besides the brainstem structures, the striatum, the medial pallidum, the subthalamic nucleus, and the substantia nigra are also affected.

There remain many unanswered questions about the pathologic features linking PSP, Alzheimer disease, idiopathic Parkinson disease, and, in particular, corticobasal degeneration. Further ultrastructural and genetic studies are needed to reveal the cause and the pathogenesis of the disease.

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