Effect of aging on magnetic resonance measures differentiating progressive supranuclear palsy from Parkinson's disease

Imaging measurements, such as the ratio of the midsagittal areas of the midbrain and pons (midbrain/pons) and the Magnetic Resonance Parkinsonism Index (MRPI), have been proposed to differentiate progressive supranuclear palsy (PSP) from Parkinson's disease (PD). However, abnormal midbrain/pons values suggestive of PSP have also been reported in elderly individuals and in patients with PD. We investigated the effect of aging on single or combined imaging measurements of the brainstem. We calculated the midbrain/pons and the MRPI (the ratio of the midsagittal areas of the pons and the midbrain multiplied by the ratio of the middle cerebellar peduncle and superior cerebellar peduncle widths) in 152 patients affected by PD, 25 patients with PSP, and a group of 81 age‐matched and sex‐matched healthy controls using a 3‐Tesla magnetic resonance imaging scanner. In healthy controls, aging was negatively correlated with midsagittal area of the midbrain and midbrain/pons values. In patients with PD, in addition to the effect of aging, the disease status further influenced the midbrain/pons values (R² = 0.23; P < 0.001). In both groups, MRPI values were not influenced either by aging or by disease status. No effect of aging on either midbrain/pons or MRPI values was shown in the patients with PSP. Our findings indicated that the MRPI was not significantly influenced by aging or disease‐related changes occurring in PD; whereas, in contrast, the midbrain/pons was influenced. Therefore, the MRPI appears to be a more reliable imaging measurement compared with midbrain/pons values for differentiating PSP from PD and controls in an elderly population. © 2014 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.     

Magnetic resonance imaging in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a tauopathy, presenting clinically most often with a symmetrical akinetic-rigid syndrome, postural instability, supranuclear gaze palsy and frontal dementia. In the absence of reliably validated biomarkers, the diagnosis of PSP in vivo is presently based on clinical criteria, which to date do not include supporting imaging findings, as is accepted for other neurodegenerative diseases. However, data from conventional magnetic resonance imaging (MRI) and various advanced MRI techniques including magnetic resonance volumetry, voxel-based morphometry, diffusion-weighted and diffusion-tensor imaging, magnetization transfer imaging and proton resonance spectroscopy suggest that MRI can contribute valuable information for the differential diagnosis of PSP. We review here the presently published literature concerning MRI in PSP and discuss the potential role of MRI in differentiating PSP from other parkinsonian syndromes.     

PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson's disease

OBJECTIVE: To differentiate the patterns of dopamine transporter loss between idiopathic PD and progressive supranuclear palsy (PSP). METHODS: We used the radiotracer [11C]-WIN 35,428 and PET. Regional striatal dopamine transporter binding was measured in the caudate, anterior putamen, and posterior putamen of six patients with L-dopa-responsive stage 2 PD, six patients with PSP, and six age-comparable healthy controls. RESULTS: In patients with idiopathic PD, the most marked abnormality was observed in the posterior putamen (77% reduction), whereas transporter density in the anterior putamen (60% reduction) and the caudate (44% reduction) was less affected. Unlike the patients with PD, the PSP group showed a relatively uniform degree of involvement in the caudate (40% reduction), anterior putamen (47% reduction), and posterior putamen (51% reduction). When posterior putamen/caudate ratios were calculated, these values were significantly lower in patients with PD than they were in patients with PSP (p = 0.0008) and the control group (p < 0.0001). CONCLUSIONS: Patients with PD have a more pronounced loss of dopamine transporters in the posterior putamen due to a subdivisional involvement of nigrostriatal dopaminergic projections in idiopathic PD. This technique is useful in the determination of neurochemical changes underlying PD and PSP, thus differentiating between them.     

Proton magnetic resonance spectroscopy in Parkinson''s disease and progressive supranuclear palsy.

OBJECTIVES: Proton magnetic resonance spectroscopy (1H-MRS) localised to the lentiform nucleus, was carried out in eight patients with idiopathic Parkinson's disease and five patients with progressive supranuclear palsy. The aim of the study was to assess the concentration of N-acetyl-aspartate (NAA), creatine and phosphocreatine (Cr), and choline containing compounds (Cho) in the putamen and globus pallidus of these patients. METHODS: Peak ratios obtained from patients were compared with those from nine healthy age matched controls. RESULTS: NAA/Cho and NAA/Cr ratios were reduced significantly in patients with progressive supranuclear palsy. CONCLUSION: These results suggest an NAA deficit, due to neuronal loss, in the lentiform nucleus of these patients. 1H-MRS is a non-invasive technique that can provide useful information concerning striatal neuronal loss in the basal ganglia of patients with parkinsonian syndromes.     

Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy

Conventional magnetic resonance imaging (cMRI) is often used to aid the diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), but its ability to predict the histopathological diagnosis has not been systematically studied. cMRI from 48 neuropathologically confirmed cases, including PSP (n = 22), MSA (n = 13), Parkinson's disease (PD) (n = 7), and corticobasal degeneration (n = 6), and controls (n = 9) were assessed blinded to clinical details and systematically rated for reported abnormalities. Clinical diagnosis and macroscopic postmortem findings were retrospectively assessed. Radiological assessment of MRI was correct in 16 of 22 (72.7%) PSP cases and 10 of 13 (76.9%) MSA cases with substantial interrater agreement (Cohen's kappa 0.708; P < .001); no PSP case was misclassified as MSA or vice versa. MRI was less sensitive but more specific than clinical diagnosis in PSP and both more sensitive and specific than clinical diagnosis in MSA. The “hummingbird” and “morning glory” signs were highly specific for PSP, and “the middle cerebellar peduncle sign” and “hot cross bun” for MSA, but sensitivity was lower (up to 68.4%) and characteristic findings may not be present even at autopsy. cMRI, clinical diagnosis, and macroscopic examination at postmortem have similar sensitivity and specificity in predicting a neuropathological diagnosis. We have validated specific radiological signs in pathologically confirmed PSP and MSA. However, the low sensitivity of these and macroscopic findings at autopsy suggest a need for imaging techniques sensitive to microstructural abnormalities without regional atrophy. © 2012 Movement Disorder Society     

Neuropsychiatric symptoms of patients with progressive supranuclear palsy and Parkinson's disease

Neuropsychiatric symptoms are common in basal ganglia disorders and may have severe clinical consequences. The authors compared the neuropsychiatric manifestations of patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP). All 103 PD patients and 27 of the 61 PSP patients were taking dopaminergic agents. PSP patients showed significantly more apathy and disinhibition. Patients with PD had higher frequency of hallucinations, delusions, and depression. These results suggest that PSP patients show symptoms compatible with lesioned orbitofrontal and medial frontal circuits, such as disinhibition and apathy, whereas PD patients show symptoms associated with monoaminergic disturbances, such as psychosis and depression.     

Assessment of midbrain atrophy in patients with progressive supranuclear palsy with routine magnetic resonance imaging

OBJECTIVES: To assess midbrain atrophy through morphometric (linear, surface and volumetric) measurements in patients with clinically diagnosed progressive supranuclear palsy (PSP) and to establish the most accurate measure to be implemented in routine magnetic resonance (MR) protocol in distinguishing PSP from healthy subjects and MSA-p (multiple system atrophy, parkinsonian form) patients. MATERIALS AND METHODS: We studied 15 patients with the diagnosis of probable PSP, seven patients with the diagnosis of probable MSA-p and 14 age-matched healthy volunteers. MR protocol includes a sagittal SE T1-weighted sequence for cross-sectional area and linear brainstem measurements and a 3D-FSPGR sequence for brainstem volume measurements. RESULTS: A highly significant difference in the antero-posterior midbrain diameter, area and volume in PSP compared with control subjects was found. Only a measurement of the midbrain area and pons area enabled one to distinguish between PSP and MSA-p. Receiver operating characteristic analysis revealed that the midbrain area has the highest diagnostic accuracy in distinguishing between PSP and other conditions, with a sensitivity of 100% and specificity of 90.5%. The addition of the midbrain area/pons area ratio (A(ms)/A(pn) ratio) measurement improves the specificity in distinguishing between PSP and MSA. CONCLUSIONS: Morphological indexes indicate midbrain atrophy in PSP patients The combination of the A(ms) and A(ms)/A(pn) ratio measurements allows to discriminate between PSP and other conditions.     

Cognitive and magnetic resonance imaging aspects of corticobasal degeneration and progressive supranuclear palsy.

OBJECTIVE: To identify cognitive and MRI features important for the clinical diagnosis of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP); these diseases share several clinical features and are often difficult to distinguish on clinical grounds. METHODS: Cognitive functions and MRI characteristics were examined in 16 patients with CBD and 28 patients with PSP, all diagnosed according to current clinical criteria (none was examined by autopsy). RESULTS: MRI findings differed significantly between the two groups: 87.5% of patients with CBD but none with PSP had asymmetric frontoparietal atrophy, whereas 89.3% of patients with PSP but only 6.3% of those with CBD had midbrain atrophy. Cognitive examination showed that ideomotor apraxia (De Renzi's test) was significantly more frequent in CBD, and executive functions (Nelson's test) were significantly more impaired in patients with PSP. CONCLUSIONS: MRI findings of asymmetric frontoparietal atrophy in CBD and midbrain atrophy in PSP are the most consistent and useful aids to careful clinical evaluation for differentiating between the two diseases.     

Brain iron in progressive supranuclear palsy: clinical, magnetic resonance imaging, and neuropathological findings

A patient with progressive supranuclear palsy demonstrated a region-specific decrease in T2 signal during high-field-strength brain magnetic resonance imaging. At autopsy the T2-signal hypointensity was found to correspond topographically to increased deposition of ferric iron. The potential clinical, radiologic, and pathophysiologic implications of these findings are discussed.     

Brain iron deposition fingerprints in Parkinson's disease and progressive supranuclear palsy

It can be difficult to clinically distinguish between classical Parkinson's disease (PD) and progressive supranuclear palsy. Previously, there have been no biomarkers that reliably allow this distinction to be made. We report that an abnormal brain iron accumulation is a marker for ongoing neurodegeneration in both conditions, but the conditions differ with respect to the anatomical distribution of these accumulations. We analyzed quantitative T2' maps as markers of regional brain iron content from PD and progressive supranuclear palsy patients and compared them to age-matched control subjects. T2-weighted and T2*-weighted images were acquired in 30 PD patients, 12 progressive supranuclear palsy patients, and 24 control subjects at 1.5 Tesla. Mean T2' values were determined in regions-of-interest in the basal ganglia, thalamus, and white matter within each hemisphere. The main findings were shortened T2' values in the caudate nucleus, globus pallidus, and putamen in progressive supranuclear palsy compared to PD patients and controls. A stepwise linear discriminant analysis allowed progressive supranuclear palsy patients to be distinguished from PD patients and the healthy controls. All progressive supranuclear palsy patients were correctly classified. No progressive supranuclear palsy patient was classified as a healthy control, no healthy controls were incorrectly classified as having progressive supranuclear palsy, and only 6.7% of the PD patients were incorrectly classified as progressive supranuclear palsy. Regional decreases of T2' relaxation times in parts of the basal ganglia reflecting increased brain iron load in these areas are characteristic for progressive supranuclear palsy but not PD patients.     

Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple-system atrophy (MSA-P) may present with a similar phenotype. Magnetic resonance diffusion-weighted imaging (DWI) has been shown to be a sensitive discriminator of MSA-P from Parkinson's disease (PD). We studied 20 PSP, 11 MSA-P, 12 PD patients and 7 healthy controls in order to investigate whether regional apparent diffusion coefficients (rADCs) help distinguish PSP and MSA-P; whether rADCs are correlated with clinical disease severity scores; and the relationship between brainstem and cerebellar volumes and rADCs in PSP and MSA-P. The Unified Parkinson's Disease Rating Scale, Hoehn and Yahr score, Mini Mental State Examination, and frontal assessment battery were recorded in all patients. Regional ADCs were measured in the middle cerebellar peduncle (MCP), caudal and rostral pons, midbrain, decussating fibers of the superior cerebellar peduncle, thalamus, putamen, globus pallidus, caudate nucleus, corpus callosum, frontal and parietal white matter, as well as the centrum semiovale. In MSA-P, rADCs in the MCP and rostral pons were significantly greater than in PSP (P < 0.001 and 0.009) and PD (P < 0.001 and = 0.002). Stepwise logistic regression revealed that the MCP rADC distinguishes MSA-P from PSP with a sensitivity of 91% and a specificity of 84%. Increased brainstem rADCs were associated with motor deficit in MSA-P and PSP. Increased rADCs in the pons and MCP were associated with smaller pontine and cerebellar volumes in MSA-P. rADCs distinguish MSA-P from PSP. These have a clinical correlate and are associated with reduced brainstem and cerebellar volumes.     

Quantitative magnetic resonance spectroscopic imaging in Parkinson’s disease,progressive supranuclear palsy and multiple system atrophy

Background and purpose: Magnetic resonance spectroscopy (MRS) allows the measurement of a number of brain tissue metabolites in vivo, including N‐acetylaspartate (NAA), a putative marker of neuronal integrity. Unlike single voxel MRS, magnetic resonance spectroscopic imaging (MRSI) enables quantification of these metabolites simultaneously from multiple anatomically localized voxels. Both single voxel MRS and MRSI allow the absolute quantification of these metabolites and, when combined with tissue segmentation, can give accurate metabolite concentrations even in the presence of partial volume effects from nearby cerebrospinal fluid. Methods: Using MRSI with cubic voxels with a nominal volume of 1.0 cm³, we tested the hypothesis that concentrations of NAA in the basal ganglia in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) would show differences compared to Parkinson’s disease (IPD). NAA values (in mM) from MRSI voxels centred to the putamen, pallidum and thalamus were obtained from 11 patients with IPD, 11 with MSA‐P, six with MSA‐C, 13 with PSP and 18 controls. The mean concentrations of NAA and its bulk grey and white matter values were also estimated over the whole brain slab. Results: N‐acetylaspartate concentrations in the pallidum, putamen and lentiform nucleus were significantly lower in patients with MSA‐P and PSP compared to IPD and controls. The putaminal values were also significantly reduced in PSP compared to MSA‐P. There were no significant differences between groups in the thalamus and over the whole brain slab. Conclusion: Our findings support the notion that MRSI can potentially quantify basal ganglia cellular pathology in MSA and PSP.     

Controlled trial of pergolide mesylate in Parkinson's disease and progressive supranuclear palsy

We evaluated pergolide in 22 patients with Parkinson's disease and 3 with progressive supranuclear palsy (PSP). After achieving an optimal dose of pergolide and Sinemet, a matching placebo was substituted in double-blind manner. The mean dose of levodopa (in Sinemet) was reduced by 68%; in eight patients, pergolide completely replaced levodopa. In parkinsonian patients, the mean Hoehn-Yahr stage decreased from 3.2 to 1.6, and the mean total disability score decreased from 48.3 to 17.8. In 10 patients with on-off phenomenon, the time on increased 174% with pergolide. There was little effect in PSP. Postural light-headedness and reversible mental changes were seen.     

Magnetic resonance imaging distinguishes progressive supranuclear palsy from multiple system atrophy

Summary. To establish diagnostic magnetic resonance imaging (MRI) criteria for differentiating progressive supranuclear palsy (PSP) from multiple system atrophy (MSA), magnetic resonance images from eight patients with probable PSP, 30 with probable MSA {nine striatonigral degeneration (MSA-P) and 21 olivopontocerebellar atrophy (MSA-C)}, and ten age-matched controls were retrospectively studied. Anteroposterior diameters in the midline sagittal T1-weighted image of the rostral (RMT) and caudal midbrain tegmentum (CMT), caudal pons and medulla were measured. Divergence of the red nuclei (RN) in the axial T2-weighted image was judged. All PSP images had a smaller RMT diameter than the lower limit of the normal range, showed RN divergence, and had a pontine diameter within the normal range. All MSA images had a CMT diameter within the normal range; no MSA images showed divergence of RN. Forty-four percent (4/9) of MSA-P and 76% (16/21) of MSA-C images had a pontine diameter smaller than the lower limit of the normal range. On basis of the results, we propose MRI diagnostic criteria for differentiating PSP from MSA. Received March 23, 2000; accepted June 7, 2000