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Published online before print November 8, 2007, 10.1148/radiol.2453061703
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(Radiology 2008;246:214-221.)
© RSNA, 2007

Neuroradiology

MR Imaging Index for Differentiation of Progressive Supranuclear Palsy from Parkinson Disease and the Parkinson Variant of Multiple System Atrophy1

Aldo Quattrone, MD, Giuseppe Nicoletti, MD, Demetrio Messina, MD, Francesco Fera, MD, Francesca Condino, PhD, Pierfrancesco Pugliese, MD, Pierluigi Lanza, MD, Paolo Barone, MD, Letterio Morgante, MD, Mario Zappia, MD, Umberto Aguglia, MD, and Olivier Gallo, STc

1 From the Institute of Neurology (A.Q., D.M., P.P.) and Neuroradiology (F.F.), Magna Graecia University of Catanzaro, Catanzaro, Calabria, Italy; Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, Calabria, Italy (A.Q., G.N., F.C., P.L., O.G.); Department of Neurological Sciences, University of Naples Federico II, Naples, Italy (P.B.); Department of Neuroscience, Psychiatry and Anesthesiology, University of Messina, Messina, Sicily (L.M.); Institute of Neurology, Department of Neurosciences, University of Catania, Catania, Sicily (M.Z.); and Regional Epilepsy Center, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio di Calabria, Calabria, Italy (U.A.). Received October 2, 2006; revision requested December 12; revision received January 17, 2007; accepted February 28; final version accepted April 16. Address correspondence to A.Q., Clinica Neurologica, Policlinico Mater Domini, Campus Universitario, Germaneto, 88100 Catanzaro, Italy (e-mail: a.quattrone{at}isn.cnr.it).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To prospectively assess sensitivity and specificity of magnetic resonance (MR) imaging measurements of midbrain, pons, middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) for differentiating progressive supranuclear palsy (PSP) from Parkinson disease (PD) and Parkinson variant of multiple system atrophy (MSA-P), with established consensus criteria as reference standard.

Materials and Methods:All study participants provided informed consent; study was approved by the institutional review board. Pons area, midbrain area, MCP width, and SCP width were measured in 33 consecutive patients with PSP (16 possible, 17 probable), 108 consecutive patients with PD, 19 consecutive patients with MSA-P, and 50 healthy control participants on T1-weighted MR images. The pons area–midbrain area ratio (P/M) and MCP width–SCP width ratio (MCP/SCP) were also used, and an index termed MR parkinsonism index was calculated [(P/M)·(MCP/SCP)]. Differences in MR imaging measurements among groups were evaluated with Kruskal-Wallis test, Mann-Whitney U test, and Bonferroni correction.

Results:Midbrain area and SCP width in patients with PSP (23 men, 10 women; mean age, 69.3 years) were significantly (P < .001) smaller than in patients with PD (62 men, 46 women; mean age, 65.8 years), patients with MSA-P (five men, 14 women; mean age, 64.0 years), and control participants (25 men, 25 women; mean age, 66.6 years). P/M and MCP/SCP were significantly larger in patients with PSP than in patients in other groups and control participants. All measurements showed some overlap of values between patients with PSP and patients from other groups and control participants. MR parkinsonism index value was significantly larger in patients with PSP (median, 19.42) than in patients with PD (median, 9.40; P < .001), patients with MSA-P (median, 6.53; P < .001), and control participants (median, 9.21; P < .001), without overlap of values among groups. No patient with PSP received a misdiagnosis when the index was used (sensitivity and specificity, 100%).

Conclusion: The MR parkinsonism index can help distinguish patients with PSP from those with PD and MSA-P on an individual basis.

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by supranuclear vertical gaze palsy, postural instability and falls, parkinsonian features, speech disturbance, and cognitive impairment (1–3). Clinically differentiating PSP from Parkinson disease (PD) and multiple system atrophy (MSA) may be challenging, especially in the first stages of the disease. Magnetic resonance (MR) imaging has been widely used to differentiate atypical parkinsonian syndromes from PD. Studies with routine MR imaging (4–8), MR spectroscopy (9–11), diffusion-weighted MR imaging (12,13), and volumetric MR imaging (14,15) have proved to be useful in distinguishing PD from PSP and MSA, but some overlap of MR imaging findings makes neuroimaging for differentiation of patients with distinct parkinsonian disorders still inaccurate on an individual basis.

Pathologic findings and MR imaging evidence indicate that the midbrain and the superior cerebellar peduncles (SCPs) are atrophic in PSP (1,4,15–18), whereas the middle cerebellar peduncles (MCPs) and the pons are mainly involved in MSA (4,8,18–20). By contrast, all these brain structures are spared in PD. Thus, the purpose of our study was to prospectively assess the sensitivity and specificity of single and combined MR imaging measurements of brain structures (midbrain, pons, MCP, and SCP) for differentiating PSP from PD and the Parkinson variant of MSA (MSA-P), by using established consensus criteria as the reference standard.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Patients, Control Participants, and Reference Standard
From June 2002 to May 2006, 33 consecutive patients with PSP (16 possible and 17 probable), 108 consecutive patients with PD, 19 consecutive patients with MSA-P, and 50 age-matched healthy participants were examined. Clinical diagnosis of PSP, PD, and MSA-P was determined by one of the authors (G.N., with more than 10 years of experience in movement disorders) according to established consensus criteria (21–23). The patients were included in the study only when they fulfilled the proposed criteria for possible or probable PSP (22), a diagnosis of PD (21), and probable MSA-P (24). All patients were evaluated clinically and examined with MR imaging. In patients with PD, the levodopa response was considered positive when the clinical improvement was 30% or greater according to results of the acute levodopa test (the test with administration of a single dose of levodopa). In MSA-P and PSP, a self-reported sustained improvement coincident with the introduction of levodopa was considered to be a positive response. None of the healthy control participants had a history of central nervous system diseases, and all of them had normal results at neurologic examination. All control participants underwent brain MR imaging. All study participants provided informed consent for participation in the study, which was approved by the institutional review board.

MR Imaging Protocol
MR imaging was performed by using a 1.5-T imager (Signa NV/I; GE Medical Systems, Milwaukee, Wis). All MR imaging examinations included transverse intermediate-weighted and T2-weighted dual-echo fast spin-echo (repetition time msec/echo time msec, 3500/10.2, 85; section thickness, 4 mm; frequency- and phase-encoding matrix, 288 x 224), transverse fluid-attenuated inversion-recovery (repetition time msec/echo time msec/inversion time msec, 8000/120/2000; section thickness, 4 mm; frequency- and phase-encoding matrix, 256 x 224), transverse T2-weighted gradient-echo (500/15; section thickness, 4 mm; frequency- and phase-encoding matrix, 256 x 192; flip angle, 20°), and T1-weighted volumetric spoiled gradient-echo (15.2/6.8; section thickness, 0.6 mm; frequency- and phase-encoding matrix, 256 x 256; flip angle, 15°) sequences. An off-line resectioning procedure (multiplanar reconstruction program [GE Medical Systems, Milwaukee, Wis]) was used to expose high-spatial-resolution views of SCPs. A volumetric slab of 45 mm (0.9-mm section thickness) tangent to the floor of the fourth ventricle was placed on a midsagittal plane to cover the entire extension of SCPs. The resulting oblique coronal images were used for subsequent SCP width quantification, as discussed next.

Image Analysis
Two independent raters (F.F. and D.M.) who were blinded to the patients' diagnoses evaluated all MR images. To assess the intrarater reliability, a second evaluation was made 2 weeks after the first evaluation by one of the two raters (D.M.), who assigned scores to all images and who was blinded as before.

Conventional transverse brain MR images were visually inspected for the presence or absence of putaminal atrophy, putaminal hypointensity, slitlike hyperintensity in the posterolateral margin of the putamen, brainstem atrophy, hyperintensity of the MCPs, and cruciform hyperintensity of the pons. Cruciform hyperintensity was considered as present if it was unequivocal on T2-weighted and intermediate-weighted MR images. On midsagittal T1-weighted MR images, the presence of the penguin silhouette sign (atrophy of the midbrain tegmentum and the normal pons looking like a lateral view of a standing penguin with a small head and a big body) described by Oba et al (25) was considered suggestive of marked midbrain atrophy. The midbrain area and pons area were measured on midsagittal T1-weighted volumetric spoiled gradient-echo MR images in all patients and healthy control participants as described by Oba et al (25). A line passing through the superior pontine notch and the inferior edge of the quadrigeminal plate was drawn (line A). A second line parallel to the first line passing through the inferior pontine notch was also drawn (line B). The midbrain area was traced around the edges of line A and the midbrain tegmentum above it. The pons area was included between the lines along the anterior and posterior margins of the pons and lines A and B. Measurement of MCP width was performed on T1-weighted volumetric spoiled gradient-echo MR images, as previously described (20).

The midsagittal section of the brain MR image was chosen as the reference starting view. Left and right MCPs were identified on parasagittal views that best exposed the MCP between the pons and the cerebellum. The linear distance between the superior and inferior borders of the MCP, as delimited by the peripeduncular cerebrospinal fluid spaces of the pontocerebellar cisterns, was measured. Each MCP width (left and right) was measured, and a mean value for the two MCPs was calculated. SCPs were measured on the T1-weighted volumetric spoiled gradient-echo high-spatial-resolution oblique coronal MR images previously generated. Images were visually inspected in the anteroposterior direction to identify the first view on which inferior colliculi and SCPs were separated. This image was used as the starting view for SCP measurements, which were always performed on three consecutive sections. Measurements were obtained by averaging measurements of the linear distance between the medial and lateral borders of both SCPs at the middle of their extension. The pons area–midbrain area ratio (P/M) and MCP width–SCP width ratio (MCP/SCP) were also used, and an index that we termed the MR parkinsonism index was calculated [(P/M)·(MCP/SCP)].

Statistical Analysis
The difference in sex distribution among groups was evaluated with the {chi}2 test, followed by evaluation with the pairwise test for comparison of two proportions, corrected according to the Bonferroni method. Evaluation with one-way analysis of variance, followed by that with the unpaired t test and Bonferroni correction, was performed to compare age at examination, disease duration, and age at onset. To assess the differences in Hoehn-Yahr scores and MR image measurements among groups, the Kruskal-Wallis test was used, followed by evaluation with the Mann-Whitney U test for multiple comparisons. Resulting P values were corrected according to the Bonferroni method. To verify the agreement between the two raters and the intrarater reliability, the intraclass correlation coefficient was calculated. The Spearman coefficient was calculated to test correlations between MR image measurements and demographic or clinical variables. Sensitivity, specificity, and positive predictive value (PPV) were determined for differentiating patients with PSP from patients with MSA-P, for differentiating patients with PSP from patients with PD, and for differentiating patients with PSP from control participants. These values were calculated by using the optimal cutoff values determined by using receiver operating characteristic curve analysis. The optimal cutoff level was considered the value that had the highest sum of sensitivity and specificity values. All tests were two tailed, and the {alpha} level was set at P < .05.

Statistical analysis was performed with statistical software (SPSS for Windows, version 12.0; SPSS, Chicago, Ill).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
Patients
A flow diagram of our study is shown in Figure 1. Demographic and clinical data of patients and control participants are shown in Table 1. All patients with PD had a positive response to levodopa, whereas only six of 19 patients with MSA-P and four of 33 patients with PSP had a transient positive levodopa response. None of the patients with MSA-P had ataxia or other cerebellar signs at the onset of the disease.


Figure 1
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  		Figure 1: Flow diagram of our study. Eligible participants were patients suspected of having PSP, PD, or MSA-P or healthy control participants. Clinical evaluation was performed by using established consensus criteria for PSP as the reference standard. The MR parkinsonism index (MRPI) value was considered abnormal when the values were equal to or higher than the cutoff levels calculated for patients with PD, patients with MSA-P, and healthy control participants (patients with PSP vs patients with PD, ≥13.55; patients with PSP vs patients with MSA-P, ≥12.85; patients with PSP vs control participants, ≥13.58). The group of patients with PSP includes those with possible PSP and probable PSP.

 

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  		Table 1. Demographic and Clinical Data in Patients with PSP, MSA-P, and PD and in Control Participants

 
Imaging Features
MR images in the patients with PSP showed that marked atrophy of the midbrain (median area, 61.0 mm2; range, 38–68 mm2) was present in most patients (23 of 33), whereas those in patients with MSA-P showed that at least one of the features commonly described in this disease was present (4,6–8). Among 19 patients with MSA-P, five had cruciform hyperintensity, 13 had slitlike hyperintensity of the posterolateral margin of the putamen, six had atrophy of the putamen, nine had putaminal hypointensity, nine had atrophy of the pons, and two had hyperintensity of the MCPs. Among 108 patients with PD, only eight had slitlike hyperintensity of the posterolateral margin of the putamen, and three had putaminal hypointensity. No control participants had abnormalities on brain MR images.

Measurements of Single Brain Structures
Measurements of the midbrain area, pons area, MCP width, and SCP width are shown in Figure 2. Measurements for midbrain area and SCP width (Table 2) were significantly smaller in patients with PSP than in patients with PD, patients with MSA-P, and control participants (Table 3). In patients with PSP, there was a significant difference between patients with possible PSP (midbrain area: median, 69 mm2; range, 61–94 mm2; SCP width: median, 2.72 mm; range, 1.80–3.25 mm) and patients with probable PSP (midbrain area: median, 54 mm2; range, 38–91 mm2; SCP width: median, 1.80 mm; range, 1.62–2.05 mm), with smaller values observed in the latter patients (P = .003 and P < .001, respectively). Measurements for pons area and MCP width were smaller in patients with MSA-P than in patients in the other groups (Tables 2 and 3). No difference between patients with PD and control participants was observed for any measurement. For each measurement, the range of the values was not different between men and women in all the groups.


Figure 2A
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  		Figure 2a: Sagittal and coronal T1-weighted volumetric spoiled gradient-echo MR images (15.2/6.8; section thickness, 0.6 mm; frequency- and phase-encoding matrix, 256 x 256; flip angle, 15°) show midbrain area (1), pons area (2), MCP width (3), and SCP width (4) in (a) a control participant and (b) a patient with PSP. Images show marked atrophy of both midbrain and SCP in the PSP patient in comparison with the healthy control participant. In the patient with PSP, values were as follows: midbrain area, 60 mm2; pons area, 502 mm2; MCP width, 8.15 mm; and SCP width, 1.70 mm. In the control participant, values were as follows: midbrain area, 108 mm2; pons area, 478 mm2; MCP width, 10.05 mm; and SCP width, 4.10 mm.

 

Figure 2B
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  		Figure 2b: Sagittal and coronal T1-weighted volumetric spoiled gradient-echo MR images (15.2/6.8; section thickness, 0.6 mm; frequency- and phase-encoding matrix, 256 x 256; flip angle, 15°) show midbrain area (1), pons area (2), MCP width (3), and SCP width (4) in (a) a control participant and (b) a patient with PSP. Images show marked atrophy of both midbrain and SCP in the PSP patient in comparison with the healthy control participant. In the patient with PSP, values were as follows: midbrain area, 60 mm2; pons area, 502 mm2; MCP width, 8.15 mm; and SCP width, 1.70 mm. In the control participant, values were as follows: midbrain area, 108 mm2; pons area, 478 mm2; MCP width, 10.05 mm; and SCP width, 4.10 mm.

 

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  		Table 2. Measurements for Brain Structures in Patients with PSP, MSA-P, and PD and Control Participants

 

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  		Table 3. Pairwise Comparisons between Groups

 
Combined Assessment of Brain Structures
P/M values.—The value for P/M in patients with PSP (median, 6.67; range, 4.35–9.09) was significantly larger than that observed in patients with MSA-P (median, 3.22; range, 2.17–5.26; P < .001) and with PD (median, 4.0; range, 2.94–6.25; P < .001) and in control participants (median, 3.85; range, 2.78–5.56; P < .001). However, patients with PSP showed some overlap of individual values with those of patients with MSA-P and PD and of control participants (Fig 3). There was no significant difference between patients with possible PSP and patients with probable PSP. Patients with MSA-P had a significantly smaller P/M than did patients with PD (P < .001) and control participants (P < .0017), but again some overlap of individual values occurred among the groups (Fig 3). No difference was observed between patients with PD and control participants.


Figure 3
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  		Figure 3: Box plots in patients with possible PSP, patients with probable PSP, patients with PD, and patients with MSA-P and in control participants. Vertical solid lines (whiskers) show lower and upper values. Box stretches from lower hinge (25th percentile) to upper hinge (75th percentile). Median is shown as line across each box. Left: P/M. Middle: MCP/SCP. Right: MR parkinsonism index (MRPI). None of the MR parkinsonism index measurements in both PSP groups overlapped with values in the other groups.

 
Sensitivity, specificity, and PPV of the P/M for differentiating patients with PSP from those with PD, patients with PSP from those with MSA-P, and patients with PSP from control participants varied at different cutoff levels (Table 4), and the optimal levels were 4.88 or greater, 4.62 or greater, and 4.65 or greater, respectively.


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  		Table 4. MR Parkinsonism Index for Differentiation of Patients with PSP from Patients with PD and MSA-P and Control Participants

 
MCP/SCP values.—The value for MCP/SCP in patients with PSP (median, 3.14; range, 2.29–4.79) was significantly larger than that observed in patients with MSA-P (median, 2.00; range, 1.33–2.63; P < .001), patients with PD (median, 2.36; range, 1.78–3.01; P < .001), and control participants (median, 2.38; range, 1.91–2.89; P < .001) (Fig 3), whereas the ratio in patients with MSA-P was smaller than that in patients with PD (P < .001) and in control participants (P < .001) (Fig 3). No difference, however, was observed between patients with PD and control participants. There was some overlap of individual values among all groups (Fig 3). There was no significant difference between patients with possible PSP and patients with probable PSP.

Sensitivity, specificity, and PPV of MCP/SCP for differentiating patients with PSP from those with PD, patients with PSP from those with MSA-P, and patients with PSP from control participants varied at different cutoff levels (Table 4), and the optimal levels were 2.69 or greater, 2.43 or greater, and 2.69 or greater, respectively.

MR parkinsonism index values.—Patients with PSP showed the highest MR parkinsonism index values with respect to all other groups (patients with PSP vs patients with MSA-P, P < .001; patients with PSP vs patients with PD, P < .001; patients with PSP vs control participants, P < .001) (Fig 3). There was no overlap of individual values for the MR parkinsonism index between the patients with PSP (median, 19.42; range, 14.39–40.11) and those with MSA-P (median, 6.53; range, 3.87–11.3), those with PD (median, 9.40; range, 6.33–12.71), and control participants (median, 9.21; range, 6.29–12.77) (Fig 3). In patients with PSP, a significant correlation was found between the MR parkinsonism index value and the duration of the disease (P < .002). Moreover, in patients with PSP, the MR parkinsonism index value was significantly different between those with possible PSP (median, 16.41; range, 14.39–21.44) and those with probable PSP (median, 24.56; range, 16.09–40.11), with higher values observed in the latter patients (P < .001) (Fig 3). In patients with MSA-P, the average MR parkinsonism index value was significantly lower than that measured in patients with PD (P < .001) and control participants (P < .001), but some overlap of the individual MR parkinsonism index values occurred among these groups. There was no difference in the MR parkinsonism index values between patients with PD and control participants.

Sensitivity, specificity, and PPV of the MR parkinsonism index for differentiating patients with PSP from those with PD, patients with PSP from those with MSA-P, and patients with PSP from control participants varied at different cutoff levels (Table 4), and the optimal levels were 13.55 or greater, 12.85 or greater, and 13.58 or greater, respectively.

Statistical Measurements
The intraclass correlation coefficients for intrarater and interrater reliability of the measurement procedures varied from 0.985 to 0.996 and 0.957 to 0.980, respectively (Table 5). Sensitivity, specificity, and PPV of the measurements (P/M, MCP/SCP, and MR parkinsonism index) varied (Table 4). The MR parkinsonism index was the only measurement that showed a sensitivity, specificity, and PPV of 100% for distinguishing patients with PSP from those with MSA-P or PD and control participants.


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  		Table 5. Intra- and Interrater Reliability for Measurements of Brain Structures in Patients with PSP, MSA-P, and PD and Control Participants

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 
In our study, we measured some brain structures mainly involved in PSP and other atypical forms of parkinsonism to differentiate patients with PSP from those with PD and MSA-P. Atrophy of the midbrain is the characteristic pathologic finding in patients with PSP (1,16,26). Findings of MR imaging (25,27) confirmed the diagnostic value of the presence of midbrain atrophy in patients with PSP and suggested that the measurement of the midbrain area could help in the differentiation of patients with PSP from those with PD. Our findings, however, demonstrate that the measurement of the midbrain area on MR images failed to aid in the differentiation, on an individual basis, of patients with PSP from those of all other groups. In our series of patients, the average midbrain area of patients with PSP was significantly smaller than that of patients with MSA-P, patients with PD, and control participants, but individual values of the midbrain area measured in patients with PSP overlapped with those values from other groups of patients.

Our findings are in agreement with those of a recent report (28) in which the midbrain area values measured in patients with PSP overlapped with those measured in control participants. Recently, some authors (25) reported that the P/M was a better measurement for differentiation of patients with atypical parkinsonian syndromes from those with PD and control participants. In our series, the use of this ratio, as well as that of the measurement of midbrain area, did not allow us to distinguish, on an individual basis, patients with PSP from patients with PD, patients with MSA-P, and control participants. We cannot explain the reason for this discrepancy. We believe that the sample size investigated in our study, a size that was larger than that reported in previously published studies, may account for these contradictory results. Some authors (28) recently demonstrated that 6% of patients with PSP had a P/M that overlapped with the P/M of control participants, a finding that was consistent with our findings.

Pathologic evidence has also demonstrated the atrophy of SCPs in patients with PSP (1,17), whereas atrophy of MCPs has been found in patients with MSA (19). Results in recent MR imaging studies have confirmed these pathologic observations in both diseases. Atrophy of the SCPs has been shown on volumetric MR images in patients with PSP (15), and decreased width of MCPs recently has been demonstrated on midsagittal MR images in patients with MSA (20). On this basis, in our study we measured the width of both SCPs and MCPs on MR images and also investigated the MCP/SCP. Our data confirm pathologic findings showing that the SCP width was significantly smaller in patients with PSP than in those with MSA-P and those with PD or in the control participants, whereas MCP width was smaller in patients with MSA-P in comparison with that in all other groups. In addition, our study also demonstrates that the MCP/SCP was significantly higher in patients with PSP than in those with PD or MSA-P and control participants, but this ratio, as well as the single measurements of the SCP width and MCP width, failed to aid in the distinguishing, on an individual basis, of patients in the PSP group from those of all other groups.

Considering that the sensitivity to predict PSP of the previously mentioned measurements was lower than 100%, we used a combined MR imaging assessment of four brain structures involved in these neurodegenerative diseases (atrophy of the midbrain and SCPs suggests PSP, whereas atrophy of the pons and MCPs suggests MSA-P) to improve differentiation between patients with PSP from those with MSA-P and those with PD. We calculated an index, which we propose to call the MR parkinsonism index, thus: (P/M)·(MCP/SCP). The values obtained by using this calculation in patients with PSP were significantly higher than those obtained in all other groups. Moreover, the MR parkinsonism index values showed no overlap between values of patients with PSP and patients with MSA-P or values of those with PD and control participants, demonstrating that this index allowed differentiation of patients with PSP from patients with PD, patients with MSA-P, and control participants on an individual basis. The MR parkinsonism index allowed discrimination of patients with PSP from those with MSA-P and those with PD and control participants, with a sensitivity of 100%, a specificity of 100%, and a PPV of 100%.

To evaluate whether the MR parkinsonism index also was useful to identify patients with PSP in the early stage of the disease when diagnosis may still be inaccurate, we considered patients with probable PSP and possible PSP separately, because patients with possible PSP rather than patients with probable PSP may be more likely to have other diseases (22). The MR parkinsonism index helped to either differentiate patients with probable PSP from patients with possible PSP or differentiate patients with possible PSP from patients in all other groups. Indeed, no patient with PSP (probable or possible) was misclassified when the MR parkinsonism index was used. In addition, the MR parkinsonism index was strongly related to duration of the disease, a factor that indicated that this index may be a good indicator of the progression of PSP. Taken together, these findings suggest that the MR parkinsonism index also can help distinguish patients in the early stages of PSP, when the clinical picture may resemble that of other neurodegenerative diseases and when PSP is most commonly misdiagnosed as PD or cerebrovascular disease.

There were some limitations to this study. We used clinical criteria for the diagnosis of the diseases, and we did not have pathologic confirmation. Thus, it is possible that in some patients the clinical diagnosis may be in error. However, this seems unlikely because the sensitivity and specificity of the clinical diagnostic criteria that we applied in our patients for PSP, MSA, and PD are high (29), and all patients included in our study were evaluated in a standardized fashion by one of the authors (G.N.) who had more than 10 years of experience in movement disorders. Further, in our study, the same individuals were used to develop the MR parkinsonism index and then to assess its performance, and this factor could have led to exaggeration of the performance of the MR parkinsonism index. A prospective study in a larger cohort of patients is needed to confirm the accuracy of the MR parkinsonism index for the diagnosis of possible PSP and probable PSP.

Our study had several positive aspects. First, the MR parkinsonism index allowed correct classification of all patients with PSP included in our study, and no patient was misclassified as having MSA-P or PD. Second, the MR parkinsonism index was used to correctly classify patients with PSP in the early stages of the disease, when diagnostic errors are most likely to occur. Third, the use of routine MR imaging for calculating the MR parkinsonism index makes this index of particular practical value because the previously mentioned measurements can be easily performed in nonresearch settings as well. In conclusion, our findings indicate that the combined assessment at routine MR imaging of brain structures involved in atypical parkinsonian syndromes is useful for distinguishing patients with PSP from patients with PD, patients with MSA-P, and control participants on an individual basis.


   ADVANCES IN KNOWLEDGE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
IMPLICATION FOR PATIENT CARE
 References
 


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
References
 


   ACKNOWLEDGMENTS
 
We thank Gemma Di Palma, STc, Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, Italy, for her assistance in the recruitment of the patients.


   FOOTNOTES
 

Abbreviations: MCP = middle cerebellar peduncle • MCP/SCP = MCP width–SCP width ratio • MSA = multiple system atrophy • MSA-P = Parkinson variant of MSA • PD = Parkinson disease • P/M = pons area–midbrain area ratio • PPV = positive predictive value • PSP = progressive supranuclear palsy • SCP = superior cerebellar peduncle

Guarantor of integrity of entire study, A.Q.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, A.Q., D.M., F.F., P.P.; clinical studies, G.N., D.M., P.P., P.B., L.M., M.Z., U.A.; statistical analysis, F.C.; and manuscript editing, A.Q., G.N., F.F.

Authors stated no financial relationship to disclose.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
ADVANCES IN KNOWLEDGE
 IMPLICATION FOR PATIENT CARE
 References
 

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