Review Article

Brain MR Contribution to the Differential Diagnosis of Parkinsonian Syndromes: An Update

Table 2

Studies evaluating quantitative advanced brain MR parameters for the differential diagnosis between Parkinson’s disease and atypical parkinsonisms.

Author, yearMagnetic fieldTechniqueCohortResultsAcc/Se/Sp

Kato et al., 2003 [46]1.5 TMorphometric measurementsPSP = 8; PD = 12; HC = 10
DD (y, M ± SD): PSP = 6.4 ± 6.2; PD = 6.9 ± 7.2
↓ area of midbrain tegmentum, inferior colliculus, and pontine tegmentum in PSP versus PDNot reported

Oba et al., 2005 [47]1.5 TMorphometric measurementsPSP = 21; MSA-P = 25; PD = 23; HC = 31
DD (y, M ± SD): PSP = 2.8 ± 1.3; MSA-P = 7.8 ± 3.8; PD = 6.6 ± 1.9
↓ midbrain area in PSP versus PD and MSA-P
↓ pons area in MSA-P versus PD and PSP
↓ midbrain/pons ratio in PSP versus PD and MSA-P
Se/Sp for PSP diagnosis: midbrain area = 100%/91.3%; midbrain/pons ratio = 100%/100%

Nicoletti et al., 2006 [48]1.5 TMorphometric measurementsMSA-P = 16; PD = 26; HC = 14
DD (y, M ± SD): MSA-P = 5.06 ± 3.38; PD = 5.92 ± 6.46
↓ MCP width in MSA-P versus PDSe/Sp of MCP width for MSA-P diagnosis = 100%/100%

Quattrone et al., 2008 [37]1.5 TMorphometric measurementsPSP = 33; MSA-P = 19; PD = 108; HC = 50
DD (y, M ± SD): PSP = 3.0 ± 1.6; MSA-P = 4.6 ± 3.1; PD = 5.5 ± 4.3
↓ midbrain area in PSP versus PD and MSA-P
↓ pons area in MSA-P versus PD and PSP
↓ SCP width in PSP versus PD and MSA-P
↓ MCP width in MSA-P versus PD and PSP
↑ pons/midbrain ratio in PSP versus PD and MSA-P
↑ MCP/SCP ratio in PSP versus PD and MSA-P
↑ MRPI in PSP versus PD and MSA-P
Se/Sp for PSP diagnosis: pons/midbrain ratio = 90.9%/93.5% (versus PD), 97%/94.7% (versus MSA-P); MCP/SCP ratio = 78.8%/88.9% (versus PD), 93.9%/89.5% (versus MSA-P); MRPI = 100%/100% (versus PD and MSA-P)

Gama et al., 2010 [49]1.5 TMorphometric measurementsPD = 21; MSA-C = 11; MSA-P = 8; PSP = 20
DD (y, M ± SD): PD = 6.0 ± 3.66; MSA-C = 3.9 ± 1.62; MSA-P = 5.0 ± 3.2; PSP = 5.6 ± 2.28
↓ midbrain area in PSP and MSA-P versus PD, of PSP versus MSA-C and MSA-P and of MSA-P versus MSA-C
↓ pons area PSP, MSA-P, and MSA-C versus PD, of MSA-C and MSA-P versus PSP
↓ MCP diameter in PSP, MSA-C, and MSA-P versus PD, and MSA-C versus PSP
↓ SCP diameter in PSP and MSA-C vs PD, PSP vs MSA-C and MSA-P
Acc/Se/Sp of midbrain area in discriminating PD, PSP, and MSA-C: 80.0%/65.5%/93.5%, 96.7%/95.0%/97.5%, and 51.7%/66.7%/93.8%, respectively
Acc/Se/Sp of pons area in discriminating PD and MSA-C: 90.0%/80.0%/97.1%, 88.3%/77.5%/100%
Acc/Se/Sp of MCP diameter in discriminating PD, PSP, and MSA-C: 85.0%/71.4%/96.9% and 90.0%/66.7%/97.8%
Acc/Se/Sp of SCP diameter in discriminating PD and PSP: 80.0%/65.5%/93.5%

Hussl et al., 2010 [50]1.5 TMorphometric measurementsPSP = 22; MSA-P = 26; PD = 75
DD (y, M ± SD): PSP = 2.88 ± 1.94; MSA-P = 4.09 ± 1.79; PD = 7.49 ± 6.89
↓ midbrain/pons ratio in PSP versus non-PSP
↑ MRPI in PSP versus non-PSP
Se/Sp for PSP diagnosis (versus non-PSP): midbrain/pons ratio = 63.6%/92.1%; MRPI = 81.8%/80.2%

Longoni et al., 2011 [51]1.5 TMorphometric measurementsPSP-RS = 10; PSP-P = 10; PD = 25; HC = 24
DD [y, M, SD (range)]: PSP-RS = 3.8 (2.5–7); PSP-P = 5.1 (3–10); PD = 4.9 (1–19)
↑ pons/midbrain ratio in PSP-RS and PSP-P versus PD
↑ MR parkinsonism index in PSP-RS and PSP versus PD
Se/Sp for PSP diagnosis: pons/midbrain ratio = 90%/96% (PSP-RS versus PD) and 60%/96% (PSP-P versus PD); MRPI = 100%/92% (PSP-RS versus PD) and 70%/68% (PSP-P versus PD)

Morelli et al., 2011 [52]1.5 TMorphometric measurementsProbable PD = 170; possible PD = 132; PSP = 42; HC = 38
DD [y, M, SD (range)]: probable PD = 7.06 ± 3.9 (3–22); possible PD = 3.06 ± 2.4 (1–10); PSP = 3.57 ± 2.4 (1–15)
↓ SCP diameter, MCP diameter, midbrain area, pons area, midbrain/pons ratio, and ↑ MRPI in PSP versus PDAcc/Se/Sp of MRPI in discriminating PSP from possible PD: 99.4%/100%/99.2%
Acc/Se/Sp of MRPI in discriminating PSP from probable PD: 99.5%/100%/99.4%

Nair et al., 2013 [53]3 TMorphometric measurements: volumetry-DTIPD = 26; MSA = 13
DD (m, M ± SD): PD = 8.9 ± 6.5 (range 1–25); MSA = 3.7 ± 2.1 (range 1–7)
↓ mean width and FA of MCP, anteroposterior
diameter and volume of pons, FA and volume of cerebellum, volume of putamen, FA of rostral substantia nigra, and ↑ MD of MCP in MSA versus PD
Overall performance of the decision tree (including mean MCP width and FA and anteroposterior
diameter of pons)
was 92% sensitivity, 96% specificity, 92% PPV, and 96%
NPV

Zanigni et al., 2016 [54]1.5 TMorphometric measurements: volumetry-DTIPSP-RS = 23; PD = 42
DD (y, M ± SD): PSP-RS = 4.2 ± 2.7; PD = 4.0 ± 3.3
↓ MCP and SCP diameters, pons and midbrain areas and ↑ MCP/SCP diameter, pons/midbrain area, and MRPI in PSP-RS versus PD
↑ MD in SCP, thalamus, putamen, pallidus, parietooccipital and prefrontal WM, brain hemispheres, posterior fossa, brainstem, and cerebellar hemispheres in PSP-RS versus PD
↓ FA in SCP, midbrain (SCPs decussation), parietooccipital and prefrontal WM, brain hemispheres, posterior fossa, and brainstem in PSP-RS versus PD
↓ volume of brainstem, nucleus accumbens, globus pallidus, putamina, thalami, and ↑ volume of lateral ventricles in PSP-RS versus PD
Acc/Se/Sp of midbrain area in discriminating PSP-RS from PD: 99%/96%/98%
Acc/Se/Sp of pons/midbrain area in discriminating PSP-RS from PD: 97%/96%/90%
Acc/Se/Sp of MRPI in discriminating PSP-RS from PD: 95%/87%/93%
Acc/Se/Sp of posterior fossa MD in discriminating PSP-RS from PD: 90%/80%/83%
Acc/Se/Sp of SCP MD in discriminating PSP-RS from PD: 88%/70%/98%
Acc/Se/Sp of thalamic volume in discriminating PSP-RS from PD: 83%/73%/90%
Acc/Se/Sp of putaminal volume in discriminating PSP-RS from PD: 83%/93%/70%

Schulz et al., 1999 [55]1.5 TVolumetric measurementsPSP = 6; MSA-P = 12; MSA-C = 17; PD = 11; HC = 16 (age matched)
DD (y, M ± SEM): PSP = 2.3 ± 0.95; MSA-P 3.42 ± 0.67; MSA-C 3.41 ± 0.57; PD = 6.82 ± 0.7
↓ TIV-corrected brainstem volume in PSP, MSA-P, and MSA-C versus HC
↓ TIV-corrected cerebellar volume in MSA-P and MSA-C versus HC
↓ TIV-corrected caudate volume in PSP and MSA-P versus PD and HC
↓ TIV-corrected putaminal volume in PSP and MSA-P versus PD and HC
Not reported

Cordato et al., 2002 [56]1.5 TVolumetric measurementsPSP = 21; PD = 17; HC = 23
DD (m, M ± SD): PSP = 47.7 ± 34.0; PD = 94.3 ± 35.5
↑ ventricular, ↓ whole brain, and frontal GM volumes in PSP versus PD and HCSe/Sp discriminant function including frontal GM volume in differentiating PSP from PD and HC: 95.2% and 90.9%

Gröschel et al., 2004 [57]1.5 TVolumetric measurementsPSP = 33; CBS = 18; HC = 22
DD (y, M ± SD): PSP = 3.6 ± 2.2; CBS 4.6 ± 1.6
↓ brainstem volume (>midbrain) in PSP versus CBS and HC
↓ parietal and occipital lobes volumes (>white matter) in CBS versus PSP and HC
↓ area of CC in CBS versus PSP and HC
Discriminating capacity of a function including midbrain, parietal WM, temporal GM, brainstem, frontal WM, and pons volumes in differentiating PSP from CBS from HC: 84% (95%, 76%, and 83%, resp.)

Paviour et al., 2005 [58]1.5 TVolumetric measurementsPSP = 19; MSA = 10; PD = 12; HC = 12
DD (y, M ± SD): PSP = 4.6 ± 1.6; MSA = 5.4 ± 1.7; PD = 13.25 ± 6.7
↓ TIV-corrected SCP volume in PSP versus MSA, PD, and HC Se/Sp for PSP diagnosis: 74% and 77%

Paviour et al., 2006 [59]1.5 TVolumetric measurementsPSP = 18; MSA = 9; PD = 9; HC = 18
DD (y, M ± SD): PSP = 4.6 ± 1.6; MSA = 5.4 ± 1.7; PD = 12.9 ± 4.3
↓ midbrain and SCP volumes in PSP versus MSA-P, PD, and HC
↓ frontal lobe volume in PSP versus PD and HC
↑ 3rd ventricle volume in PSP versus HC
↓ cerebellar and pontine volumes in MSA-P versus PD and HC
↓ midbrain volume in MSA-P versus HC
Se/Sp for regression analysis including midbrain, SCPs, frontal lobe, 3rd ventricle, and whole brain volumes in discriminating PSP from MSA-P, PD, and NC: 88.9% and 97.3%
Se/Sp of midbrain, SCP, pons, and cerebellar volumes in discriminating PSP from MSA-P: 94.4% and 88.9%

Messina et al., 2011 [60]1.5 TVolumetric measurementsPSP = 32; MSA-P = 15; PD = 72; HC = 46
DD (y, M ± SD): PSP = 3.53 ± 3.5; MSA-P = 3.07 ± 2.2; PD = 6.19 ± 4.5
↓ cerebellar cortex, thalamus, putamen, pallidum, hippocampus, and brainstem and ↑ lateral, 3rd and 4th ventricles volumes in PSP versus PD and HC
↓cerebellar cortex, putamen, pallidum, hippocampus, and brainstem and ↑ 4th ventricle volumes in MSA-P versus PD and HC
↓thalamus volume in PSP versus MSA-P
Not reported

Schocke et al., 2002 [61]1.5 TDWIMSA-P = 10; PD = 11; HC = 7
DD (y, M ± SD): MSA-P = 2.8 ± 0.9; PD = 2.9 ± 1.1
↑ rADC in putamen in MSA-P versus PDSe/Sp for MSA-P diagnosis: 100%/100%

Seppi et al., 2003 [62] 1.5 TDWIPSP = 10; MSA-P = 12; PD = 13
DD (y, M ± SD): PSP = 2.7 ± 1.1; MSA-P = 2.9 ± 1.1; PD = 3.0 ± 1.2
↑ rADC in putamen, caudate, and pallidum in PSP versus PD
↑ rADC in putamen, caudate in MSA-P versus PD
Se/Sp for MSA-P diagnosis (versus PD): putaminal rADC = 100%/100%. Se/Sp for PSP diagnosis (versus PD): putaminal rADC = 90%/100%. No discrimination between MSA-P and PSP

Schocke et al., 2004 [63]1.5 TDWIMSA-P = 11; PD = 17; HC = 10
DD (y, M ± SD): MSA-P = 3.9 ± 1.9; PD = 3.7 ± 1.8
↑ rTrace(D) in putamen, caudate, and pallidum in MSA-P versus PDSe/Sp not reported (but no overlap between MSA-P and PD using putaminal rTrace(D))

Seppi et al., 2004 [64] 1.5 TDWIMSA-P = 15; PD = 17; HC = 10
DD (y, M ± SD): MSA-P = 3.1 ± 1.5; PD = 3.9 ± 0.9
↑ rADC in putamen in MSA-P versus PDSe/Sp for MSA-P diagnosis: 93%/100% (higher compared with [123I]IBZM-SPECT)

Seppi et al., 2006 [65]1.5 TDWIMSA-P = 15; PD = 20; HC = 11
DD (y, M ± SD): MSA-P = 3.5 ± 2.1; PD = 3.9 ± 1.8
↑ rTrace(D) in putamen in MSA-P versus PDSe/Sp not reported [but no overlap between MSA-P and PD using posterior putaminal rTrace(D)]

Nicoletti et al., 2006 [66]1.5 TDWIPSP = 16; MSA-P = 16; PD = 16; HC = 15
DD (y, M ± SD): PSP = 3.3 ± 2.5; MSA-P = 4.9 ± 4.0; PD = 7.5 ± 5.8
↑ rADC in putamen, caudate, pallidum, thalamus, MCP, and pons in MSA-P versus PD
↑ rADC in putamen, caudate, pallidum, and thalamus in PSP versus PD
↑ rADC in putamen, MCP in MSA-P versus PSP
Se/Sp for MSA-P diagnosis: MCP rADC = 100%/100% (versus PD and versus PSP); putaminal rADC = 100%/100% (versus PD), 100%/81.2% (versus PSP); pallidal rADC = 62.5%/93.7% (versus PD); caudate rADC = 75%/93.7% (versus PD). Se/Sp for PSP diagnosis (versus PD): putaminal rADC = 75%/100%

Paviour et al., 2007 [67]1.5 TDWIPSP = 20; MSA-P = 11; PD = 12; HC = 7
DD (y, M ± SD): PSP = 4.5 ± 1.8; MSA = 5.4 ± 1.6; PD = 13.3 ± 6.7
↑ rADC in MCP and rostral pons in MSA-P versus PSP and PD Se/Sp for MSA-P diagnosis (versus PSP and versus PD): MCP rADC = 91%/84%

Köllensperger et al., 2007 [68]n.a.DWIMSA-P = 9; PD = 9; HC = 9
DD (y, M ± SD): MSA = 6.4 ± 2.35; PD = 11.3 ± 6.07
↑ rTrace(D) in putamen in MSA-P versus PDSe/Sp for MSA-P diagnosis: 100%/100% (higher compared with tilt test and heart MIBG scintigraphy)

Nicoletti et al., 2008 [69]1.5 TDWIPSP = 28; MSA-P = 15; PD = 15; HC = 16
DD (y, M ± SD): PSP = 3.2 ± 1.7; MSA = 5.1 ± 4.0; PD = 8.6 ± 3.6
↑ rADC in SCP in PSP versus PD and versus MSA-P Se/Sp for PSP diagnosis: 100%/100% (versus PD), 96.4%/93.3% (versus MSA-P). No basal ganglia analysis

Rizzo et al., 2008 [70] 1.5 TDWIPSP-RS = 10; CBS = 7; PD = 13; HC = 9
DD (y, M ± SD): PSP-RS = 4 ± 3; CBS = 4 ± 3; PD = 14 ± 8
↑ ADC in putamen and SCP in PSP-RS versus PD
↑ ADC in putamen in CBS versus PD
↑ hemispheric median ADC in CBS versus PD and PSP-RS
↓ HSR in CBS versus PD and PSP-RS
Se/Sp for PSP-RS diagnosis (versus PD): putaminal ADC = 80%/77%; SCP ADC = 90%/85%.
Se/Sp for CBS diagnosis: putaminal ADC = 86%/92% (versus PD); hemispheric median ADC = 86%/85% (versus PD), 100%/90% (versus PSP-RS); HSR = 100%/100% (versus PD and PSP-RS)

Pellecchia et al., 2009 [71]1.5 TDWIMSA-P = 9; MSA-C = 12; HC = 11
DD (y, M ± SD): MSA-P = 4.1 ± 1.4; MSA-C = 4.1 ± 2.2
↑ trace (D) values in whole and anterior putamen in MSA-P versus MSA-C and HC
↑ trace (D) values in the cerebellum (WM) and MCP in MSA-C versus MSA-P and HC

Umemura et al., 2013 [72]1.5 TDWI (and 123I-metaiodobenzylguanidine (MIBG) cardiac scintigram)PD = 118; MSA-P = 20
DD (y, M ± SD): PD = 6.8 ± 4.9; MSA-P = 3.6 ± 1.8
↑ putaminal ADC in MSA-P versus PDSe/Sp for MSA-P diagnosis by ADC test: 85.0% and 89.0%

Tsukamoto et al., 2012 [73]3 TDWIPD = 17; PSP = 20; MSA = 25 (5 MSA-P; 20 MSA-C); HC = 18
DD (y, M ± SD): PD = 6.0 ± 3.0; PSP = 4.0 ± 3.0; MSA = 3.4 ± 2.6
↑ rADC in midbrain and globus pallidus in PSP versus PD, MSA, and HC
↑ rADC in the SCP and in the head of the caudate nucleus in PSP versus MSA and HC
↑ rADC in pons, middle cerebellar peduncle, cerebellar white matter, and dentate nucleus in MSA versus PD, PSP, and HC
↑ rADC in the posterior putamen in MSA versus PSP
↑ rADC values in the putamen, globus pallidus, and head of
caudate nucleus in MSA-P versus MSA-C
↑ rADC in the pons, middle cerebellar peduncle, and cerebellar white matter in MSA-C versus MSA-P
Not reported

Blain et al., 2006 [74]1.5 TDTIPSP = 17; MSA = 17 (10 MSA-P and 7 MSA-C); PD = 12; HC = 12
DD (y, M ± SD): PSP = 5.3 ± 2.4; MSA = 5.0 ± 2.3; PD = 6.9 ± 2.0
↑ MD in MCP and pons in MSA versus PSP and PD
↓ FA in MCP in MSA versus PSP and PD
↑ MD in decussation of SCP in PSP versus MSA and PD
↓ FA in decussation of SCP in PSP versus PD
Se/Sp not reported

Ito et al., 2007 [75]3 TDTIMSA = 20 (10 MSA-P and 10 MSA-C); PD = 21; HC = 20
DD (y, M ± SD): MSA = 4 ± 2; PD = 10 ± 8
↑ ADC in putamen, pons, and cerebellum in MSA-P versus PD
↓ FA in putamen, pons, and cerebellum in MSA-P versus PD
Se/Sp for MSA-P diagnosis (versus PD): ADC: putamen = 70%/63.6%, pons = 70%/70%, cerebellum = 60%/87.5%; FA: putamen = 70%/87.5%, pons = 70%/100%, and cerebellum = 70%/63.6%
90% of MSA-P had ↑ ADC and ↓ FA in any of the three areas

Ito et al., 2008 [76]1.5 TDTI/DWIPSP = 7; PD = 29; HC = 19
DD (y, M ± SD): PSP = 3.5 ± 1.6; PD = 4.8 ± 3.3
↑ ADC in CC1 in PSP versus PD and HC and in CC2 in PSP versus PD
↓ FA in CC1 in PSP versus HC and in CC2 in PSP versus PD and HC
Se/Sp of ADC in CC1 and CC2 in differentiating PSP from PD: 100% and 75.9%, and 49.2% and 82.8%, respectively
Se/Sp of FA in CC1 and CC2 in differentiating PSP from PD: 85.7% and 65.5%, and 28.5% and 90.0%, respectively

Chung et al., 2009 [77]1.5 TDWIPD = 12; MSA-P = 10; HC = 10
DD (m, M ± SD): PD = 30.4 ± 22.03; MSA-P = 23.6 ± 12.82
↑ rADC in dorsal putamen and MCP in MSA-P versus PD and HCSe/Sp rADC in dorsal putamen in differentiating MSA-P from PD: 66.67%/80%
Se/Sp rADC in MCP in differentiating MSA-P from PD: 91.67%/100%

Erbetta et al., 2009 [78]1.5 TDTI/DWIPSP = 9; CBS = 11; HC = 7
DD (y, M ± SD): PSP = 3.8 ± 2.2; CBS = 3.0 ± 1.1
↑ ADC in anterior, medial thalamus, and SCP and ↓ FA in anterior cingulum in PSP versus CBS
↑ ADC in precentral and postcentral gyri in CBS versus PSP
Not reported

Focke et al., 2011 [79] 3 TDTIPSP = 9; MSA-P = 10; PD = 12; HC = 13
DD (y, M ± SD): PSP = 2.5 ± 2.3; MSA = 4.5 ± 2.7; PD = 5.8 ± 3.8
↑ MD in pallidum and SN in PSP versus PD and in SN in PSP versus MSA-P Se/Sp not reported. No differences in other basal ganglia and in other groups of patients

Boelmans et al., 2010 [80]1.5 TDTICBS = 14; PD = 14; HC = 14
DD (m, M ± SD): CBS = 40.9 ± 18.9; PD = 34.8 ± 18.7
↑ MD in CC in CBS versus PD and HC
↓ FA in middle-dorsal (sensory) CC in CBS versus PD and HC
Se/Sp MD in the whole CC in differentiating CBS from PD: 79% both
Se/Sp MD in the posterior truncus CC in differentiating CBS from PD: 86% and 71%

Nicoletti et al., 2013 [81]1.5 TDTIPD = 10; MSA-P = 9; MSA-C = 7; PSP-RS = 17; HC = 10
DD (y, M ± SD): PD = 8.3 ± 2.5; MSA-P = 4.4 ± 1.2; MSA-C = 5.4 ± 1.1; PSP-RS = 5.9 ± 1.8
↑ MD infratentorial compartment, brainstem, cerebellar vermis, and hemispheres in MSA-P and MSA-C versus PD and HC
↑ MD infratentorial compartment, brainstem, and cerebellar hemispheres in MSA-P and MSA-C versus PSP-RS
↑ MD infratentorial compartment, brainstem, and cerebellar vermis in PSP-RS versus PD and HC
↑ MD in cerebellar vermis in MSA-C versus MSA-P
Se/Sp of MD of cerebellar hemispheres in discriminating MSA from other groups: 100%/100%

Prodoehl et al., 2013 [82]3 TDTIPD = 15; MSA-P = 14; PSP = 12; ET = 14; HC = 17
DD (y, M ± SD): PD = 10.5 ± 7.3; MSA-P = 7.4 ± 4.0; PSP = 10.5 ± 2.5; ET = 28.2 ± 21.0
FA of SN, AD of putamen, and MD of dentate in discriminating PD from MSA-P and PSP: AUC = 0.99; Se = 90%; and Sp = 100%
FA of SN, RD of SCP, and MCP in discriminating PD from MSA-P: AUC = 0.99; Se = 94%; and Sp = 100%
FA of SN, AD of putamen in discriminating PD from PSP: AUC = 0.96; Se = 87%; and Sp = 100%
FA of caudate, RD of MCP in discriminating MSA-P from PSP: AUC = 0.97; Se = 90%; and Sp = 100%

Baudrexel et al., 2014 [83]3 TDTI/volumetry/FDG-PETPD = 13; PSP = 8; MSA-P = 11; HC = 6
DD (y, M ± SD): PD = 6.4 ± 6.0; PSP = 2.6 ± 1.6; MSA-P = 3.6 ± 2.2
↑ MD in posterior putamen in MSA-P versus PD, PSP, and HC
↑ MD in anterior putamen in MSA-P versus PD
↓ putaminal volume in MSA-P versus PD, PSP, and HC
AUC/Se/Sp of posterior putamen MD in discriminating MSA-P from PD, PSP, and NC: 89%/72.7%/100%
AUC/Se/Sp of putaminal volume in discriminating MSA-P from PD, PSP, and NC: 84%/54.5%/100%

Hess et al., 2014 [84]3 TDTI + volumetricPD = 9; PSP = 5; CBS = 6; HC = 12
DD (y, M ± SD): PD = 8.6 ± 4.2; PSP = 3.8 ± 1.4; CBS = 5.5 ± 1.4
↓ thalamic volume in PSP and CBS versus PD and HC
↑ ADC in thalamus in PSP versus PD and HC
Not reported

Nilsson et al., 2007 [85]3 TDeterministic tractographyPD = 2; MSA = 4; PSP = 3; HC = 2
DD (y, range): PD = 2–10; MSA = 2–6; PSP = 2–6
↓ FA and ↑ ADC in MCP in MSA versus PSP, PD, and HC
↓ FA and ↑ ADC in SCP in PSP versus MSA, PD, and HC
Not reported

Surova et al., 2013 [86]3 TDeterministic tractographyPD = 10; MSA-P = 12; PSP = 16; HC = 16
DD [y, M (range)]: PD = 4.5 (2.0–7.5); MSA-P = 3.0 (2.2–5.0); PSP = 3.5 (2.2–4.0)
↑ MD, RD, and ↓ FA in CC in PSP versus PD and HC
↓ apparent area coefficient in CG and ↑ MD in CST in PSP versus PD
↑ RD in CST in MSA-P versus PD
AUC/Se/Sp of CG apparent area coefficient in differentiating PSP from PD: 0.88/87%/80%
AUC/Se/Sp of CST MD in differentiating PSP from PD: 0.85/94%/80%
AUC/Se/Sp of CC MD in differentiating PSP from PD: 0.85/81%/80%

Rosskopf et al., 2014 [87]3 TDTI/probabilistic tractographyPD = 15; PSP = 15 (7 PSP-RS; 8 PSP-P); HC = 18
DD [y, M (range)]: PD = 4 (1–7); PSP = 3 (2–5)
↓ FA in areas I, II, and III of CC in PSP versus PD and HCNot reported

Surova et al., 2015 [88]3 TDTI/probabilistic tractography//morphometric and volumetric measurementPSP = 27; MSA-P = 11; PD = 10; HC = 21
DD [y, median (IR)]: PSP = 3 (2–4); MSA-P = 3 (3–5); PD = 4 (2–7)
↑ MD in thalamus, ventral anterior, and ventral posterior thalamic nuclei and midbrain in PSP versus MSA-P, PD, and HC
↑ MD in pons and putamen in MSA-P versus PD and HC
↑ MD and ↓ FA of bilateral DRTT in PSP versus MSA-P, PD, and HC
↓ thalamus, putamen, and pallidus volumes and midbrain area in PSP versus MSA-P, PD, and HC in
both cohorts
↓ putamen and pallidus volumes in MSA-P versus PD and HC
Se/Sp of MD of the thalamus, right DRTT, and midbrain in discriminating PSP from PD and MSA-P: 81–77%, 92–81%, and 81-81%, respectively

Meijer et al., 2015 [89]3 TDTIPD = 30; aPS = 19 (12 MSA-P; 3 PSP; 3 DLB)
DD [m, M ± SD]: PD = 21.6 ± 11.9; aPS = 28.4 ± 11.1
↑ MD in putamen, left SCP in MSA-P versus PD
↑ MD in midbrain and right SCP in PSP versus MSA-P, DLB, and PD
Diagnostic accuracy in discriminating aPS from PD = 75%

Eckert et al., 2004 [90]1.5 TMTIPD = 15; PSP = 10; MSA = 12; HC = 20
DD (y, M ± SD): PD = 5.4 ± 4.0; PSP = 4.2 ± 2.7; MSA = 3.6 ± 1.6;
↓ MTR of globus pallidus in PSP versus PD, MSA and HC
↓ MTR of putamen in MSA versus PD and HC
↓ MTR in substantia nigra in PD, PSP, and MSA versus HC
↓ MTR in caudate and prefrontal WM in PSP versus HC

von Lewinski et al., 2007 [91]1 TT2PD = 88; MSA = 52 (47 MSA-P; 5 MSA-C); HC = 29
DD (y, M ± SD): MSA = 4.1 ± 2.0;
↓ T2 signal intensity putamen/caudate and putamen/thalamus in MSA versus PD and HCSe/Sp signal intensity putamen/caudate in discriminating MSA from PD: 65%/95%

Gupta et al., 2010 [92]1.5 TSWI
(semiquantitative hypointensity score)
PD = 11; PSP = 12; MSA-P = 12; HC = 11
DD (y, M ± SD): PD = 8.1 ± 3.9; PSP = 3.5 ± 3.9; MSA-P = 5.4 ± 3.3
↓ signal intensity of red nucleus, substantia nigra in PSP versus MSA-P PD and HC
↓ signal intensity in posterolateral putamen in PSP versus PD
Se/Sp of red nucleus hypointensity score in differentiating PSP from PD and from MSA-P: 66.7%/81.8%–66.7%/83.3%
Se/Sp of putamen hypointensity score in differentiating PSP from PD: 50.0%/90.9%

Boelmans et al., 2012 [93]1.5 TQuantitative T2, T2, and T2′PD = 30; PSP = 12; HC = 24
DD [y, M ± SD (range)]: PD = 9.7 ± 5.2 (0.6–22.7); PSP = 4.5 ± 3.7 (0.7–10.3)
↓ T2′ time in caudate, globus pallidus, and putamen in PSP versus PD and HCClassification of linear discriminant analysis including basal ganglia and thalamus: 74.2%

Wang et al., 2012 [94]1.5 TSWIPD = 16; MSA-P = 8; HC = 44
DD (y, M ± SD): PD = 2.5 ± 1.7; MSA-P = 2.3 ± 1.1
↑ (phase shift values) iron content in putamen and thalamus in MSA-P versus PDAcc of high iron percentage in putamen in discriminating MSA-P from PD: 0.88

Han et al., 2013 [95]3 TSWIPD = 15; PSP = 11; MSA-P = 12; HC = 20
DD (m, M ± SD): PD = 30.3 ± 19.10; PSP = 25.6 ± 11.57; MSA-P = 26.4 ± 6.24
↑ (phase shift values) iron content in the red nucleus, putamen, globus pallidus, and thalamus in PSP versus PD
↑ (phase shift values) iron content in the red nucleus and putamen in MSA-P versus PD
↑ (phase shift values) iron content in substantia nigra in PD versus MSA-P and HC
AUC of putamen in discriminating MSA-P from PSP and PD: 0.836
AUC of globus pallidus and thalamus in discriminating PSP from MSA-P and PD: 0.869 and 0.884, respectively

Lee et al., 2013 [96]3 TR2/volumetryPD = 29; PSP = 13; MSA-P = 15
DD (m, M ± SD): PD = 29.41 ± 22.2; PSP = 27.62 ± 15.5; MSA-P = 22.73 ± 8.7;
↑ R2 in the putamen in MSA-P versus PD and HC
↑ R2 in globus pallidus and caudate in PSP versus PD and HC
↑ R2 in caudate nucleus in PSP versus MSA-P
↓ volume of caudate, putamen, globus pallidus, and thalamus in PSP and MSA-P versus PD and HC
↓ volume of globus pallidus in PSP versus MSA-P
↓ volume of putamen in MSA-P versus PSP
AUC of putaminal volume in discriminating MSA-P from PSP and PD: 0.832
AUC of globus pallidus volume in discriminating PSP from MSA-P and PD: 0.856

Yoon et al., 2015 [97]3 TSWIPD = 30; MSA-P = 17
DD [y, M ± SD (range)]: PD = 6.07 ± 4.93 (1–21); MSA-P = 2.18 ± 1.19 (1–4.5)
↓ signal intensity of bilateral posterior halves, mean
values of the anterior and posterior halves, and the dominant-side posterior half of the putamen in MSA-P versus PD
AUC of signal intensity of the dominant-side posterior half of the putamen in discriminating MSA-P from PD: 0.947

Davie et al., 1995 [98]1.5 T1H-MRS
Single-voxel
PD = 9; MSA-P = 7; MSA-C = 5; HC = 9↓ NAA/Cr and ↓ Cho/Cr in lenticular nucleus in MSA-P versus HC
↓ NAA/Cr in lenticular nucleus in MSA-C versus HC

Federico et al., 1997 [99]1.5 T1H-MRS
Single-voxel
PD = 8; PSP = 5; HC = 9
DD [y, M (range)]: PD = 7 (4–12); PSP = 5 (3–8)
↓ NAA/Cr and ↓ NAA/Cho in lenticular nucleus in PSP versus HCNot reported

Federico et al., 1997 [100]1.5 T1H-MRS
Single-voxel
PD = 12; PSP = 7; MSA = 7; HC = 10
DD [y, M ± SD (range)]: PD = 5.6 ± 2.6 (3–12); MSA = 3.7 ± 1.6 (3–6)
↓ NAA/Cho and ↓ NAA/Cr in lenticular nucleus in PSP and MSA versus HCNot reported

Tedeschi et al., 1997 [101]1.5 T1H-MRS
Single-voxel
PD = 10; PSP = 12; CBS = 9; HC = 11
DD (m, M ± SD): PD = 103 ± 9; PSP = 48 ± 9; CBS = 40 ± 5
↓ NAA/Cr in brainstem, centrum semiovale, and precentral cortices and ↓ NAA/Cho in lenticular nucleus in PSP versus HC
↓ NAA/Cr in centrum semiovale and ↓ NAA/Cho in lenticular nucleus and parietal cortex in CBS versus HC
Not reported

Federico et al., 1999 [102]1.5 T1H-MRS
Single-voxel
PD = 19; PSP = 11; MSA = 14; HC = 12↓ NAA/Cho in lenticular nucleus in PSP and MSA versus PD and HC
↓ NAA/Cr in lenticular nucleus in PD, PSP, and MSA versus HC and in MSA versus PD
Not reported

Abe et al., 2000 [103]1.5 T1H-MRS
Single-voxel
PD = 23; PSP = 12; MSA = 18; CBS = 19; VP = 10; HC = 20
DD (y, M ± SD): PD = 3.6 ± 1.5; PSP = 3.9 ± 1.6; MSA = 4.0 ± 1.5; CBS = 3.6 ± 1.7; VP = 3.4 ± 1.7
↓ NAA/Cr of frontal cortex in PSP, MSA, CBD, and VP versus HC
↓ NAA/Cr of putamen in PSP, MSA, CBD, and PD versus HC
↓ NAA/Cr of frontal cortex and putamen in CBD versus PD, MSA, and VP
↓ NAA/Cr of putamen in PSP versus VP and MSA
Not reported

Clarke and Lowry, 2000 [104]1.5 T1H-MRS
Single-voxel
PD = 6; MSA = 6; HC = 6↓ NAA/Cho and ↑ Cho/Cr in lenticular nucleus in PD versus HCNot reported

Watanabe et al., 2004 [105]3 T1H-MRS
Single-voxel
24 MSA = 24 (13 MSA-C and 11 MSA-P); PD = 11; HC = 18
DD (y, M ± SD): MSA = 3.7 ± 2.4; PD = 4.4 ± 2.2
↓ NAA/Cr of pontine base in all MSA types and of putamen in MSA-P versus HC
↓ NAA/Cr of pontine base and putamen in MSA-P versus PD
Not reported

Vasconcellos et al., 2009 [106]1.5 T1H-MRS
(Single-voxel)
PD = 12; PSP = 11; MSA-P = 7; HC = 10
DD (y, M ± SD): PD = 8.5 ± 3.5; PSP = 6.6 ± 3.1; MSA-P = 8.0 ± 2.0
↓ NAA/Cr of lenticular nucleus in PSP versus PD and HC
↓ NAA/Cr of the hippocampus in PSP versus HC
↓ NAA/Cho of the midbrain in PSP versus MSA-P and HC
Not reported

Guevara et al., 2010 [107]1.5 T1H-MRS
(Multi- and single-voxel)
PD = 11; PSP = 13; MSA-P = 11; MSA-C = 6; HC = 18
DD [y, M ± SD (range)]: PD = 6.9 ± 2.1 (3.9–10.5); PSP = 5.1 ± 2.1 (2.3–10.5); MSA-P = 4.7 ± 2.6 (2.0–9.6); MSA-C = 6.1 ± 2.1 (4.0–9.0)
↓ NAA of putamen and pallidum in MSA-P and PSP versus PD and HC
↓ NAA of pallidum in PSP versus MSA-P
Not reported

Zanigni et al., 2015 [108]1.5 T1H-MRS
(Single-voxel)
PSP-RS = 21; MSA-P = 7; MSA-C = 8; PD = 21; HC = 14
DD [y, median (range)]: PSP-RS = 4 (1–11); MSA-P = 3(0.2–7); MSA-C = 6 (3–13); PD = 3 (1–15)
↓ cerebellar NAA/Cr and NAA/mI ratios in aPS versus PD and HC and in MSA-C versus PSP-RS, MSA-P, and PD ()
↓ cerebellar NAA/Cr ratio in PSP-RS versus PD and NC () and ↓ cerebellar NAA/mI in PSP-RS versus NC ()
Se/Sp of cerebellar NAA/Cr ratio value in discriminating PD from aPS: 100% and 64%.

Acc/Se/Sp: accuracy/sensitivity/specificity; T: Tesla; PSP: Progressive Supranuclear Palsy; PD: Parkinson’s disease; HC: healthy controls; DD: disease duration; y: years; M: mean; SD: standard deviation; MSA: Multiple System Atrophy; MSA-P: parkinsonian variant of MSA; MCP: middle cerebellar peduncle; SCP: superior cerebellar peduncle; MRPI: MR parkinsonism index; MSA-C: cerebellar variant of MSA; PSP-RS: PSP-Richardson’s syndrome; PSP-P: PSP-parkinsonism; m: months; FA: fractional anisotropy; MD: mean diffusivity; TIV: total intracranial volume; SEM: standard error mean; CBS: corticobasal syndrome; CC: corpus callosum; WM: white matter; DWI: diffusion-weighted imaging; rADC: regional ADC; rTrace(D): trace of diffusion tensor; ADC: ADC average; HSR: hemispheric symmetry ratio; ADC: apparent diffusion coefficient; GRE: gradient echo; DTI: diffusion tensor imaging; IR: interquartile range; aPS: atypical parkinsonian syndromes; DLB: dementia with Lewy bodies; MTRI: magnetization transfer imaging; MTR: magnetization transfer; SWI: susceptibility-weighted imaging; AUC: area under the curve; 1H-MRS: proton magnetic resonance spectroscopy; NAA: N-acetyl-aspartate; Cr: creatine; Cho: choline; VP: vascular parkinsonism.