Topography of putaminal degeneration in multiple system atrophy: a diffusion magnetic resonance study.

There is neuropathologic evidence that, in early stages of the Parkinson variant of multiple system atrophy (MSA-P), the putamen shows a distinct topographical pathology affecting predominantly the dorsolateral and caudal regions while leaving the rostral to midparts almost intact. We investigated the topographic profile of putaminal degeneration in MSA-P patients in vivo by means of diffusion-weighted imaging (DWI), which has been shown to reveal abnormalities in the basal ganglia of patients with MSA-P compared to patients with PD and healthy controls. For this purpose, regional trace of the diffusion tensor (rTrace(D)) values were determined in the entire, anterior, and posterior putamen in 15 patients with probable MSA-P, in 20 patients with PD, and in 11 healthy volunteers matched for age and disease duration. MSA-P patients had significantly higher rTrace(D) values in entire, anterior, and posterior putamen compared to both controls and PD patients. Trace(D) values were significantly higher in the posterior compared to the anterior putamen in the MSA-P group. There were no significant differences between posterior and anterior putamen in both the control and PD group. Our study demonstrates prominent involvement of the posterior putamen in early disease stages of MSA-P in vivo by assessing putaminal diffusivity with the help of DWI.     

Comparison of diffusion-weighted imaging and [123I]IBZM-SPECT for the differentiation of patients with the Parkinson variant of multiple system atrophy from those with Parkinson's disease.

Both dopamine D2 receptor (D2R) binding single-photon emission computed tomography (SPECT) with [123I]iodobenzamide (IBZM) and diffusion-weighted imaging (DWI) have been shown to contribute to the differential diagnosis of patients with the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). We aimed to compare these two routinely available functional imaging modalities in differentiating patients with MSA-P from PD. For this purpose, results obtained by DWI and IBZM-SPECT were intraindividually compared in a cross-sectional study of 15 MSA-P and 17 PD patients matched for age and disease duration. The activity ratios of striatal to frontal cortex uptake (S/FC ratio) were used as a semiquantitative measure of the relative density of basal ganglia dopamine receptors labeled by IBZM. Regional apparent diffusion coefficients (rADC) were determined in the striatum. MSA-P patients had significantly lower S/FC ratios and significantly higher striatal rADCs than both PD patients and healthy volunteers. There were no significant differences in S/FC ratios and striatal rADC between PD patients and healthy volunteers. Sensitivity of IBZM-SPECT versus DWI for the differentiation of MSA-P from PD was 80% versus 93%, specificity 71% versus 100%, the predictive accuracy 75% versus 97%, the positive predictive value 71% versus 100%, and the negative predictive value 80% versus 94%. Striatal rADCs had a significant higher overall predictive accuracy than D2R binding with IBZM. In summary, our data suggest that DWI may be more accurate compared to IBZM-SPECT in the differential diagnosis of MSA-P versus PD.     

Evaluating posterolateral linearization of the putaminal margin with magnetic resonance imaging to diagnose the Parkinson variant of multiple system atrophy.

The objective was to develop a simple method for evaluating putaminal atrophy in patients with the Parkinson variant of multiple system atrophy (MSA-P). We used magnetic resonance imaging to study 9 patients with MSA-P, 24 patients with cerebellar variants of multiple system atrophy (MSA-C), 38 patients with Parkinson's disease (PD), and 27 healthy control subjects. Posterolateral linearization of the putaminal margin was semiquantitatively scored and the putaminal area per intracranial area was calculated as the adjusted putaminal area. There was a negative correlation between the linearization scores and adjusted putaminal areas (r = -0.43, P < 0.001), such that the mean adjusted putaminal area in the group without putaminal linearization (0.0148 +/- 0.0022) was greater than that of the group with linearization (0.0124 +/- 0.0029, P < 0.005). Moreover, the occurrence of putaminal linearization was significantly higher in MSA-P patients (88.8%) than in MSA-C (8.3%), PD (7.9%) and healthy subjects (7.4%; P < 0.005). Putaminal linearization was a highly sensitive (0.89) and specific (0.91) measure for differentiating MSA-P. Our results suggest that evaluating posterolateral putaminal linearization is useful for assessing putaminal atrophy and for differentiating MSA-P from MSA-C, PD, and healthy subjects.     

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.     

Diffusion weighted imaging best discriminates PD from MSA-P: A comparison with tilt table testing and heart MIBG scintigraphy.

Both diffusion weighted magnetic resonance imaging (DWI) of the basal ganglia and meta-iodobenzylguanidin (MIBG) scintigraphy of the heart have been reported useful in the differential diagnosis of patients with Parkinson's disease (PD) vs. the parkinson variant of multiple system atrophy (MSA-P). Their diagnostic value, however, has never been directly compared in patients with parkinsonism and autonomic dysfunction. We have studied 9 patients with PD and 9 patients with MSA-P matched for age and disease severity. Regional trace of the diffusion tensor values were determined in the putamina. Cardiac MIBG uptake was quantified by comparing regions of interest over heart and mediastinum Heart/Mediastinum (H/M) ratio. Furthermore, all patients underwent tilt testing. PD patients showed significantly lower H/M ratios than normal controls; however, there was considerable overlap between the two patient groups. We did not detect any significant differences of blood pressure response to passive tilt between the two patient groups. Sensitivity of MIBG scintigraphy versus DWI for the differentiation of MSA-P from PD was 55.6% vs. 100%, specificity 88.8% vs. 100%, and area under the curve 0.802 vs. 1.000. Our data suggest that DWI is superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of PD versus MSA-P.     

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA‐P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA‐P in order to evaluate its differential diagnostic value in vivo. Twenty‐eight patients with PSP (14 with possible‐PSP and 14 with probable‐PSP), 15 PD, 15 MSA‐P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 × 10^?3mm²/s) than patients with PD (median 0.79 × 10^?3 mm²/s, P < 0.001), MSA‐P (median 0.79 × 10^?3 mm²/s, P < 0.001), and healthy controls (median 0.80 × 10^?3 mm²/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA‐P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. © 2008 Movement Disorder Society     

The value of putaminal diffusion imaging versus 18‐fluorodeoxyglucose positron emission tomography for the differential diagnosis of the Parkinson variant of multiple system atrophy

Differentiating the Parkinson variant of multiple system atrophy (MSA‐P) from idiopathic Parkinson's disease (PD) and other forms of atypical parkinsonism can be difficult because symptoms overlap considerably. 18‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is a powerful imaging technique that can assist in the diagnosis of MSA‐P via detection of putaminal and cerebellar hypometabolism. Recent studies suggest that diffusion‐weighted imaging (DWI) might be of similar diagnostic value, as it can detect microstructural damage in the putamen by means of an increased mean diffusivity (MD). The aim of this study was a direct comparison of DWI and FDG‐PET by using both methods on the same subject cohort. To this end, combined DWI and FDG‐PET were employed in patients with MSA‐P (n = 11), PD (n = 13), progressive supranuclear palsy (n = 8), and in 6 control subjects. MD values and FDG uptake ratios were derived from volumetric parcellations of the putamen and subjected to further analysis of covariance (ANCOVA) and receiver operating characteristics analyses. MSA‐P was found to be associated with an increased posterior putaminal MD (P < 0.001 in all subgroup comparisons) that correlated strongly with local reductions in FDG uptake (r = ?0.85, P = 0.002). DWI discriminated patients with MSA‐P from other subgroups nearly as accurately as FDG‐PET (area under the curve = 0.89 vs 0.95, P = 0.27 [pooled data]). Our data suggest a close association between the amount of putaminal microstructural damage and a reduced energy metabolism in patients with MSA‐P. The clinical use of DWI for the differential diagnosis of MSA‐P is encouraged. © 2013 International Parkinson and Movement Disorder Society     

Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.

To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.     

3T MR的T2WI和磁敏感成像序列对帕金森病、进行性核上性麻痹帕金森型及多系统萎缩帕金森型的鉴别价值

目的评估脑部壳核、齿状核、红核、苍白球在磁敏感成像(SWI)的低信号强度与低信号层数,黑质燕尾征的消失及额颞叶萎缩程度对帕金森病(PD)、进行性核上性麻痹帕金森型(PSP-P)及多系统萎缩帕金森型(MSA-P)的鉴别诊断价值。方法采用MRI的T2WI和SWI序列对30名健康对照、80例PD患者、22例PSP-P患者及17例MSA-P患者进行检查,观察患者脑部壳核、齿状核、红核、苍白球在SWI的低信号强度与低信号层数,黑质燕尾征的消失及额颞叶萎缩程度。采用ROC曲线评价其鉴别诊断价值。结果与PD组比较,PSP-P组壳核低信号强度分级显著升高(P=0.007),PSP-P组和MSA-P组红核低信号强度分级显著降低(P=0.000,P=0.000)。与PSP-P组比较,PD组齿状核、苍白球及MSA-P组苍白球低信号层数显著增加(P=0.002,P=0.000,P=0.008)。与正常对照组比较,PD组、PSP-P组和MSA-P组燕尾征消失比率均显著升高(均P<0.008),但PD、PSP-P、MSA-P三组间燕尾征消失比率差异无统计学意义。与PSP-P组比较,PD组和MSA-P组额颞叶萎缩较轻(P=0.000,P=0.001)。壳核低信号强度鉴别PSP-P与PD的最佳截点为0.5,此时敏感度为88.2%,特异性为66.4%,曲线下面积(AUC)为0.70;额颞叶萎缩程度鉴别PD与PSP-P的最佳截点为0.5,在调整为轻度萎缩后,敏感度为88.2%,特异性为45.1%,AUC为0.74。壳核及红核信号强度、齿状核及苍白球层数、额颞叶萎缩程度联合鉴别PSP-P和PD的AUC为0.939,标准误为0.026,P值为0.000。利用燕尾征消失鉴别健康者和PD、PSP-P时,AUC为95.5。结论壳核和红核信号强度分级、齿状核和苍白球层数、额颞叶萎缩程度对PD、PSP-P、MSA-P的鉴别有一定参考价值。     

Differentiating multiple system atrophy from Parkinson's disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging

OBJECTIVES: The differential diagnosis between typical idiopathic Parkinson's disease (PD) and the striatonigral variant of multiple system atrophy (MSA-P) is often difficult because of the presence of signs and symptoms common to both forms of parkinsonism, particularly at symptom onset. This study investigated striatal and midbrain findings in MSA-P and PD patients in comparison with normal controls with the use of positron emission tomography (PET) and three dimensional magnetic resonance imaging (3D MRI) based volumetry to increase the differential diagnostic accuracy between both disease entities. METHODS: Nine patients with MSA-P, 24 patients with PD, and seven healthy controls were studied by MRI and PET with 6-[(18)F]-fluoro-L-dopa (FDOPA), [(18)F]fluoro-deoxyglucose (FDG), and 11-C-Raclopride (RACLO). Striatal and extrastriatal volumes of interest (VOI) were calculated on the basis of the individual MRI data. The PET data were transferred to the VOI datasets and subsequently analysed. RESULTS: MSA-P differed significantly from PD patients in terms of decreased putaminal volume, glucose metabolism, and postsynaptic D2 receptor density. The striatal FDOPA uptake was equally impaired in both conditions. Neither MRI volumetry nor PET imaging of the midbrain region further contributed to the differential diagnosis between PD and MSA-P. CONCLUSIONS: The extent and spatial distribution of functional and morphological changes in the striatum permit the differentiation of MSA-P from PD. Both, multi-tracer PET and 3D MRI based volumetry, may be considered equivalent in the assessment of different striatal abnormality in both disease entities. In contrast, MRI and PET imaging of the midbrain does not provide a further gain in diagnostic accuracy.     

Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker

OBJECTIVE: We performed (1)H-MR spectroscopy ((1)H-MRS) on multiple brain regions to determine the metabolite pattern and diagnostic utility of (1)H-MRS in multiple system atrophy (MSA). METHODS: Examining single voxels at 3.0 T, we studied metabolic findings of the putamen, pontine base, and cerebral white matter in 24 MSA patients (predominant cerebellar ataxia (MSA-C), n = 13), parkinsonism (MSA-P), n = 11), in 11 age and duration matched Parkinson's disease patients (PD) and in 18 age matched control subjects. RESULTS: The N-acetylaspartate to creatine ratio (NAA/Cr) in MSA patients showed a significant reduction in the pontine base (p<0.0001) and putamen (p = 0.02) compared with controls. NAA/Cr in cerebral white matter also tended to decline in long standing cases. NAA/Cr reduction in the pontine base was prominent in both MSA-P (p<0.0001) and MSA-C (p<0.0001), and putaminal NAA/Cr reduction was significant in MSA-P (p = 0.009). It was also significant in patients who were in an early phase of their disease, and in those who showed no ataxic symptoms or parkinsonism, or did not show any MRI abnormality of the "hot cross bun" sign or hyperintense putaminal rims. NAA/Cr in MSA-P patients was significantly reduced in the pontine base (p = 0.001) and putamen (p = 0.002) compared with PD patients. The combined (1)H-MRS in the putamen and pontine base served to distinguish patients with MSA-P from PD more clearly. CONCLUSIONS:(1)H-MRS showed widespread neuronal and axonal involvement in MSA. The NAA/Cr reduction in the pontine base proved highly informative in the early diagnosis of MSA prior to MRI changes and even before any clinical manifestation of symptoms.     

Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico-radiological correlations.

Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders, each with a prevalence of around 5 per 100,000. Regional brain atrophy patterns differ in the two disorders, however, and magnetic resonance imaging is sometimes helpful in distinguishing them in the later stages. We measured whole brain and regional volumes, including cerebellum, pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as well as frontal and posterior-inferior cerebral regions in 18 subjects with PSP, 9 with MSA-P (parkinsonian phenotype), 9 with Parkinson's disease (PD), and 18 healthy controls. Associations between these volumes, cognitive profiles, and clinical measures of disease severity and motor disability were assessed. Mean midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15% smaller than in MSA-P (P = 0.009). The mean SCP volume in PSP was 30% smaller than in MSA-P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA-P were 20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean pontine volume in MSA-P was 30% smaller than in PD or controls (P < 0.001) and 25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated with midbrain volume, and more severe executive dysfunction was associated with reduced frontal volume. These distinct patterns of cortical and subcortical atrophy, when considered together rather than independently, better differentiate PSP and MSA-P from each other and also from healthy controls.     

Brain magnetic resonance imaging in multiple-system atrophy and Parkinson disease: a diagnostic algorithm

BACKGROUND: Brain magnetic resonance (MR) imaging offers the potential for objective criteria in the differential diagnosis of multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson disease (PD), since it frequently shows characteristic abnormalities in patients with MSA-P and is believed to be normal in patients with PD. OBJECTIVE: To determine concordance between clinical and MR imaging-based diagnoses of MSA-P and PD. DESIGN: Two neuroradiologists identified and rated striatal and infratentorial abnormalities in 39 brain MR images and assigned a diagnosis of PD, MSA-P, or MSA with additional marked cerebellar ataxia (MSA-C). SETTING: Academic medical center. PATIENTS: Thirty-nine patients with parkinsonism, including 21 with a clinical diagnosis of PD, 14 with MSA-P, and 4 with MSA-C. RESULTS: All patients with MSA and 14 (67%) of 21 patients with PD had some abnormality on brain MR imaging. Brainstem atrophy was seen in patients with MSA-P and MSA-C. Putaminal atrophy was seen only in MSA-P. Putaminal hypointensity and lateral slitlike hyperintensity were seen in both PD and MSA-P but were always mild in PD. Cerebellar abnormalities, seen in all patients with MSA-C and 11 patients with MSA-P, were also identified in 6 patients with PD, albeit always rated as mild. Nonconcordance between clinical and radiological diagnosis occurred in 2 patients with PD, 5 with MSA-P, and 1 with MSA-C. CONCLUSION: Since several features on brain MR imaging are seen only in MSA-P, a simple diagnostic algorithm may improve the MR imaging diagnosis of MSA-P and PD.     

Diffusion-weighted imaging and its relationship to microglial activation in parkinsonian syndromes

Microglial activation has been implicated in the pathogenesis of Parkinson's disease (PD) and atypical parkinsonian syndromes, and regional microstructural changes have been identified using diffusion-weighted MR imaging. It is not known how these two phenomena might be connected.We hypothesized that changes in regional apparent diffusion coefficient (rADC) in atypical parkinsonian syndromes would correlate with microglial activation.In our study we have evaluated changes in rADC in 11 healthy controls, 9 patients with PD and 11 with either multiple system atrophy or progressive supranuclear palsy. The patients also underwent [¹¹C]-(R)-PK11195 positron emission tomography, a marker of microglial activation.Increased rADC was found compared to controls in the thalamus and midbrain of all parkinsonian patients, and in the putamen, frontal and deep white matter of patients with atypical parkinsonian syndromes. Putaminal rADC alone did not reliably differentiate PD from atypical parkinsonism. There was no correlation between [¹¹C]-(R)-PK11195 binding potential and rADC in the basal ganglia in atypical parkinsonian syndromes. However, pontine PK11195 binding and rADC were positively correlated in atypical parkinsonism (r = 0.794, p = 0.0007), but not PD patients.In conclusion, microglial activation does not appear to contribute to the changes in putaminal water diffusivity associated with atypical parkinsonian syndromes, but may correlate with tissue damage in brainstem regions.     

Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies

There is evidence that the α-synucleinopathies Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Despite the considerable clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal and rapidly progressive. Moreover recent clinical studies have shown that surrogate markers of disease progression can be quantified easily and may reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be exploited as a filter barrier in the development of disease-modifying therapeutic strategies targeting common pathophysiological mechanisms of α-synucleinopathies. This approach might reduce the number of negative phase III clinical trials, and, in turn, shift the available resources to earlier development stages, thereby increasing the number of candidate compounds validated.     

Individual voxel-based morphometry adjusting covariates in multiple system atrophy

IntroductionThis study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD).MethodsWe included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI.ResultsOn iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD.ConclusioniVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.     

Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise [123I]beta-CIT SPECT analysis

BACKGROUND: Dopaminergic loss can be visualized by means of iodine I 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon emission computed tomography (SPECT) in several neurodegenerative parkinsonian disorders. Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent. OBJECTIVE: To objectively localize the cerebral dopamine transporter status in the early stages of progressive supranuclear palsy (PSP). DESIGN: Prospective study. SETTING: Parkinson disease outpatient clinic. PATIENTS: Fourteen patients with PSP, 17 with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy (MSA-P), and 13 healthy control subjects, matched for age and disease duration. INTERVENTIONS: Statistical parametric mapping applied to [(123)I]beta-CIT SPECT. MAIN OUTCOME MEASURES: Differences in [(123)I]beta-CIT uptake. RESULTS: All patients with the different parkinsonian disorders showed a significant decrease in striatal [(123)I]beta-CIT uptake without any overlap with the control group. In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta-CIT signal compared with controls and patients with PD was identified with statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated atypical parkinsonian disorders from PD with an overall correct classification of 91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and MSA-P. CONCLUSION: By applying statistical parametric mapping to [(123)I]beta-CIT SPECT images of patients with PSP, a widespread decline of monoaminergic transporter availability including the striatum and brainstem was localized in PSP, discriminating patients with PSP from patients with PD, but not from those with MSA-P. Quantification of midbrain dopamine transporter signal may therefore enhance the utility of SPECT imaging in the differential diagnosis of patients with parkinsonism.     

A magnetization transfer study of mild and advanced Parkinson’s disease

Background and purpose: Magnetization transfer ratio (MTR) technique has identified brain changes in grey and white matter in Parkinson’s disease (PD), even in the early phase. However, how these tissue changes differ along the course of the illness is still unclear. This study was aimed at investigating how MTR values change from mild PD (PD1) to patients with advanced PD (PD2). Methods: We measured MTR values by region of interest, in 11 PD1, 11 PD2 and 10 healthy age‐matched subjects. Results: Compared with controls, patients with PD1 exhibited a significant MTR reduction in substantia nigra pars compacta, substantia nigra pars reticulata, putamen, periventricular white matter and parietal white matter. In addition to the changes observed in PD1, the PD2 group exhibited a significant MTR reduction in caudate, pons, frontal white matter and lateral thalamus. Conclusion: These results suggest that MTR might reflect morphological changes induced by the disease in distinct brain areas at different stages.     

Diffusion‐weighted imaging in multiple system atrophy: A comparison between clinical subtypes

Multiple system atrophy can be classified into two main types, a Parkinsonian (MSA‐P) and a cerebellar (MSA‐C) variant based on clinical presentation. We obtained diffusion‐weighted magnetic resonance imaging (DWI) in 9 MSA‐P and 12 MSA‐C patients and 11 controls, and correlated DWI changes with disease duration and severity. We found that Trace (D) values in the entire and anterior putamen were significantly higher in MSA‐P than in MSA‐C patients and controls, whereas Trace (D) values in the cerebellum and middle cerebellar peduncle (MCP) were significantly higher in MSA‐C than in MSA‐P patients and controls. Increased disease duration was significantly correlated with increased Trace (D) values in pons of MSA‐P patients, and in cerebellum and MCP of MSA‐C patients. Both UMSARS and UPDRS motor scores positively correlated with entire and posterior putaminal Trace (D) values in MSA‐P patients. The diffusivity changes parallel phenotypical and pathologic differences between MSA‐P and MSA‐C patients, suggesting that DWI is a feasible tool for in vivo evaluation of neurodegeneration in MSA. Based on our findings, Trace (D) measurements in the putamen and pons in MSA‐P patients and in the cerebellum and MCP in MSA‐C patients could serve as quantitative markers for microstructural damage in the course of disease. © 2008 Movement Disorder Society     

Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT.

Sixteen patients with a clinical diagnosis of probable multiple system atrophy (MSA) were examined clinically by MRI and by 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT). The clinical records of another 16 patients were also analysed retrospectively. On the basis of their clinical presentation, patients were subdivided into those with prominent parkinsonism (MSA-P, n = 11) and those with prominent cerebellar ataxia (MSA-C, n = 21). Autonomic symptoms were present in all patients and preceded the onset of motor symptoms in 63% of patients. Calculated median lifetime and the median time to become wheelchair bound after onset of disease were significantly shorter for MSA-P than for MSA-C (lifetime: 4.0 v 9.1 years; wheelchair: 3.1 vs 5.0 years) suggesting a better prognosis for cerebellar patients. A significant loss of striatal dopamine receptors (below 2 SD threshold) was detected by IBZM-SPECT in 63% of the patients (56% below 2.5 SD threshold). There was no difference between patients with MSA-C and those with MSA-P in the proportion with significant receptor loss and the extent of dopamine receptor loss. Planimetric MRI evaluation showed cerebellar and brainstem atrophy in both groups. Atrophy was more pronounced in patients with MSA-C than in those with MSA-P. Pontocerebellar hyperintensities and putaminal hypointensities on T2 weighted MRI were found in both groups. Pontocerebellar signal abnormalities were more pronounced in MSA-C than in MSA-P, whereas the rating scores for area but not for intensity of putaminal abnormalities were higher in MSA-P. MRI and IBZM-SPECT provide in vivo evidence for combined basal ganglia and pontocerebellar involvement in almost all patients in this series.