Multiple System Atrophy Group Research Articles

131I-MIBG myocardial scintigraphy for differentiation of Parkinson's disease from multiple system atrophy or essential tremor in Chinese population

ObjectiveClinical distinction of Parkinson's disease (PD) from multiple system atrophy (MSA) or essential tremor (ET) is sometimes difficult. The purpose of this study was to assess changes in cardiac sympathetic nerve function in PD, MSA, and ET by 131I-MIBG myocardial scintigraphy MethodsPatients with PD (25), MSA (18), or ET (11) and 10 healthy controls (HC) were enrolled. 131I-MIBG myocardial scintigraphy was performed for each subject, and heart/mediastinum (H/M) ratios were calculated at two sample times (15min and 4h after the injection of 131I-MIBG), representing the 131I-MIBG myocardial uptake ratios. The washout ratio (WOR) of MIBG which indicates the activity tone of the presynaptic sympathetic nerves was calculated for each subject. ResultsThe H/M ratios at the two sample times (15min and 4h) were 1.65±0.36 and 1.50±0.43 in the PD group, 1.97±0.36 and 2.08±0.57 in the MSA group, 2.34±0.34 and 2.46±0.51 in the ET group, and 2.41±0.26 and 2.66±0.47 in the HC group. The H/M ratios at the two sample times were lower in the PD group than in the MSA, ET, or HC groups, with statistical significance (all P<0.05). The H/M ratios at the two sample times were significantly lower in the MSA group than in the HC group (all P<0.05). There was no significant difference in H/M ratios at either sample time between the ET and HC group (all P>0.05). The washout ratios (WORs) of MIBG were significantly increased in PD group compared with those in MSA, ET and HC groups. In subgroup analysis, The H/M ratios at the two sample times were decreased in early PD group compared with those in early MSA and early ET groups, with statistical significance (all P<0.05). ConclusionsCardiac sympathetic dysfunction can occur in both PD and MSA patients, especially in PD patients, whereas it remains normal in ET patients. 131I-MIBG myocardial scintigraphy can help distinguish patients with PD from those with MSA or ET with good sensitivity and specificity.

Characteristics of sympathetic skin response in patients with multiple system atrophy

Objective: To provide evidence for early clinical diagnosis of multiple system atrophy(MSA)by studying the characteristics of sympathetic skin responses(SSR) in the patients with MSA. Methods: A total of 47 MSA patients and 32 healthy individuals were enrolled as case group and normal control(NC) group, from in and out patients of Neurology Department of Navy General Hospital from July 2013 to August 2015. SSR was tested by Nicolet electromyography, the latency and abnormal and disappeared rate of SSR were compared. Results: The SSR latency of upper limbs and lower limbs in MSA group had statistical significance compared respectively with the NCgroup (upper limbs: SSR latency was(1 485±187)ms in MSA group, and(1 375±108)ms in NC group, P<0.05; lower limbs: SSR latency was(2 200±386)ms in MSA group, and(1 994±240)ms in NC group, P<0.05). Sex and age had no significant effect on the latency and the abnormal and disappeared rate of SSR in two groups (P>0.05). The upper and lower limb SSR latency in MSA patients with disease duration more than 2 years(SSR latency was (1 592±160)ms in upper limb and (2 268±254)ms in lower limb) were longer than those within 2 years(SSR latency was (1 453±184)ms in upper limb and (2 190±442)ms in lower limb), but only the upper limbs had significantly statistical differences (P<0.05). Both SSR abnormal rate and SSR disappeared rate in MSA patients whose disease duration were more than 2 years(SSR abnormal rate: 85.00%, SSR disappeared rate: 75.00%) were higher than those with shorter disease duration(SSR abnormal rate: 55.56%, SSR disappeared rate: 22.22%), and both were statistically significant (SSR abnormal rate: P<0.05, SSR disappeared rate: P<0.001). The upper and lower limb SSR latency of MSA-C subgroup had no statistical difference compared with MSA-P subgroup(P>0.05). The SSR abnormal rate in MSA-C subgroup(78.13%) was higher than that of MSA-P subgroup(46.76%), and were statistically significant (P<0.05). The SSR disappeared rate in MSA-C subgroup has no statistical difference compared with the MSA-P subgroup(P>0.05). Conclusions: SSR is helpful to diagnose MSA. The latency and the abnormal and disappeared rate of SSR are significantly increased with the extension of MSA duration. The SSR abnormal rate in MSA-C patients is higher than that in MSA-P patients, and symmetrically abnormal SSR is more supporting the diagnosis of MSA.

Altered bulbocavernosus reflex in patients with multiple system atrophy

Objectives: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR.Methods: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses.Results: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively).Discussion: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients.

Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease.

Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as “gold standard”. The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP ≥ 14 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP ≥ 18 mmHg or DBP ≥ 8 mmHg for severe OH. In PD group, drops in sitting SBP ≥ 10 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons.

Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy.

The COQ2 gene encodes an essential enzyme for biogenesis, coenzyme Q10 (CoQ10). Recessive mutations in this gene have recently been identified in families with multiple system atrophy (MSA). Moreover, specific heterozygous variants in the COQ2 gene have also been reported to confer susceptibility to sporadic MSA in Japanese cohorts. These findings have suggested the potential usefulness of CoQ10 as a blood-based biomarker for diagnosing MSA. This study measured serum levels of CoQ10 in 18 patients with MSA, 20 patients with Parkinson’s disease and 18 control participants. Although differences in total CoQ10 (i.e., total levels of serum CoQ10 and its reduced form) among the three groups were not significant, total CoQ10 level corrected by serum cholesterol was significantly lower in the MSA group than in the Control group. Our findings suggest that serum CoQ10 can be used as a biomarker in the diagnosis of MSA and to provide supportive evidence for the hypothesis that decreased levels of CoQ10 in brain tissue lead to an increased risk of MSA.

Differentiation of Parkinsonism-Predominant Multiple System Atrophy from Idiopathic Parkinson Disease Using 3T Susceptibility-Weighted MR Imaging, Focusing on Putaminal Change and Lesion Asymmetry.

Asymmetric presentation of clinical feature in parkinsonism is common, but correlatable radiologic feature is not clearly defined. Our aim was to evaluate 3T susceptibility-weighted imaging findings for differentiating parkinsonism-predominant multiple system atrophy from idiopathic Parkinson disease, focusing on putaminal changes and lesion asymmetry. This retrospective cohort study included 27 patients with parkinsonism-predominant multiple system atrophy and 50 patients with idiopathic Parkinson disease diagnosed clinically. Twenty-seven age-matched subjects without evidence of movement disorders who underwent SWI were included as the control group. A consensus was reached by 2 radiologists who visually assessed SWI for the presence of putaminal atrophy and marked signal hypointensity on each side of the posterolateral putamen. We also quantitatively measured putaminal width and phase-shift values. The mean disease duration was 4.7 years for the patients with parkinsonism-predominant multiple system atrophy and 7.8 years for the patients with idiopathic Parkinson disease. In the patients with parkinsonism-predominant multiple system atrophy, putaminal atrophy was frequently observed (14/27, 51.9%) and was most commonly found in the unilateral putamen (13/14). Marked signal hypointensity was observed in 12 patients with parkinsonism-predominant multiple system atrophy (44.4%). No patients with idiopathic Parkinson disease or healthy controls showed putaminal atrophy or marked signal hypointensity. Quantitatively measured putaminal width, phase-shift values, and the ratio of mean phase-shift values for the dominant and nondominant sides were significantly different between the parkinsonism-predominant multiple system atrophy group and the idiopathic Parkinson disease and healthy control groups (P < .001). 3T SWI can visualize putaminal atrophy and marked signal hypointensity in patients with parkinsonism-predominant multiple system atrophy with high specificity. Furthermore, it clearly demonstrates the dominant side of putaminal changes, which correlate with the contralateral symptomatic side of patients.

Automatic Evaluation of Speech Rhythm Instability and Acceleration in Dysarthrias Associated with Basal Ganglia Dysfunction.

Speech rhythm abnormalities are commonly present in patients with different neurodegenerative disorders. These alterations are hypothesized to be a consequence of disruption to the basal ganglia circuitry involving dysfunction of motor planning, programing, and execution, which can be detected by a syllable repetition paradigm. Therefore, the aim of the present study was to design a robust signal processing technique that allows the automatic detection of spectrally distinctive nuclei of syllable vocalizations and to determine speech features that represent rhythm instability (RI) and rhythm acceleration (RA). A further aim was to elucidate specific patterns of dysrhythmia across various neurodegenerative disorders that share disruption of basal ganglia function. Speech samples based on repetition of the syllable /pa/ at a self-determined steady pace were acquired from 109 subjects, including 22 with Parkinson’s disease (PD), 11 progressive supranuclear palsy (PSP), 9 multiple system atrophy (MSA), 24 ephedrone-induced parkinsonism (EP), 20 Huntington’s disease (HD), and 23 healthy controls. Subsequently, an algorithm for the automatic detection of syllables as well as features representing RI and RA were designed. The proposed detection algorithm was able to correctly identify syllables and remove erroneous detections due to excessive inspiration and non-speech sounds with a very high accuracy of 99.6%. Instability of vocal pace performance was observed in PSP, MSA, EP, and HD groups. Significantly increased pace acceleration was observed only in the PD group. Although not significant, a tendency for pace acceleration was observed also in the PSP and MSA groups. Our findings underline the crucial role of the basal ganglia in the execution and maintenance of automatic speech motor sequences. We envisage the current approach to become the first step toward the development of acoustic technologies allowing automated assessment of rhythm in dysarthrias.

Esophageal Involvement in Multiple System Atrophy.

The prevalence of esophageal involvement and its impact on clinical manifestations in patients with multiple system atrophy (MSA) remains unknown. We recruited 16 consecutive patients with dysphagia associated with MSA (MSA group) and 16 consecutive patients with dysphagia associated with amyotrophic lateral sclerosis (ALS group). We assessed the presence or absence of food stagnation within the esophagus using videofluorography. Food stagnation within the esophagus was observed in 16 patients (100%; 7 severe, 9 mild) in the MSA group and in 4 patients (25%; 4 mild) in the ALS group (P<0.001). Follow-up videofluorography revealed that food stagnation in patients with MSA could exacerbate during the disease course. Patients with MSA and severe food stagnation showed a wide range of intraesophageal stasis by videofluorography. Among the 16 patients in the MSA group, 4 developed aspiration pneumonia and 1 died of suffocation associated with food regurgitation during continuous positive airway pressure therapy. In conclusion, food stagnation within the esophagus occurs more frequently in MSA patients with dysphagia than in ALS patients with dysphagia. Because food stagnation can cause serious complications such as aspiration pneumonia and suffocation, patients with MSA should be evaluated by videofluorography, especially those with stagnation in the esophageal phase.

Cognitive Impairment and Its Structural Correlates in the Parkinsonian Subtype of Multiple System Atrophy

Background/Aims: Previous studies indicate that patients with the parkinsonian subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This study aimed to identify the existence of cognitive impairments and the different topographic patterns of morphological changes in MSA-P by means of imaging analysis, and also whether these morphological changes could be associated with cognitive dysfunctions in MSA-P. Methods: We recruited 15 nondemented probable MSA-P patients and 32 normal controls (NC) for neuropsychological testing and MRI. We analyzed morphological changes using cortical thickness analysis, voxel-based morphometry (VBM) and cerebellar volumetry. Multiple linear regression analysis was performed to evaluate the correlation of each cognitive score with the mean thickness of significant cortical-thinning clusters, mean gray-matter density of VBM clusters and cerebellar volume. Results: The scores on the Digit Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic Controlled Oral Word Association Test and the Stroop color test were significantly lower in the MSA-P group than in the NC group. We found two clusters exhibiting significant cortical thinning in the right paracentral lobule and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and frontal cortical areas. Multiple linear regression analysis demonstrated that cognitive dysfunction correlated significantly with thinning in the neocortex, cerebellum and striatum. Conclusions: Our data demonstrate that cortical and cerebellar atrophy and striatal degeneration are associated with cognitive impairment in patients with MSA-P.

Differentiation among parkinsonisms using quantitative diffusion kurtosis imaging.

Differential diagnoses among Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy syndrome (PSPS) are often difficult. Hence, we investigated whether diffusion kurtosis imaging (DKI) could detect pathological changes that occur in these disorders and be used to differentiate between such patients. Fourteen patients (five with PD, four MSA, and five PSPS) and six healthy controls were examined using a 1.5-T scanner. Mean kurtosis (MK), fractional anisotropy, and mean diffusivity maps were generated, and these values of the midbrain tegmentum (MBT) and pontine crossing tract (PCT), as well as MBT/PCT ratios, were obtained. We found no significant differences in MBT and PCT values on DKI maps among the groups. In contrast, MBT/PCT ratios from MK maps were significantly increased in the MSA group and decreased in the PSPS group compared with the other groups. MBT/PCT ratios from mean diffusivity maps showed a significant increase in the PSPS group. Therefore, quantitative DKI analyses, particularly the MBT/PCT ratio from MK maps, can differentiate patients with parkinsonisms.

Decreased vesicular storage and aldehyde dehydrogenase activity in multiple system atrophy.

Parkinson disease (PD) and multiple system atrophy (MSA) share some neuropathologic features (nigrostriatal dopaminergic lesion, alpha-synuclein deposition) but not others (Lewy bodies in PD, glial cytoplasmic inclusions in MSA). In PD evidence has accrued for a vesicular storage defect and decreased aldehyde dehydrogenase (ALDH) activity in residual dopaminergic terminals, resulting in accumulation of the toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). In this study we asked whether MSA entails a similar abnormal neurochemical pattern. DA and its main neuronal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its main neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG), the catecholamine precursor DOPA, and DOPAL were measured in striatal and frontal cortical tissue from patients with pathologically proven end-stage MSA (N=15), sporadic PD (N=17), and control subjects (N=18). Compared to the control group, the MSA and PD groups had similarly decreased putamen DA (by 96% and 93%, p<0.0001), DOPAC (97% and 95%, p<0.0001), NE (91% and 74%, p<0.0001), and DHPG (81% and 74%, p<0.0001). In the MSA and PD groups, ratios of DOPAL:DA were 2.3 and 3.5 times control and DHPG:NE 3.1 and 2.6 times control, while DOPAC:DOPAL ratios were decreased by 61% and 74%. In both diseases cortical NE and DHPG were decreased, while DA and DOPAC were not. MSA and PD entail a catecholamine metabolic profile indicating impaired vesicular storage, decreased ALDH activity, and DOPAL buildup, which might be part of a common pathway in catecholamine neuronal death. Targeting this pathway by interfering with catecholaldehyde production or effects constitutes a novel treatment approach.

SNP rs11931074 of the SNCA gene may not be associated with multiple system atrophy in Chinese population

Background: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by poorly levodopa-responsive parkinsonism, cerebellar ataxia, and autonomic dysfunction. Pathogenic mechanisms remain obscure, but the neuropathological hallmark is the presence of α-synuclein-positive glial cytoplasmic inclusions. Previous studies suggested that a single nucleotide polymorphism (SNP), rs11931074, in the α-synuclein gene, SNCA, had highly significant association with an increased risk of the development of MSA in the Caucasian subjects. In contrast, a Korean study failed to identify an association with disease risk. Methods: To study the effect of rs11931074 on MSA risk in a Chinese population, we conducted a case–control study and genotyped SNP rs11931074 by Sanger sequencing in 96 Chinese patients with MSA and 120 healthy controls. Moreover, we performed a meta-analysis on the topic. Results: There was no statistical difference in genotypes or allele frequencies of SNP rs11931074 between MSA and control groups in our cohort. The results of meta-analysis showed that the risk allele T of rs11931074 was associated with MSA (pooled odds ratio = 1.26, 95% confidence interval = 1.07–1.49, P = 0.006). Conclusions: Despite a positive result of the meta-analysis, the significant difference in frequency of allele T of rs11931074 between Asian and Caucasian subjects indicates that population heterogeneity at rs11931074 may exist.

Neuropathological features of multiple system atrophy with cognitive impairment.

Cognitive impairment (CI) is an exclusion criterion for the diagnosis of multiple system atrophy (MSA), according to the second consensus statement. This view was recently challenged by patients with pathologically confirmed MSA who were reported to have dementia. With an aim to investigate the pathological substrate of CI in MSA, quantitative assessment of the glial and neuronal cytoplasmic inclusions and semiquantitative assessment of neuronal loss in the cortical and limbic regions was performed. No differences in the severity of these MSA-related pathological findings were identified between nine MSA cases with CI and nine MSA cases with normal cognition. Alzheimer's-related pathological changes, cerebral amyloid angiopathy, and cerebrovascular disease did not differ between the two MSA groups. MSA-specific α-synuclein and secondary pathological conditions were not more severe in MSA cases with CI, suggesting that although CI may be intrinsic to the MSA disease process, further investigation into the pathological basis of cognitive impairment in MSA is warranted.

Topographic distribution of cortical thinning in subtypes of multiple system atrophy

Background and purposeDespite the predominant degeneration of subcortical structures, recent studies have suggested the evidence of cortical involvement in multiple system atrophy (MSA). This study aimed to identify the different topographic pattern of cortical thinning in MSA according to clinical subtypes, and the association of cortical thinning with cerebellar atrophy and other disease related metrics. Materials and methodsWe used cortical thickness analysis in 53 non-demented probable MSA patients (29 with MSA-C, 24 with MSA-P) and 35 healthy subjects and modeled local cortical thickness as a linear association with cerebellar volume and disease related metrics including age, disease duration, cognition and disease severity. ResultsWe found five clusters (left ventromedial prefrontal, bilateral ventrolateral prefrontal cortex, right parahippocampal and lingual gyrus) exhibiting significant cortical thinning in MSA-C and two clusters (right primary sensory motor and left ventromedial prefrontal cortex) exhibiting a thinning tendency in MSA-P compared with the control group. In correlation analysis, we identified no cluster exhibiting a significant correlation with cerebellar atrophy in both of the MSA groups. However, cortical thickness in right parahippocampalgyrus and left ventrolateral prefrontal cortex showed significant negative correlation with International Cooperative Ataxia Rating Scale subscore of speech disorder in MSA-C group. ConclusionsWe identified different topographic distributions of cortical thinning in MSA subtypes. Our study suggests that cortical thinning of MSA occurs independently of cerebellar atrophy as a primary disease process rather than secondary deafferentation.

Quantitative assessment of subcortical atrophy and iron content in progressive supranuclear palsy and parkinsonian variant of multiple system atrophy

It is a matter of debate whether increased brain iron levels are the cause or only the consequence of neurodegenerative process in degenerative parkinsonism. The aim of this study is to characterize disease-related changes in volumes and iron-related R2 values of basal ganglia and thalamus. 13 patients with progressive supranuclear palsy (PSP), 15 with a parkinsonian variant of multiple system atrophy (MSA-p), 29 with Parkinson's disease (PD), and 21 age-matched controls underwent 3-Tesla MRI. The R2 values and volumes were calculated for the selected subcortical structures (caudate nucleus, putamen, globus pallidus, and thalamus) using an automated region-based analysis. Voxel-based analysis was also performed to visualize a topographical correlation of R2 value and volume. The PSP group had significantly higher R2 values in globus pallidus and caudate nucleus (p < 0.05), whereas the MSA-p group had higher R2 values in putamen (p < 0.001) than PD and controls. The globus pallidus in PSP and the putamen in MSA-p were the most significant areas of atrophy to differentiate PSP, MSA-p and PD (AUC = 0.856, 0.832, respectively, p < 0.001). The R2 values in both structures increased in parallel with the extent of atrophy. They were negatively correlated with volumes in putamen (r = -0.777, p < 0.001) and globus pallidus (r = -0.409, p = 0.025) of MSA-p, and globus pallidus (r = -0.4, p = 0.043) of PSP. Voxel-based analysis identified higher R2 values in more severely atrophic sub-regions in these structures. We observed topographical differences of iron deposition as well as atrophy between MSA-p and PSP. Increased iron levels were related to the structural atrophy in basal ganglia. Our results imply that iron accumulation is likely an epiphenomenon of the degenerative process.

Oligodendroglial alpha-synucleinopathy and MSA-like cardiovascular autonomic failure: Experimental evidence

Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with limited symptomatic treatment options. Discrimination of MSA from other degenerative disorders crucially depends on the presence of early and severe cardiovascular autonomic failure (CAF). We have previously shown that neuropathologic lesions in the central autonomic nuclei similar to the human disease are present in transgenic MSA mice generated by targeted oligodendroglial overexpression of α-syn using the PLP promoter. We here explore whether such lesions result in abnormalities of heart rate variability (HRV) and circadian rhythmicity which are typically impaired in MSA patients.HRV analysis was performed in five month old transgenic PLP-α-syn (tg) MSA mice and age-matched wild type controls. Decreased HRV and alterations in the circadian rhythmicity were detected in the tg MSA group. The number of choline-acetyltransferase-immunoreactive neurons in the nucleus ambiguus was significantly decreased in the tg group, whereas the levels of arginine-vasopressin neurons in the suprachiasmatic and paraventricular nucleus were not affected. Our finding of impaired HRV and circadian rhythmicity in tg MSA mice associated with degeneration of the nucleus ambiguus suggests that a cardinal non-motor feature of human MSA can be reproduced in the mouse model strengthening its role as a valuable testbed for studying selective vulnerability and assessing translational therapies.

Topographical differences of brain iron deposition between progressive supranuclear palsy and parkinsonian variant multiple system atrophy

ObjectiveThere have been various studies showing increased iron levels in parkinsonian disorders. The purpose of this study was to demonstrate topographical differences of brain iron deposition between progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple system atrophy (MSA-p) with SWI images. MethodsA total of 11 patients with PSP, 12 with MSA-p, 15 with Parkinson's disease (PD), and 20 age-matched healthy controls underwent SWI of the brain. Mean phase shift values of the red nucleus (RN), substantia nigra (SN), head of the caudate nucleus (CN), globus pallidus (GP), putamen (PUT), and thalamus (TH) were calculated and compared between groups. A voxel-based analysis of the processed SWI was performed to determine topographical differences of iron-related hypointense signals in PUT, GP, and TH. ResultsPatients with PSP and MSA-p had significantly higher levels of iron deposition than control and PD groups. Comparing patients with PSP and MSA-p, differences were found in iron concentrations of the RN, SN, GP, and TH, which were higher in the PSP group. However, iron levels in the PUT were higher in the MSA group (p<0.05). The area under curve (AUC) indicated that the PUT was the most valuable nucleus in differentiating MSA-p from PSP and PD according to phase shift values (AUC=0.836). Meanwhile the GP (AUC=0.869) and TH (AUC=0.884) were the two most valuable nuclei in differentiating PSP from MSA-p and PD. Voxel-based analysis showed subregional differences in iron-related hypointense signals in the PUT, GP, and TH between MSA-p and PSP groups. Patients with MSA-p had significant increases of iron-related hypointense signals in the posterolateral PUT and adjacent lateral aspect of the GP, whereas the PSP group had increased hypodense signals in the anterior and medial aspects of the GP and TH. ConclusionOur data demonstrate that pathological iron accumulations are more prevalent and severe in PSP compared to MSA-p. The distribution of high-iron-content regions in this study reflects pathoanatomically relevant sites. This finding allows for the use of MRI-based brain iron mapping as a technique to indirectly identify pathological changes.

18F-FDG PET imaging in early diagnosis of multiple system atrophy

Objective To evaluate the feasibility of 18F-FDG PET/CT imaging in the early diagnosis of multiple system atrophy (MSA) and differentiation from early PD.Methods Five patients with MSA were included in this study.These patients had a disease duration of less than 2 years,predominantly with cerebellar dysfunction (MSA-C).Ten clinically confirmed PD patients with disease duration less than 3 years were also enrolled.All patients underwent 18F-FDG PET/CT imaging.To compare the metabolic features of these two diseases,SPM 5 software and t-test were used for image data analysis.The PD related pattern (PDRP) expression was calculated in all patients and the efficacy of the PDRP score in distinguishing early MSA from PD was evaluated.Results At the t-test level of P =0.01,all the 5 MSA patients displayed cerebellar hypometabolism ( t:-13.04 to -3.75 ) and 3 of them also had decreased metabolism in the putamen (t:-5.14 to -3.21 ).On the contrary,all PD patients showed cerebellar hypermetabolism (t:4.16 to 11.72) and normal metabolism in putamen.The PDRP scores in the PD group were significantly higher than those in the MSA group(ll.9±4.96vs -6.25±5.97,t=6.27,P＜0.01).Conclusions Cerebellar hypometabolism is the predominant FDG-PET feature of MSA-C,which may be used to distinguish it from early PD.Striatum may be involved in the early phase of MSA-C,displaying hypometabolism in putamen.The PDRP scores are also helpful in differentiating early phase MSA-C from early PD. Key words: Multiple system atrophy; Tomography, emission-computed ; Tomography,X-ray computed; Diagnosis, differential; Deoxyglucose

Is peripheral neuron degeneration involved in multiple system atrophy? A clinical and electrophysiological study

Lower motor neuron lesions are not among the characteristic features of multiple system atrophy (MSA), although electromyography (EMG) and autopsy studies revealed peripheral neuron abnormalities in some cases of MSA.The aim of the study was to evaluate subclinical involvement of the peripheral neuron in MSA using EMG and electroneurography (ENG). Material48 patients with clinically probable MSA (mean age 60.6years; 67% males) were included in the study and divided into subgroups, with predominant cerebellar (MSA-C) and parkinsonian signs (MSA-P). MethodsENG in ulnar, peroneal and sural nerves and EMG of the first interosseus dorsal and tibial anterior muscles were performed. ResultsAbnormal ENG in one nerve was recorded in 20.8% of patients, and in two nerves in another 20.8% of patients. The most frequent and significant findings were decreased compound motor action potential amplitudes in the ulnar nerve in the overall MSA group as well as in the MSA-P type as compared to controls. Abnormalities suggesting reinnervation was observed in 43 of 96 examined muscles (44.7%). In individual cases, neurogenic features were recorded in one muscle in 31.2% of patients and in two muscles in 29.1% of patients. ConclusionsSubclinical axonopathy in MSA is not frequent and is more pronounced in MSA with predominant parkinsonian signs. In MSA, neurogenic EMG abnormalities in muscles are more frequent than peripheral nerve lesions and as evidenced by increased motor unit potential amplitudes, could be considered a sign of anterior horn cell involvement and a hallmark of the “continuum” of neurodegeneration in MSA.

Network correlates of disease severity in multiple system atrophy

Multiple system atrophy (MSA), the most common of the atypical parkinsonian disorders, is characterized by the presence of an abnormal spatial covariance pattern in resting state metabolic brain images from patients with this disease. Nonetheless, the potential utility of this pattern as a MSA biomarker is contingent upon its specificity for this disorder and its relationship to clinical disability in individual patients. We used [(18)F]fluorodeoxyglucose PET to study 33 patients with MSA, 20 age- and severity-matched patients with idiopathic Parkinson disease (PD), and 15 healthy volunteers. For each subject, we computed the expression of the previously characterized metabolic covariance patterns for MSA and PD (termed MSARP and PDRP, respectively) on a prospective single-case basis. The resulting network values for the individual patients were correlated with clinical motor ratings and disease duration. In the MSA group, disease-related pattern (MSARP) values were elevated relative to the control and PD groups (p < 0.001 for both comparisons). In this group, MSARP values correlated with clinical ratings of motor disability (r = 0.57, p = 0.0008) and with disease duration (r = -0.376, p = 0.03). By contrast, MSARP expression in the PD group did not differ from control values (p = 1.0). In this group, motor ratings correlated with PDRP (r = 0.60, p = 0.006) but not with MSARP values (p = 0.88). MSA is associated with elevated expression of a specific disease-related metabolic pattern. Moreover, differences in the expression of this pattern in patients with MSA correlate with clinical disability. The findings suggest that the MSARP may be a useful biomarker in trials of new therapies for this disorder.