MSA-C Patients Research Articles

Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: A pilot study

ObjectivesMultiple system atrophy (MSA) is a neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in the central nervous system. The cause of MSA remains essentially unknown. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, apparently not related to MSA and was partially responsive to immunomodulatory therapy. Patients and methods28 euthyroid patients who fulfilled the diagnostic criteria for probable MSA, 11 with MSA-cerebellar type (MSA-C), 17 with MSA-parkinsonian type (MSA-P), 28 patients with Parkinson's disease (PD) and 26 normal euthyroid controls were tested the for serum levels of anti-thyroperoxidase antibodies (anti-TPO) and anti-thyroglobulin (Anti-TG) antibodies (Ab). ResultsThe laboratory results were statistically similar in all three groups, but 3 MSA-C patients had highly elevated anti-TPO Ab titers. ConclusionWe identified the presence of elevated anti-TPO levels in a small subgroup of MSA-C patients but neither in MSA-P or PD patients nor in healthy controls. These findings may suggest an autoimmune etiology in some cases of MSA-C.

Early clinical features of patients with progressive supranuclear palsy with predominant cerebellar ataxia

BackgroundPatients who develop progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) develop cerebellar ataxia as the initial and principal symptom, may be misdiagnosed as having multiple system atrophy with predominant cerebellar features (MSA-C). Therefore, we investigated the clinical signs and symptoms between PSP-C and MSA-C early in their disease course. MethodsWe reviewed the medical records of 15 consecutive patients with pathologically proven PSP-C (4) and MSA-C (11). We recorded the presence or absence of clinical features that developed within 2 years of disease onset. ResultsThe age at onset of PSP-C patients was older than that of MSA-C patients (p = 0.009). The frequencies of falls were higher in PSP-C patients than in MSA-C patients (p = 0.026). Additionally, the development of supranuclear vertical gaze palsy was higher in PSP-C patients than in MSA-C patients (p = 0.011), whereas the frequency of dysautonomia was lower in PSP-C patients than in MSA-C patients (p = 0.035). ConclusionsOlder onset, early falls, and supranuclear vertical gaze palsy without dysautonomia may predict the diagnosis of PSP-C in patients with late-onset sporadic cerebellar ataxia.

Skin temperature of the hand in multiple system atrophy and Parkinson's disease

AimA previous study on a small number of patients showed that low skin temperature of the hands, the so called “cold hands sign”, may be useful for distinguishing multiple system atrophy (MSA) from Parkinson's disease (PD). We have further investigated skin temperature of the hand in a larger number of patients. MethodsSkin temperature on the palm was measured in 50 MSA (11 MSA-P and 39 MSA-C patients) and 50 PD patients, and 25 normal healthy subjects. ResultsPalm skin temperature was significantly lower in MSA patients (32.0 ± 2.7 °C) than in controls (34.1 ± 0.9 °C, p = 0.0002), but was not different compared with the PD group (32.9 ± 1.8 °C, p = 0.06). Temperatures of <28 °C were observed in 3 MSA patients (6%) and none of the PD patients and controls. There was no significant difference in palm skin temperature between patients with and without orthostatic hypotension for each patient group, or between MSA-P and MSA-C patients. ConclusionThe cold hand (<28 °C) is a useful marker for distinguishing MSA from PD, but it is not common in MSA patients, and its sensitivity may be low for differentiating between MSA and PD.

No Difference in Sleep and RBD between Different Types of Patients with Multiple System Atrophy: A Pilot Video-Polysomnographical Study

Background. Patients with multiple system atrophy (MSA), similarly to patients with alpha-synucleinopathies, can present with different sleep problems. We sought to analyze sleep problems in the two subtypes of the disease MSA cerebellar type (MSA-C) and MSA parkinsonian type (MSA-P), paying special attention to REM sleep disturbances and periodic limb movements (PLMs). Methods. In the study we included 11 MSA-C and 27 MSA-P patients who underwent one night polysomnography. For the analysis, there were 37 valid polysomnographic studies. Results. Sleep efficiency was decreased in both groups (MSA-C, 64.27% ± 12.04%; MSA-P, 60.64% ± 6.01%). The PLM indices using standard measures, in sleep (PLMS) and while awake (PLMW), were high in both groups (MSA-C patients: PLMS index 72 ± 65, PLMW index 38 ± 33; MSA-P patients: PLMS index 66 ± 63, PLMW index 48 ± 37). Almost one-third of the MSA patients of both groups presented features of RLS on video-polysomnography. RBD was described in 8/11 (73%) patients with MSA-C and 19/25 (76%) patients with MSA-P (P = 0.849). Conclusion. Our results showed very similar polysomnographic results for both MSA-P and MSA-C patients as a probable indicator for the similar pathologic mechanism of the disease and especially of its sleep problems.

11 Attentional impairment in Multiple System Atrophy

Background Several studies have reported cognitive impairment in the Parkinsonian (MSA-P) and cerebellar (MSA-C) variants of Multiple System Atrophy, particularly in executive functions. This is attributed to a dysfunction of the cognitive loop linking the prefrontal cortex to basal ganglia. Since a few studies have investigated attentional functions in MSA patients, we assessed cognitive dysfunction and different aspect of attention in patients with MSA-C and MSA-P. Methods Seventeen MSA patients underwent a cognitive assessment of verbal/visual memory, language, visuo-spatial abilities and executive functions. The patients and 32 matched controls were presented with an experimental attentional task designed on Posner’s original Attention Network Test. The task provided three cue conditions (no-cue, temporal-cue, spatial-cue), two target conditions (congruent/incongruent) and two cue validity manipulations (valid/invalid-cue). Comparing reaction times in different experimental conditions allowed assessing the efficiency of the three different attentional components: Alerting, Orienting and Executive Control. Results Patients with MSA-P were impaired in executive functions, verbal memory and visuo-spatial abilities; MSAC patients in space and object perception tasks. MSA patients performed significantly worse than controls in attentional tasks with MSA-C patients showing more errors and longer RTs in incongruent target conditions. Conclusions MSA patients show specific cognitive impairments. MSA-C patients, in particular, are impaired in the attentional tasks. The greater impairment of Executive Control in these patients may be attributed to the widespread degeneration of cerebellum and cerebello-ponto-thalamo fibres projecting to medial areas of prefrontal cortex.

Hyperintense putaminal rim at 1.5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy

BackgroundHyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at 3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and the features which distinguish from HPR in MSA patients.MethodsAxial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C) were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher’s exact test, t-test, and one way analysis of variance were used to determine significance at corrected p < 0.05.ResultsHPR was observed in 38.5% of normal subjects. Age and gender predilection and laterality were not observed. In most cases, it occupied the full length or anterior half of the lateral margin of putamen, and was continuous throughout its length. Maximum transverse dimension was 2 mm. There was no association with hypointensity of nearby putamen. However, in MSA-P, HPR was located predominantly at the posterolateral aspect of putamen, and associated with putaminal atrophy. Discontinuity of HPR was more frequently observed in MSA-P. On visual analysis, the characteristics of HPR were similar between MSA-C patients and normal subjects. Patients with MSA of either type had significantly higher MD values of putamen than normal subjects.ConclusionsHPR can be observed in 38.5% of normal subjects at 1.5 T. Thin linear hyperintensity without discontinuity, occupying the full length or anterior half of the lateral margin of the putamen, is suggestive of “normal.” In doubtful cases, measurement of the MD values of nearby putamen may be valuable.

Progression of Idiopathic Late Onset Cerebellar Ataxia (S12.006)

Objective: To analyze the follow-up of idiopathic late onset cerebellar ataxia (ILOCA) patients. Background ILOCA patients represent a group of neurodegenerative diseases of unknown cause affecting the cerebellum and its afferent and efferent connections. Design/Methods: Clinical and laboratory observations of the course of 50 adult patients initially evaluated in an cerebellar ataxia outpatient clinic over 20 years, with a diagnosis of ILOCA, and followed up regularly. The presence of REM sleep behavior disorder (RBD) was evaluated as probable RBD, based on clinical validated criteria, or definite RBD, based on polysomnographic confirmation. Results: From a total of 50 patients with ILOCA (excluding all patients with acquired or genetically defined cerebellar ataxia), 24 subsequently developed criteria for MSA type-C. 26 patients remained with the diagnosis of ILOCA, among them 8 with a probable diagnosis of late cerebellar atrophy of Marie-Foix-Alajouanine syndrome (MFAS). The group of patients with late cerebellar atrophy of MFAS had an older mean age (72.8 years) than MSA-C patients (59.5 years). Neurological examination, including a thorough eye movement assessment did not differentiate patients with MSA-C and ILOCA. Clinically or definite RBD was diagnosed in 46 % of patients. However, patients who developed MSA type C had a highly percentage of probable and definite previously diagnosis of RBD (83.4%). On the other hand, among patients with ILOCA, the percentage of RBD was significantly lower (11.5%, p Conclusions: In this Brazilian series of ILOCA patients, MSA-C was clinically diagnosed in 48 % of cases and 52 % remained with the diagnosis of ILOCA, including a 12 % with the diagnosis of late cerebellar atrophy of MFAS. RBD diagnosis, either clinical or polysomnographic should included as an important tool in the differentiation of MSA type C and ILOCA. Disclosure: Dr. Teive has nothing to disclose. Dr. Munhoz has nothing to disclose. Dr. Arruda has nothing to disclose. Dr. Werneck has nothing to disclose.

CSF Biomarkers in Spinocerebellar Ataxias (P05.018)

Objective: To identify potential biomarkers in the cerebrospinal fluid (CSF) of patients with spinocerebellar ataxia (SCA) 1, SCA2, SCA6, and multiple system atrophy of the cerebellar type (MSA-C). Background Levels of proteins such as α-synuclein, tau, and DJ-1 have shown promise as potential type-specific and stage-specific bioimarkers of several neurodegenerative diseases, including Parkinson9s, Alzheimer9s, multiple sclerosis, and ALS. DJ-1 has recently been shown to be involved in oxidative stress and to be elevated in the early stages of Parkinson9s. α-synuclein is thought to be involved in vesicle trafficking and is decreased in the CSF of Parkinson9s patients. Tau is a general marker of neuroaxonal damage elevated in Alzheimer9s, ALS, and multiple sclerosis. Limited to no biomarker data has been previously published in regards to ataxia disorders. Design/Methods: The CSF samples were obtained for this study from 26 patients: 5 diagnosed with SCA1, 6 with SCA2, 5 with SCA6, 5 with MSA-C, and 5 controls with no neurological pathology. CSF was analyzed using commercial enzyme-linked immunoabsorption assays (ELISAs) to determine protein concentrations of α-synuclein, tau, and DJ-1. Statistical analysis was performed using a Mann-Whitney U nonparametric test with appropriate post-hoc Bonferroni corrections. Results: DJ-1 levels were unchanged in all the disease states. Levels of α-synuclein were elevated only in SCA-2 patients (p=0.004) at 0.6965 ng/mL vs. 0.4312 ng/mL in controls. Tau protein was elevated in both MSA-C (p=0.004) and SCA2 (p=0.002) patients at 76.117 pg/mL and 106.634 pg/mL respectively as compared to 44.154 pg/mL in the controls. Conclusions: Elevated levels of both tau and α-synuclein in SCA2 and none of the other SCAs examined indicate a possible differentiation between diseases that present in a clinically similar manner. Additionally, as very little is known about MSA-C, elevated levels of tau could provide insight into pathogenesis. Supported by: National Ataxia Foundation, JayD Schlueter Fund. Disclosure: Dr. Brouillette has nothing to disclose. Dr. Gomez has nothing to disclose.

Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type (MSA-C) using three-dimensional gyrification index analysis

Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative neurological disease of the central nervous system. This study employed a method named, "surface-based three-dimensional gyrification index" (3D-GI) to quantify morphological changes in normal cerebellum (including brainstem) and atrophied cerebellum, in patients with MSA-C. We assessed whether 3D-GI can exclude gender and age differences to quantify cerebellum and brainstem atrophy more accurately. Sixteen healthy subjects and 16 MSA-C patients participated in this study. We compared 3D-GI values and volumes in the cerebellum, based on T1-weighted MR images. We also compared the images of reconstructed 3D cerebellum gray matter (3D-CBGM) and cerebellum white matter (3D-CBWM) to detect the atrophied cerebellar region in MSA-C patients. The 3D-GI values were in a stable range with small variances, exhibiting no gender effect and no age-related shrinkage. Significantly lower 3D-GI values were exhibited in both CBGM and CBWM of the MSA-C patients compared with healthy subjects, even in the early phases of the disease. Decreases in 3D-GI values indicated the degeneration of the cerebellar folding structure, exactly reflecting the morphological changes in cerebellum. The 3D-GI method based on CBGM resulted in superior discriminative accuracy compared with the CBGM volumetric method. Using the two-dimensional 3D-GI values, the K-means classifier can evidently discriminate the MSA-C patients from healthy subjects.

Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells

The aims of this study were to observe the safety and effectiveness of umbilical cord mesenchymal stromal cells (UC-MSC) in the treatment of spinocerebellar ataxia (SCA) and multiple system atrophy-cerebellar type (MSA-C). From October 2009 to September 2010, 14 cases of SCA and 10 cases of MSA-C were given UC-MSC by weekly intrathecal injection, at a dose of 1 × 10(6)/kg four times as one course. All the patients received one course of treatment, except three patients who received two courses. The movement ability and quality of daily life were evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and Activity of Daily Living Scale (ADL) and the scores compared with those before cell therapy. A follow-up of 6-15 months was carried out for all of the patients. The results showed that the ICARS and ADL scores were significantly decreased 1 month after treatment (P < 0.01). The symptoms, including unstable walking and standing, slow movement, fine motor disorders of the upper limbs, writing difficulties and dysarthria, were greatly improved except for one patient, who had no response. The observed side-effects included dizziness (four patients), back pain (two cases) and headache (one case), which disappeared within 1-3 days. During the follow-up, 10 cases remained stable for half a year or longer, while 14 cases had regressed to the status prior to the treatment within 1-14 months (an average of 3 months). Intrathecal injection of UC-MSC is safe and can delay the progression of neurologic deficits for SCA and MSA-C patients.

Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C)

Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ((123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([(123)I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [(123)I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [(123)I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.

Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone

BackgroundPartial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT) images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM) to SPECT.MethodsAfter linear spatial normalization of brain perfusion SPECT using 99mTc-ethyl cysteinate dimer (99mTc-ECD) to a Talairach space, high-dimension-warping was done using an original 99mTc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2) between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C) patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images.ResultsSPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99mTc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution.ConclusionsThe present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT

Morphometry MRI in the differential diagnosis of parkinsonian syndromes

This study evaluates the diagnostic value of morphometric magnetic resonance imaging (MRI) in the differential diagnosis among Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). We studied 21 PD cases, 11 MSA-c, 8 MSA-p and 20 PSP cases. Midbrain area (Ams), pons area (Apn), middle cerebellar peduncle (MCP) and superior cerebellar peduncle (SCP) were measured using MRI. Comparisons were made between PD, MSA-p, MSA-c and PSP. Apn, MCP and SCP morphometry dimensions presented differences among groups. Ams below 105 mm(2) and SCP smaller than 3 mm were the most predictive measures of PSP (sensitivity 95.0 and 80.0%, respectively). For the group of MSA-c patients, Apn area below 315 mm(2) showed good specificity and positive predictive value (93.8% and 72.7%, respectively). In conclusion, dimensions and cut off values obtained from routine MRI can differentiate between PD, PSP and MSA-c with good sensitivity, specificity and accuracy.

Classification of Cerebellar Atrophy Using Voxel-based Morphometry and SPECT with an Easy Z-score Imaging System

With conventional MRI and single-photon emission computed tomography (SPECT), accurate diagnosis and precise classification of cerebellar atrophy are often difficult. The objective was to verify the utility of MRI voxel-based morphometry (VBM) in combination with SPECT using easy Z-score imaging (eZIS) for diagnosing and classifying cerebellar atrophy. We assessed gray matter atrophy using VBM and blood perfusion using SPECT with eZIS in fifteen patients with different types of cerebellar atrophy, such as the cerebellar variant of multiple system atrophy (MSA-C), spinocerebellar ataxia type 3 (SCA3), SCA6, and autoimmune cerebellar ataxia (AICA). In all five MSA-C patients, VBM imaging showed atrophy of the brainstem, the entire cerebellar vermis, and the cerebellar hemispheres, while SPECT using eZIS showed reduced perfusion in the same regions. Regarding SCA3, brainstem atrophy and reduced perfusion were recognized in two of the four patients, but none exhibited abnormal findings in the posterior lobe of the cerebellar vermis. SPECT showed that all four patients had obviously reduced perfusion in the anterior lobe of the vermis, but VBM demonstrated that there was no obvious atrophy of gray matter in any patient, meaning that the results of SPECT and VBM contradicted each other completely. All SCA6 and AICA patients exhibited atrophy and reduced perfusion in the cerebellar hemispheres but not in the brainstem. Only one AICA patient exhibited atrophy and reduced perfusion of the entire cerebellar vermis. VBM clearly showed characteristic gray matter atrophy in the cerebellum and brainstem in different pathological conditions, thus indicating its high degree of utility in diagnosing and classifying cerebellar atrophy in combination with SPECT using eZIS.

Fractal dimension analysis for quantifying cerebellar morphological change of multiple system atrophy of the cerebellar type (MSA-C)

Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative neurological disease of the central nervous system. This study aims to demonstrate that the morphological changes of cerebellar structure, specifically, the cerebellum white matter (CBWM) and cerebellum gray matter (CBGM) from T1-weighted magnetic resonance (MR) images, can be quantified by three-dimensional (3D) fractal dimension (FD) analysis, which is a measure of complexity. Twenty-three MSA-C patients and twenty-one normal subjects participated in this study. The results of this study show that MSA-C patients presented significantly lower FD values compared to the control group, and that morphological change in the CBWM dominates the cerebellar degeneration. In addition, the FD analysis method is superior to conventional volumetric methods in quantifying the structural changes of WM and GM because it exhibits smaller variances and less gender effect. Since a decrease of cerebellar FD value indicates degeneration of the cerebellar structure, this study further suggests that the morphological changes of cerebellar structures (CBGM and CBWM) can be characterized by FD analysis.

Reduced Fractional Anisotropy in Early‐Stage Cerebellar Variant of Multiple System Atrophy

In patients with the cerebellar variant of multiple system atrophy (MSA-C), reduced fractional anisotropy (FA) has been reported in several brain areas. However, since previous studies have employed predetermined regions of interest (ROI), the brain areas showing the earliest alterations in FA are unknown. The sensitivity of detecting early-stage MSA-C and the time course of the FA reduction are also unknown. The purpose was to address these issues to determine the diagnostic value of FA for early diagnosis. Twenty-one patients with MSA-C were investigated. Voxel-based FA analysis and morphometry were used to detect the differences between early-stage MSA-C and normal controls. An ROI-based FA analysis was also used to clarify the temporal profile. From the early-stage, MSA-C patients exhibited reduced FA and white matter atrophy in the middle cerebellar peduncle, the inferior cerebellar peduncle, and the ventral pons. The FA of these areas decreased rapidly during the first few years after onset, after which a rather gradual reduction occurred. The receiver operating characteristics analysis revealed a high sensitivity and specificity for discriminating early MSA-C from normal controls. FA measurement could potentially be used to make an early diagnosis and monitor progression in MSA-C patients.

Autonomic dysfunction in different subtypes of multiple system atrophy

Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA-C and 26 with MSA-P in comparison with 27 age- and sex-matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA-P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA-C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes.

Cortical metabolic changes in the cerebellar variant of multiple system atrophy: A voxel-based FDG-PET study in 41 patients

In addition to neuronal loss in the cerebellum and basal ganglia, recent imaging studies have suggested that cortical involvement may be more extensive in patients with MSA. In this study, we focused on cortical metabolic patterns in 41 patients with MSA-C and 30 controls, using statistical parametric mapping analysis to evaluate whether metabolic derangement in MSA-C patients involved the cortical area and correlated cerebral metabolism with clinical parameters. In patients with MSA-C, SPM analysis revealed that, apart from the expected reduction of FDG-uptake in brainstem–cerebellar area, there was a significant hypometabolism in widespread frontal cortex, including inferior orbitofrontal, rectus, middle and superior frontal, and superior mesiofrontal extending to cingulum, and left inferior parietal cortex. In a subgroup analysis of MSA-C patients, metabolic derangement in the cerebral cortex was visible even in the early stages of MSA-C. In advanced stages, the metabolic derangement tended to evolve into the rostral brainstem and into other cortical areas, including left inferior frontal cortex and right inferior orbitofrontal, right anterior and middle cingulate, and anterior portion of superior mesiofrontal gyri. In correlation analysis, reduced FDG-uptake in orbitofrontal area was most significantly correlated with disease severity and duration, followed by the medial frontal, the dorsal portion of the midbrain, and the cerebellum. Our study demonstrated that there were widespread areas of decreased metabolism in the cerebral cortex and, as the disease progressed, the pattern of metabolic derangement tended to evolve into other frontal areas without significant changes in cerebellar metabolism, suggesting that reduced FDG-uptake in cortical area may be associated with the primary disease process.

Comparison of brain MRI and 18F‐FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease

To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.

CSF hypocretin-1 levels are normal in multiple-system atrophy

Sleep disturbances occur in 70% of the patients with multiple system atrophy (MSA). Disturbances of the hypothalamic hypocretin neurotransmission have been suggested as a possible cause. Since a systematic study of CSF hypocretin-1 levels in MSA has not yet been performed, we analysed CSF hypocretin-1 concentrations in 6 MSA-P and 6 MSA-C patients and 11 age-matched controls. We did not observe any differences from control values.