Diagnosis Of MSA Research Articles

Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists’ perspectives

BackgroundMultiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists’ current practices and experiences in delivering the diagnosis of MSA.MethodsWe conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique.ResultsAmong the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA.ConclusionsOur findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient’s personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term “sudden death” in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement.

Comparison of mean diffusivity, R2* relaxation rate and morphometric biomarkers for the clinical differentiation of parkinsonism

IntroductionQuantitative biomarkers for clinical differentiation of parkinsonian syndromes are still lacking. Our aim was to evaluate the value of combining clinically feasible manual measurements of R2* relaxation rates and mean diffusivity (MD) in subcortical regions and brainstem morphometric measurements to improve the discrimination of parkinsonian syndromes. MethodsTwenty-two healthy controls (HC), 25 patients with Parkinson's disease (PD), 19 with progressive supranuclear palsy (PSP) and 27 with multiple system atrophy (MSA, 21 with the parkinsonian variant -MSAp, 6 with the cerebellar variant -MSAc) were recruited. R2*, MD measurements and morphometric biomarkers including the midbrain to pons area ratio and the Magnetic Resonance Parkinsonism Index (MRPI) were compared between groups and their diagnostic performances were assessed. ResultsMorphometric biomarkers discriminated better patients with PSP (ratio: AUC 0.89, MRPI: AUC 0.89) and MSAc (ratio: AUC 0.82, MRPI: AUC 0.75) from other groups. R2* and MD measurements in the posterior putamen performed better in separating patients with MSAp from PD (R2*: AUC 0.89; MD: AUC 0.89). For the three-class classification “MSA vs PD vs PSP”, the combination of MD and R2* measurements in the posterior putamen with morphometric biomarkers (AUC: 0.841) outperformed each marker separately. At the individual-level, there were seven discordances between imaging-based prediction and clinical diagnosis involving MSA. Using the new Movement Disorder Society criteria for the diagnosis of MSA, three of these seven patients were clinically reclassified as predicted by quantitative imaging. ConclusionCombining R2* and MD measurements in the posterior putamen with morphometric biomarkers improves the discrimination of parkinsonism.

Loss of putative GABAergic neurons in the ventrolateral medulla in multiple system atrophy.

Multiple system atrophy (MSA) is associated with disturbances in cardiovascular, sleep and respiratory control. The lateral paragigantocellular nucleus (LPGi) in the ventrolateral medulla (VLM) contains GABAergic neurons that participate in control of rapid eye movement (REM) sleep and cardiovagal responses. We sought to determine whether there was loss of putative GABAergic neurons in the LPGi and adjacent regions in MSA. Sections of the medulla were processed for GAD65/67 immunoreactivity in eight subjects with clinical and neuropathological diagnosis of MSA and in six control subjects. These putative GABAergic LPGi neurons were mapped based on their relationship to adjacent monoaminergic VLM groups. There were markedly decreased numbers of GAD-immunoreactive neurons in the LPGi and adjacent VLM regions in MSA. There is loss of GABAergic neurons in the VLM, including the LPGi in patients with MSA. Whereas these findings provide a possible mechanistic substrate, given the few cases included, further studies are necessary to determine whether they contribute to REM sleep-related cardiovagal and possibly respiratory dysregulation in MSA.

Identification of a pre-possible multiple system atrophy phase.

ObjectivesA pre‐possible multiple system atrophy (MSA) phase, that is, the period between symptom onset and satisfying the second consensus diagnostic criteria for possible or probable MSA, may exist. The aim of the study was to identify the pre‐possible MSA phase and to pursue the earlier diagnosis of MSA.Materials & MethodsWe reviewed 52 patients with a clinical diagnosis of MSA and 430 patients showing any signs of parkinsonism, sporadic cerebellar ataxia, or autonomic failure with other clinical diagnoses.ResultsThe pre‐possible MSA phase was noted in 35 patients with a clinical diagnosis of MSA and 13 patients with other clinical diagnoses. During this phase, 16 patients presented with autonomic features first, while they presented later in 32 patients. Between these patients, there was no significant difference regarding parkinsonian, cerebellar features, levodopa response, or Babinski sign with hyperreflexia. Comparisons by autonomic features or autonomic function tests could not be performed due to the small number of patients. “Atrophy on magnetic resonance imaging of the putamen, middle cerebellar peduncle, pons, or cerebellum” and “new or increased snoring” showed high positive predictive values for MSA.ConclusionA pre‐possible MSA phase exists. Improved earlier diagnosis of MSA depends on the sensitivity and positive predictive value of autonomic features or autonomic function tests and on the sensitivity of “atrophy on magnetic resonance imaging of the putamen, middle cerebellar peduncle, pons, or cerebellum” and “new or increased snoring” during the pre‐possible MSA phase.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients: A case control study.

BACKGROUNDMultiple system atrophy (MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15 (GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIMTo determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease (PD) patients and healthy controls.METHODSA case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTSSerum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively).CONCLUSIONSerum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Cerebrovascular pathology and misdiagnosis of multiple system atrophy: An autopsy study

BackgroundMultiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by a combination of dysautonomia, parkinsonism, and cerebellar ataxia. Other disorders can mimic MSA, but it is unknown whether cerebrovascular pathology, so-called “vascular parkinsonism,” can mimic MSA. This study aimed to determine the clinicopathological features and red flags for vascular parkinsonism masquerading as MSA. MethodsUsing a brain bank database, we screened 270 patients with an antemortem diagnosis of MSA, who did not have pathologic evidence of MSA, but rather cerebrovascular pathology, including leukoencephalopathy, lacunar infarcts, and microinfarcts. Histologic sections from the neocortex, basal ganglia, thalamus, brainstem, and cerebellum were reviewed. Medical records were reviewed to characterize the clinical features. The probability of a clinical diagnosis of MSA was assigned retrospectively, guided by current consensus criteria. ResultsFour patients had cerebrovascular pathology without neurodegenerative processes. Chronic ischemic changes in periventricular white matter, subcortical leukoencephalopathy, lacunar infarcts, or microinfarcts were detected in basal ganglia of all patients. Cerebrovascular pathology that might contribute to autonomic failure was not identified. Clinically, two patients were diagnosed with possible MSA-parkinsonism, one with probable MSA-parkinsonism, and one with possible MSA-cerebellar type; however, they also had one or more non-supporting features of MSA (e.g., onset >75-years of age, dementia), vascular risk factors, and other etiologies (e.g., autonomic neuropathy) that could cause autonomic failure. ConclusionsWhen combined with cerebrovascular risk factors and comorbidities, cerebrovascular pathology may masquerade as MSA. The important lesson from this study is that the diagnosis of MSA requires exclusion of other causes, including cerebrovascular disease.

Is There a Difference in Autonomic Dysfunction Between Multiple System Atrophy Subtypes?

Autonomic dysfunction forms the diagnostic cornerstone in MSA. Data are limited on autonomic dysfunction differences between the two subtypes, MSA-C and MSA-P. To assess autonomic dysfunction in MSA subtypes and Parkinson's disease (PD) and compare it to healthy controls. We conducted a cross-sectional study. A validated questionnaire (Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction; SCOPA-AUT) was used for symptom screening. Cardiovascular autonomic testing included deep breathing (change in heart rate, E: I ratio), Valsalva ratio, diastolic blood pressure (BP) rise (hand grip, cold pressor), and postural (tilt, 30:15 ratio) tests. Disease severity was assessed by the Unified MSA Rating Scale (UMSARS), H & Y stage, and International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating scale part III. MSA-P (48 subjects; age, 63.6 ± 9.7 years; UMSARS, 45.0 ± 16.5), MSA-C (52 subjects; age, 58.0 ± 8.1 years; UMSARS, 44.0 ± 12.8), PD (50 subjects; age, 57.6 ± 6.7 years), and healthy controls (50 subjects; age, 58.0 ± 8.0 years) were enrolled. MSA patients had higher SCOPA-AUT scores in gastrointestinal, urinary, cardiovascular, and sexual domains than controls and in gastrointestinal, urinary, and cardiovascular domains compared to PD. The two MSA subtypes did not differ in autonomic dysfunction. Heart-rate change on tilt and deep breathing, and diastolic BP rise on cold pressor test, differed significantly between MSA and PD patients. Autonomic dysfunction symptomatology and cardiovascular autonomic tests were similar between MSA-P and MSA-C patients. Autonomic symptoms were more prominent in MSA than PD. Emphasis on these domains may improve likelihood of accurate clinical diagnosis of MSA at earlier stages.

Difficulties of differential diagnosis in multisystem atrophy

Multiple systemic atrophy.(MSA) is a progressive neurodegenerative disease with a poor prognosis and unknown etiology, which belongs to the “atypical parkinsonism” group of diseases. Currently, the diagnosis of MSA is difficult and at the present stage remains predominantly clinical. But, despite the fact that no effective treatment has been developed, timely diagnosis and symptomatic therapy can improve the patient’s quality of life. The article presents a clinical observation of a patient with MSA, a feature of which was the combination of MSA with vascular pathology, which greatly complicated and delayed the diagnosis of MSA.

Reproducible metabolic topographies associated with multiple system atrophy: Network and regional analyses in Chinese and American patient cohorts

PurposeMultiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson's disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts. MethodsWe included 18F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnosis among moderate- and early-stage MSA, PSP or PD patients and clinical correlations with disease severity. Regional metabolic differences were detected using statistical parameter mapping analysis. MSA-related network and regional topographies of metabolic abnormality were cross-validated between the Chinese and American cohorts. ResultsWe generated a highly reliable MSAPRP characterized by decreased loading in inferior frontal cortex, striatum and cerebellum, and increased loading in sensorimotor, parietal and occipital cortices. MSAPRP scores discriminated between normal, MSA, PSP and PD subjects and correlated with standardized ratings of clinical stages and motor symptoms in MSA. High similarities in MSAPRPs, network scores and corresponding maps of metabolic abnormality were observed between two different cohorts. ConclusionWe have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.

Dopamine transporter imaging for the diagnosis of multiple system atrophy cerebellar type

IntroductionThe added value of dopamine transporter SPECT (DAT-SPECT) for the diagnosis of “possible” multiple system atrophy of the cerebellar type (MSA-C) remains unknown. MethodsWe reviewed retrospectively the charts of 128 consecutive patients with a clinical diagnosis of MSA-C who were seen between 2007 and 2016 at the French Reference Center for MSA. The main objective was to evaluate the proportion of patients for whom the diagnosis of “possible” MSA-C was made because of a positive DAT-SPECT. ResultsSeventy-eight MSA-C patients had at least one DAT-SPECT. Fifty-nine of them were considered for the final analysis. In these, 22 had “possible” MSA-C and 23 “probable” MSA-C before DAT-SPECT, while 14 did not reach diagnosis criteria at that time. In those with “possible” MSA-C, DAT-SPECT was positive in 64%. In patients with “probable” MSA-C, 83% showed nigrostriatal denervation. Six out of 14 (43%) received a diagnosis of “possible” MSA-C because of positive DAT-SPECT. These patients had mean disease duration of 2.3 years at the time of DAT-SPECT compared to 3.5 years of the entire cohort of MSA-C patients with DAT-SPECT. Of the eight remaining, one had positive DAT-SPECT but also pons atrophy on magnetic resonance imaging, and seven progressed to “probable” MSA based on clinical features. ConclusionOur results suggest that DAT-SPECT significantly contributes to the diagnosis of “possible” MSA-C (43% of patients not reaching consensus diagnosis criteria before DAT-SPECT). DAT-SPECT seems especially useful in patients with shorter disease duration, while a negative result does not exclude a diagnosis of MSA.

Clinical correlates of decreased plasma coenzyme Q10 levels in patients with multiple system atrophy

IntroductionMultiple system atrophy (MSA) is a progressive neurodegenerative disease. Recent studies revealed decreased coenzyme Q10 (COQ10) levels in the cerebellum and blood samples of MSA patients. But few studies focused on the associations of COQ10 with the clinical symptoms of MSA. In this study, we aimed to quantify plasma COQ10 and characterize its association with clinical features. MethodsWe recruited 40 patients with MSA, 30 patients with Parkinson's disease (PD), and 30 healthy participants. Plasma COQ10 was quantified by UPLC-MS. The basic demographic data, motor symptoms, and non-motor symptoms were also assessed. ResultsPlasma COQ10 levels were significantly different in MSA, PD, and controls (P = 0.001). Post-hoc analysis revealed plasma COQ10 levels in MSA patients were lower than that in controls after adjusting for age, gender, and total cholesterol (P = 0.001). COQ10 levels differentiated MSA patients from controls with modest accuracy (P = 0.001). A sensitivity of 40% and a specificity of 97.5% was calculated with the receiver operating characteristic curve. However, COQ 10 levels did not discriminate between the MSA and PD groups (P = 0.07). Plasma COQ10 levels were correlated with the severity of motor symptoms only in MSA-C patients (b = −0.025, P = 0.009). ConclusionThe association between decreased COQ10 levels and the severity of motor symptoms in MSA-C patients promotes further research. Plasma COQ10 levels alone may not be a reliable MSA diagnostic biomarker, and cannot be considered a useful biomarker in the differential diagnosis of MSA vs PD.

Sleep Abnormalities in MultipleSystem Atrophy.

The purpose of this review was to explore the different sleep disorders associated with MSA, their mechanisms, and their treatments. Stridor is a red flag for the diagnosis of MSA. Recent findings show that its presence in early stage of the disease is associated with a reduction in life expectancy. Its management should be fast and adapted. Its treatment with continuous positive airway pressure or tracheostomy is efficacious. Sleep disorders in MSA are frequent and severe combining insomnia, daytime sleepiness, restless legs syndrome (RLS), REM sleep behavior disorder (RBD), and sleep disordered breathing (SDB). Sleep recordings confirm these disorders. Mechanisms involved in these disorders are complex associating (a) lesions of the pathways regulating sleep and wake or mood but also controlling movement, (b) iatrogenic effects of the treatments, and (3) consequences of the motor or dysautonomic symptoms. RBD prevalence is very high at the beginning of the motor symptoms but then seems to disappear.

CSF biomarkers β-amyloid, tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes

IntroductionDifferential diagnosis of Parkinson-plus patients (PSP, CBD, MSA) and Parkinson's disease (PD) patients is often not straightforward, particularly in atypical cases or at the initial stages of the diseases. Classic CSF biomarkers (amyloid-beta – Aβ42, tau protein – τT and phosphorylated tau protein – τP-181) are established biomarkers in the diagnosis of Alzheimer's disease (AD). CSF a-synuclein (α-syn) has emerged as a promising biomarker in patients with Parkinsonism. The aim of this study was to analyze the CSF biochemical profile of patients with Parkinsonism. MethodsWe analyzed the CSF biomarker profile (Aβ42, τT, τP-181, α-syn) and all relevant ratios in 68 patients with Parkinsonism (19 PSP, 15 MSA, 17 CBD, 17 PD) and 18 controls, diagnosed by latest established diagnostic criteria. ResultsCBD patients exhibited elevated τT and decreased Aβ42 compared to the other groups. Five CBD, one PSP patient and one control had a typical AD CSF profile. After exclusion of these patients, the τT/Aβ42 ratio was significantly elevated in MSA patients compared to PD patients and provided excellent specificity and adequate sensitivity in their differential diagnosis. ConclusionCSF biochemical profile analysis is important in distinguishing AD patients with a CBS phenotype from non-AD CBS patients. The τT/Aβ42 ratio is useful in the differential diagnosis of MSA from PD.

Rapport de causalité entre le syndrome de la pince aorto-mésentérique et l’anorexie mentale. À propos d’un cas

IntroductionThe mesenteric artery syndrome (MSA) is a rare diagnosis. It is defined by the compression of the third portion of the duodenum between the superior mesenteric artery and aorta. Anorexia is an eventual aetiology among several others. The clinical symptoms of MSA and anorexia may be confused. In fact, the anorexia may be responsible for a MSA and the MSA with post-prandial abdominal pain, early satiety and bilious vomiting may be responsible for a loss of weight. ObservationWe report the case of a 29-year-old patient with an antecedent of a surgical treatment for a MSA who still presents a loss of weight and vomiting. An analysis of her clinical presentation reveals that she already presented signs of anorexia before the diagnosis of MSA. Physical and mental examination shows a patient with a BMI at 15, self-scrutiny, perfectionism, denial and food exclusion. It seems to us that this patient already presented anorexia and a nutritional treatment might have avoided the surgery. Now, we leaded her toward a psychotherapy. ConclusionThe mesenteric artery syndrome must be known by the healthcare professionals so as to avoid unnecessary surgical treatment.

Incidence and prevalence of multiple system atrophy: a nationwide study in Iceland

BackgroundMultiple system atrophy (MSA) is a neurodegenerative disorder characterised by autonomic dysfunction with parkinsonism (MSAp) or cerebellar (MSAc) symptoms. At autopsy, α-synuclein inclusions in glial cells of the brain are...

Profile of multiple system atrophy in Moroccan patients attending a movement disorders outpatient clinic in Rabat university hospital

IntroductionMultiple system atrophy (MSA) is a sporadic and rapidly progressive neurodegenerative disorder of poor prognosis, characterised clinically by any combination of parkinsonian, autonomic, cerebellar, or pyramidal signs. We report our experience in movement disorders consultation concerning the clinical presentation and the course of MSA in Moroccan patients. MethodsA retrospective review of the medical records of 17 patients with diagnosis of MSA seen in our outpatient clinic from January 2007 to December 2010. ResultsIn our 17 patients, 76.5% were men and the mean age of onset was 52±9 years. MSA-P was the major clinical phenotype (82.4%). Eleven patients (64.7%) were classified as having probable MSA and six patients (35.3%) as possible MSA. Dysautonomic features were detected in all patients; urinary symptoms were found in 76.5% of cases and orthostatic hypotension in 64.7%. Treatment regimen included l-Dopa with a mean daily dose of 621.4±346.8mg/day and symptomatic treatment of dysautonomia. The mean duration of disease evolution was of 4.7±1.9 years. DiscussionOur results show a male predominance and an early age of disease onset. MSA-P was the predominant subtype. Our results are similar to the European MSA series. ConclusionMulticentre studies are needed to better characterise MSA in Morocco given the rarity of this disease.

MRI-based volumetric differentiation of sporadic cerebellar ataxia

The term idiopathic cerebellar ataxia (IDCA) designates a variety of cerebellar syndromes that may present with a purely cerebellar syndrome (IDCA-C) or with additional extracerebellar features (IDCA-P). Multiple system atrophy is also a sporadic neurodegenerative disorder of unknown origin that may cause prominent cerebellar symptoms (MSA-C). The final neuropathological answer to the question whether IDCA-P and MSA-C represent different varieties of one disease or two distinct entities is still lacking. Three-dimensional MRI-based volumetry allows morphological investigations intra vitam. Volumetric analysis of cerebellum, brainstem and basal ganglia was therefore performed in 46 patients with sporadic cerebellar ataxia and 16 age-matched healthy controls. Patients with dementia were excluded from the study since cognitive impairment is an exclusion criterion for the diagnosis of MSA. Cerebellar patients were clinically divided into two groups: 33 patients with multiple system atrophy with prominent cerebellar symptoms (MSA-C) and 13 patients with extracerebellar features not corresponding to MSA-C (IDCA-P). There was evidence for substantial cerebellar atrophy in both cerebellar groups while additional brainstem atrophy was significantly more pronounced in MSA-C patients. Absolute caudate and putamen atrophy was found to be restricted to single MSA-C individuals while group comparisons of mean volumes did not yield significant differences from controls. Based on the volumetric data, diagnosis could be correctly predicted in 94% of control, 82% of MSA-C and 100% of IDCA-P individuals. The finding of specific imaging characteristics strengthens (i) the value of MRI volumetry in separating MSA-C from other types of sporadic cerebellar ataxia, and (ii) the hypothesis of two independent neurodegenerative disorders in MSA-C and IDCA-P.

Routine MRI for the differential diagnosis of Parkinson's disease, MSA, PSP, and CBD.

We assessed the usefulness of routine MRI for the differential diagnosis of Parkinson's disease (PD) with "atypical" parkinsonian syndromes in everyday clinical practice. We studied routinely performed MRI in PD (n = 32), multiple system atrophy (MSA, n = 28), progressive supranuclear palsy (PSP, n = 30), and corticobasal degeneration (CBD, n = 26). From a preliminary analysis of 26 items, 4 independent investigators rated 11 easily recognizable MRI pointers organized as a simple scoring system. The frequency, severity and inter-rater agreement were determined. The total severity score was subdivided into "cortical", "putaminal", "midbrain", and "pontocerebellar" scores. The frequency of putaminal involvement (100%) and vermian cerebellar atrophy (45%) was significantly higher in MSA, but that of cortical atrophy (50%), midbrain atrophy and 3(rd) ventricle enlargement (75%) was higher in PSP and CBD. The median total score fairly differentiated "atypical" parkinsonian syndromes from PD (positive predictive value-PPV-90%). However, the median total score was unable to differentiate atypical parkinsonian syndromes each other. The "cortical" score distinguished CBD and PSP from MSA with a fair PPV (>90%). The PPV of the "putaminal" score was high (70%) for the differential diagnosis of MSA with PSP and CBD. The "midbrain" score was significantly higher in PSP and CBD compared to MSA. These results are in accordance with the underlying pathology found in these disorders and demonstrate that a simple MRI scoring procedure may help the neurologist to differentiate primary causes of parkinsonism in everyday practice.